WorldWideScience

Sample records for syncytial virus induced

  1. Respiratory Syncytial Virus (RSV)

    Centers for Disease Control (CDC) Podcasts

    2013-02-04

    Respiratory Syncytial Virus, or RSV, causes cold-like symptoms but can be serious for infants and older adults. In this podcast, CDC’s Dr. Eileen Schneider discusses this common virus and offers tips to prevent its spread.  Created: 2/4/2013 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases (DVD).   Date Released: 2/13/2013.

  2. Learn about Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... Lung Health and Diseases > Lung Disease Lookup > RSV Learn About Respiratory Syncytial Virus (RSV) Respiratory syncytial virus ( ... file."); } }); } } --> Blank Section Header Lung Disease Lookup RSV Learn About Respiratory Syncytial Virus (RSV) RSV Symptoms, Causes & ...

  3. Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Olszewska, Wieslawa; Stryhn, Anette

    2004-01-01

    A CD8+ T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant Kd-restricted epitope from the viral transcription anti-terminator protein M2 (M2(82-90)), linked covalently to human beta2-microglobulin (beta2m). Cutaneous gene......-gun immunization of BALB/c mice with this construct induced an antigen-specific CD8+ T-cell memory. After intranasal RSV challenge, accelerated CD8+ T-cell responses were observed in pulmonary lymph nodes and virus clearance from the lungs was enhanced. The construct induced weaker CD8+ T-cell responses than those...... elicited with recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger than those induced by a similar DNA construct without the beta2m gene. DNA vaccination led to enhanced pulmonary disease after RSV challenge, with increased weight loss and cell recruitment to the lung. Depletion...

  4. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; van Heerde, Marc; Twisk, Jos W. R.; Plotz, Frans B.; Markhors, Dick G.

    2009-01-01

    Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  5. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneijber, M.C.J.; van Heerde, M.; Twisk, J.W.R.; Plotz, F.; Markhorst, D.G.

    2009-01-01

    Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  6. Sustained Protein Kinase D Activation Mediates Respiratory Syncytial Virus-Induced Airway Barrier Disruption

    OpenAIRE

    Rezaee, Fariba; DeSando, Samantha A.; Ivanov, Andrei I.; Chapman, Timothy J.; Knowlden, Sara A.; Beck, Lisa A.; Georas, Steve N.

    2013-01-01

    Understanding the regulation of airway epithelial barrier function is a new frontier in asthma and respiratory viral infections. Despite recent progress, little is known about how respiratory syncytial virus (RSV) acts at mucosal sites, and very little is known about its ability to influence airway epithelial barrier function. Here, we studied the effect of RSV infection on the airway epithelial barrier using model epithelia. 16HBE14o- bronchial epithelial cells were grown on Transwell insert...

  7. Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

    Science.gov (United States)

    Leemans, A; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M L; Melero, J A; McLellan, J S; Graham, B S; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P

    2017-07-15

    Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are

  8. Respiratory Syncytial Virus Promotes Moraxella catarrhalis-Induced Ascending Experimental Otitis Media

    Science.gov (United States)

    Brockson, M. Elizabeth; Novotny, Laura A.; Jurcisek, Joseph A.; McGillivary, Glen; Bowers, Martha R.; Bakaletz, Lauren O.

    2012-01-01

    Otitis media (OM) is a polymicrobial disease wherein prior or concurrent infection with an upper respiratory tract virus plays an essential role, predisposing the middle ear to bacterial invasion. In episodes of acute bacterial OM, respiratory syncytial virus (RSV) is the most commonly isolated virus and thus serves as an important co-pathogen. Of the predominant bacterial agents of OM, the pathogenesis of disease due to Moraxella catarrhalis is the least well understood. Rigorous study of M. catarrhalis in the context of OM has been significantly hindered by lack of an animal model. To bridge this gap, we assessed whether co-infection of chinchillas with M. catarrhalis and RSV would facilitate ascension of M. catarrhalis from the nasopharynx into the middle ear. Chinchillas were challenged intranasally with M. catarrhalis followed 48 hours later by intranasal challenge with RSV. Within 7 days, 100% of nasopharynges were colonized with M. catarrhalis and homogenates of middle ear mucosa were also culture-positive. Moreover, within the middle ear space, the mucosa exhibited hemorrhagic foci, and a small volume of serosanguinous effusion was present in one of six ears. To improve upon this model, and based on epidemiologic data, nontypeable Haemophilus influenzae (NTHI) was included as an additional bacterial co-pathogen via intranasal administration four days before M. catarrhalis challenge. With this latter protocol, M. catarrhalis was cultured from the nasopharynx and middle ear homogenates of a maximum of 88% and 79% animals, respectively, for up to 17 days after intranasal challenge with M. catarrhalis. Additionally, hemorrhagic foci were observed in 79% of middle ears upon sacrifice. Thus, these data demonstrated that co-infection with RSV and NTHI predisposed to M. catarrhalis-induced ascending experimental OM. This model can be used both in studies of pathogenesis as well as to investigate strategies to prevent or treat OM due to M. catarrhalis. PMID:22768228

  9. Respiratory syncytial virus promotes Moraxella catarrhalis-induced ascending experimental otitis media.

    Directory of Open Access Journals (Sweden)

    M Elizabeth Brockson

    Full Text Available Otitis media (OM is a polymicrobial disease wherein prior or concurrent infection with an upper respiratory tract virus plays an essential role, predisposing the middle ear to bacterial invasion. In episodes of acute bacterial OM, respiratory syncytial virus (RSV is the most commonly isolated virus and thus serves as an important co-pathogen. Of the predominant bacterial agents of OM, the pathogenesis of disease due to Moraxella catarrhalis is the least well understood. Rigorous study of M. catarrhalis in the context of OM has been significantly hindered by lack of an animal model. To bridge this gap, we assessed whether co-infection of chinchillas with M. catarrhalis and RSV would facilitate ascension of M. catarrhalis from the nasopharynx into the middle ear. Chinchillas were challenged intranasally with M. catarrhalis followed 48 hours later by intranasal challenge with RSV. Within 7 days, 100% of nasopharynges were colonized with M. catarrhalis and homogenates of middle ear mucosa were also culture-positive. Moreover, within the middle ear space, the mucosa exhibited hemorrhagic foci, and a small volume of serosanguinous effusion was present in one of six ears. To improve upon this model, and based on epidemiologic data, nontypeable Haemophilus influenzae (NTHI was included as an additional bacterial co-pathogen via intranasal administration four days before M. catarrhalis challenge. With this latter protocol, M. catarrhalis was cultured from the nasopharynx and middle ear homogenates of a maximum of 88% and 79% animals, respectively, for up to 17 days after intranasal challenge with M. catarrhalis. Additionally, hemorrhagic foci were observed in 79% of middle ears upon sacrifice. Thus, these data demonstrated that co-infection with RSV and NTHI predisposed to M. catarrhalis-induced ascending experimental OM. This model can be used both in studies of pathogenesis as well as to investigate strategies to prevent or treat OM due to M

  10. Apnea induced by respiratory syncytial virus infection is not associated with viral invasion of the central nervous system.

    Science.gov (United States)

    Erez, Daniella Levy; Yarden-Bilavsky, Havatzelet; Mendelson, Ella; Yuhas, Yael; Ashkenazi, Shai; Nahum, Elhanan; Berent, Eva; Hindiyeh, Musa; Bilavsky, Efraim

    2014-08-01

    We aimed to study whether direct central nervous system invasion is responsible for the neurologic manifestations seen in hospitalized infants with respiratory syncytial virus (RSV) infection. Cerebrospinal fluid from infants with RSV infection was tested for the detection of the following respiratory RNA viruses: RSV, influenza A and B, pandemic influenza H1N1, Parainfluenza-3, human metapneumovirus, adenovirus, parechovirus and enterovirus. All children tested negative for the presence of viral material in the cerebrospinal fluid. Our results support the notion that the mechanism of RSV-induced neurologic manifestations, including apnea, is not direct central nervous system invasion.

  11. Sustained protein kinase D activation mediates respiratory syncytial virus-induced airway barrier disruption.

    Science.gov (United States)

    Rezaee, Fariba; DeSando, Samantha A; Ivanov, Andrei I; Chapman, Timothy J; Knowlden, Sara A; Beck, Lisa A; Georas, Steve N

    2013-10-01

    Understanding the regulation of airway epithelial barrier function is a new frontier in asthma and respiratory viral infections. Despite recent progress, little is known about how respiratory syncytial virus (RSV) acts at mucosal sites, and very little is known about its ability to influence airway epithelial barrier function. Here, we studied the effect of RSV infection on the airway epithelial barrier using model epithelia. 16HBE14o- bronchial epithelial cells were grown on Transwell inserts and infected with RSV strain A2. We analyzed (i) epithelial apical junction complex (AJC) function, measuring transepithelial electrical resistance (TEER) and permeability to fluorescein isothiocyanate (FITC)-conjugated dextran, and (ii) AJC structure using immunofluorescent staining. Cells were pretreated or not with protein kinase D (PKD) inhibitors. UV-irradiated RSV served as a negative control. RSV infection led to a significant reduction in TEER and increase in permeability. Additionally it caused disruption of the AJC and remodeling of the apical actin cytoskeleton. Pretreatment with two structurally unrelated PKD inhibitors markedly attenuated RSV-induced effects. RSV induced phosphorylation of the actin binding protein cortactin in a PKD-dependent manner. UV-inactivated RSV had no effect on AJC function or structure. Our results suggest that RSV-induced airway epithelial barrier disruption involves PKD-dependent actin cytoskeletal remodeling, possibly dependent on cortactin activation. Defining the mechanisms by which RSV disrupts epithelial structure and function should enhance our understanding of the association between respiratory viral infections, airway inflammation, and allergen sensitization. Impaired barrier function may open a potential new therapeutic target for RSV-mediated lung diseases.

  12. A highly attenuated recombinant human respiratory syncytial virus lacking the G protein induces long-lasting protection in cotton rats

    Directory of Open Access Journals (Sweden)

    van Remmerden Yvonne

    2010-06-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (rRSV and an rRSV lacking the G gene (ΔG were constructed based on a clinical RSV isolate (strain 98-25147-X. Results Growth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for ΔG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days. Conclusion Collectively, the data indicate that a single dose immunization with the highly attenuated ΔG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since ΔG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.

  13. Gold nanorod vaccine for respiratory syncytial virus

    International Nuclear Information System (INIS)

    Stone, John W; Thornburg, Natalie J; Blum, David L; Kuhn, Sam J; Crowe Jr, James E; Wright, David W

    2013-01-01

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response. (paper)

  14. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure.

    Science.gov (United States)

    Kneyber, Martin C J; van Heerde, Marc; Twisk, Jos W R; Plötz, Frans B; Markhors, Dick G

    2009-01-01

    Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal. Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval. Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol. Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468).

  15. Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice

    Science.gov (United States)

    Foronjy, Robert F.; Dabo, Abdoulaye J.; Taggart, Clifford C.; Weldon, Sinead; Geraghty, Patrick

    2014-01-01

    Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression. PMID:24587397

  16. Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein.

    Directory of Open Access Journals (Sweden)

    Ah-Ra Kim

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of lower respiratory tract illness in infants, young children and the elderly. However, there is no licensed vaccine available against RSV infection. In this study, we generated virus-like particle (VLP vaccine and investigated the vaccine efficacy in a mouse model. For VLP vaccines, tandem gene (1-780 bp for V1 VLPs and tandem repeat gene (repeated 450-780 bp for V5 VLPs were constructed in pFastBacTM vectors, respectively. Influenza matrix protein 1 (M1 was used as a core protein in the VLPs. Notably, upon challenge infection, significantly lower virus loads were measured in the lung of mice immunized with V1 or V5 VLPs compared to those of naïve mice and formalin-inactivated RSV immunized control mice. In particular, V5 VLPs immunization showed significantly lower virus titers than V1 VLPs immunization. Furthermore, V5 VLPs immunization elicited increased memory B cells responses in the spleen. These results indicated that V5 VLP vaccine containing tandem repeat gene protein provided better protection than V1 VLPs with significantly decreased inflammation in the lungs. Thus, V5 VLPs could be a potential vaccine candidate against RSV.

  17. Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats.

    Directory of Open Access Journals (Sweden)

    Gale Smith

    Full Text Available Respiratory Syncytial Virus (RSV is an important viral agent causing severe respiratory tract disease in infants and children as well as in the elderly and immunocompromised individuals. The lack of a safe and effective RSV vaccine represents a major unmet medical need. RSV fusion (F surface glycoprotein was modified and cloned into a baculovirus vector for efficient expression in Sf9 insect cells. Recombinant RSV F was glycosylated and cleaved into covalently linked F2 and F1 polypeptides that formed homotrimers. RSV F extracted and purified from insect cell membranes assembled into 40 nm protein nanoparticles composed of multiple RSV F oligomers arranged in the form of rosettes. The immunogenicity and protective efficacy of purified RSV F nanoparticles was compared to live and formalin inactivated RSV in cotton rats. Immunized animals induced neutralizing serum antibodies, inhibited virus replication in the lungs, and had no signs of disease enhancement in the respiratory track of challenged animals. RSV F nanoparticles also induced IgG competitive for binding of palivizumab neutralizing monoclonal antibody to RSV F antigenic site II. Antibodies to this epitope are known to protect against RSV when passively administered in high risk infants. Together these data provide a rational for continued development a recombinant RSV F nanoparticle vaccine candidate.

  18. Bovine respiratory syncytial virus (BRSV): A review

    DEFF Research Database (Denmark)

    Larsen, Lars Erik

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) infection is the major cause of respiratory disease in calves during the first year of life. The study of the virus has been difficult because of its lability and very poor growth in cell culture. However, during the last decade, the introduction of new...... complex and unpredictable which makes the diagnosis and subsequent therapy very difficult. BRSV is closely related to human respiratory syncytial virus (HRSV) which is an important cause of respiratory disease in young children. In contrast to BRSV, the recent knowledge of HRSV is regularly extensively...

  19. Nucleic acids of respiratory syncytial virus.

    OpenAIRE

    Lambert, D M; Pons, M W; Mbuy, G N; Dorsch-Hasler, K

    1980-01-01

    Analysis of purified respiratory syncytial virus revealed that the virion RNA was composed of 50S, 28S, 18S, and 4S species. The 18S and 28S species were presumed to represent host rRNA since virus grown in actinomycin D-treated cells contained only 50S and 4S RNAs. Actinomycin D treatment stimulated production of infectious respiratory syncytial virus 5- to 10-fold. The 50S virion RNA was shown to hybridize with polyadenylated mRNA's isolated from infected cells, indicating that respiratory ...

  20. Human Respiratory Syncytial Virus and Human Metapneumovirus

    OpenAIRE

    Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns

    2009-01-01

    The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...

  1. BIOLOGY OF HUMAN RESPIRATORY SYNCYTIAL VIRUS: A ...

    African Journals Online (AJOL)

    DR. AMINU

    information about its biology which may be useful to the present and future researchers. Key words: Respiratory virus, Human Respiratory syncytial virus, biology, genome, epidemiology, immunity. INTRODUCTION. Acute lower ..... of respiratory infections in bone marrow transplant. Pneumonia develops in about one-half of ...

  2. Respiratory syncytial virus-induced acute and chronic airway disease is independent of genetic background: An experimental murine model

    Directory of Open Access Journals (Sweden)

    Ramilo Octavio

    2005-05-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the leading respiratory viral pathogen in young children worldwide. RSV disease is associated with acute airway obstruction (AO, long-term airway hyperresponsiveness (AHR, and chronic lung inflammation. Using two different mouse strains, this study was designed to determine whether RSV disease patterns are host-dependent. C57BL/6 and BALB/c mice were inoculated with RSV and followed for 77 days. RSV loads were measured by plaque assay and polymerase chain reaction (PCR in bronchoalveolar lavage (BAL and whole lung samples; cytokines were measured in BAL samples. Lung inflammation was evaluated with a histopathologic score (HPS, and AO and AHR were determined by plethysmography. Results Viral load dynamics, histopathologic score (HPS, cytokine concentrations, AO and long-term AHR were similar in both strains of RSV-infected mice, although RSV-infected C57BL/6 mice developed significantly greater AO compared with RSV-infected BALB/c mice on day 5. PCR detected RSV RNA in BAL samples of RSV infected mice until day 42, and in whole lung samples through day 77. BAL concentrations of cytokines TNF-α, IFN-γ, and chemokines MIG, RANTES and MIP-1α were significantly elevated in both strains of RSV-infected mice compared with their respective controls. Viral load measured by PCR significantly correlated with disease severity on days 14 and 21. Conclusion RSV-induced acute and chronic airway disease is independent of genetic background.

  3. Coptidis Rhizoma extract inhibits replication of respiratory syncytial virus in vitro and in vivo by inducing antiviral state.

    Science.gov (United States)

    Lee, Byeong-Hoon; Chathuranga, Kiramage; Uddin, Md Bashir; Weeratunga, Prasanna; Kim, Myun Soo; Cho, Won-Kyung; Kim, Hong Ik; Ma, Jin Yeul; Lee, Jong-Soo

    2017-06-01

    Coptidis Rhizoma is derived from the dried rhizome of Ranunculaceous plants and is a commonly used traditional Chinese medicine. Although Coptidis Rhizoma is commonly used for its many therapeutic effects, antiviral activity against respiratory syncytial virus (RSV) has not been reported in detail. In this study, we evaluated the antiviral activities of Coptidis Rhizoma extract (CRE) against RSV in human respiratory tract cell line (HEp2) and BALB/c mice. An effective dose of CRE significantly reduces the replication of RSV in HEp2 cells and reduces the RSV-induced cell death. This antiviral activity against RSV was through the induction of type I interferon-related signaling and the antiviral state in HEp2 cells. More importantly, oral administration of CRE exhibited prophylactic effects in BALB/c mice against RSV. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we confirmed that palmatine was related to the antiviral properties and immunemodulation effect. Taken together, an extract of Coptidis Rhizoma and its components play roles as immunomodulators and could be a potential source as promising natural antivirals that can confer protection to RSV. These outcomes should encourage further allied studies in other natural products.

  4. Double-stranded RNA induces similar pulmonary dysfunction to respiratory syncytial virus in BALB/c mice.

    Science.gov (United States)

    Aeffner, Famke; Traylor, Zachary P; Yu, Erin N Z; Davis, Ian C

    2011-07-01

    Both respiratory syncytial virus (RSV) and influenza A virus induce nucleotide/P2Y purinergic receptor-mediated impairment of alveolar fluid clearance (AFC), which contributes to formation of lung edema. Although genetically dissimilar, both viruses generate double-stranded RNA replication intermediates, which act as Toll-like receptor (TLR)-3 ligands. We hypothesized that double-stranded RNA/TLR-3 signaling underlies nucleotide-mediated inhibition of amiloride-sensitive AFC in both infections. We found that addition of the synthetic double-stranded RNA analog poly-inosinic-cytidylic acid [poly(I:C)] (500 ng/ml) to the AFC instillate resulted in nucleotide/P2Y purinergic receptor-mediated inhibition of amiloride-sensitive AFC in BALB/c mice but had no effect on cystic fibrosis transmembrane regulator (CFTR)-mediated Cl(-) transport. Poly(I:C) also induced acute keratinocyte cytokine-mediated AFC insensitivity to stimulation by the β-adrenergic agonist terbutaline. Inhibitory effects of poly(I:C) on AFC were absent in TLR-3(-/-) mice and were not replicated by addition to the AFC instillate of ligands for other TLRs except TLR-2. Intranasal poly(I:C) administration (250 μg/mouse) similarly induced nucleotide-dependent AFC inhibition 2-3 days later, together with increased lung water content and neutrophilic inflammation. Intranasal treatment of BALB/c mice with poly(I:C) did not induce airway hyperresponsiveness at day 2 but did result in insensitivity to airway bronchodilation by β-adrenergic agonists. These findings suggest that viral double-stranded RNA replication intermediates induce nucleotide-mediated impairment of amiloride-sensitive AFC in both infections, together with β-adrenergic agonist insensitivity. Both of these effects also occur in RSV infection. However, double-stranded RNA replication intermediates do not appear to be sufficient to induce either adenosine-mediated, CFTR-dependent Cl(-) secretion in the lung or severe, lethal hypoxemia, both

  5. The respiratory syncytial virus G protein conserved domain induces a persistent and protective antibody response in rodents.

    Directory of Open Access Journals (Sweden)

    Thien N Nguyen

    Full Text Available Respiratory syncytial virus (RSV is an important cause of severe upper and lower respiratory disease in infants and in the elderly. There are 2 main RSV subtypes A and B. A recombinant vaccine was designed based on the central domain of the RSV-A attachment G protein which we had previously named G2Na (aa130-230. Here we evaluated immunogenicity, persistence of antibody (Ab response and protective efficacy induced in rodents by: (i G2Na fused to DT (Diphtheria toxin fragments in cotton rats. DT fusion did not potentiate neutralizing Ab responses against RSV-A or cross-reactivity to RSV-B. (ii G2Nb (aa130-230 of the RSV-B G protein either fused to, or admixed with G2Na. G2Nb did not induce RSV-B-reactive Ab responses. (iii G2Na at low doses. Two injections of 3 µg G2Na in Alum were sufficient to induce protective immune responses in mouse lungs, preventing RSV-A and greatly reducing RSV-B infections. In cotton rats, G2Na-induced RSV-reactive Ab and protective immunity against RSV-A challenge that persisted for at least 24 weeks. (iv injecting RSV primed mice with a single dose of G2Na/Alum or G2Na/PLGA [poly(D,L-lactide-co-glycolide]. Despite the presence of pre-existing RSV-specific Abs, these formulations effectively boosted anti-RSV Ab titres and increased Ab titres persisted for at least 21 weeks. Affinity maturation of these Abs increased from day 28 to day 148. These data indicate that G2Na has potential as a component of an RSV vaccine formulation.

  6. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  7. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    International Nuclear Information System (INIS)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-01-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  8. Human Respiratory Syncytial Virus and Human Metapneumovirus

    Directory of Open Access Journals (Sweden)

    Luciana Helena Antoniassi da Silva

    2009-08-01

    Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms.  The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.

  9. A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease.

    Science.gov (United States)

    Wiegand, Marian Alexander; Gori-Savellini, Gianni; Gandolfo, Claudia; Papa, Guido; Kaufmann, Christine; Felder, Eva; Ginori, Alessandro; Disanto, Maria Giulia; Spina, Donatella; Cusi, Maria Grazia

    2017-05-15

    Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity

  10. A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.

    Science.gov (United States)

    Jiao, Yue-Ying; Fu, Yuan-Hui; Yan, Yi-Fei; Hua, Ying; Ma, Yao; Zhang, Xiu-Juan; Song, Jing-Dong; Peng, Xiang-Lei; Huang, Jiaqiang; Hong, Tao; He, Jin-Sheng

    2017-08-01

    Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully. The resulting VLPs showed similar immunoreactivity and function to RSV virion in vitro. Moreover, Th1 polarized response, and effective mucosal virus-neutralizing antibody and CD8 + T-cell responses were induced by a single intranasal (i.n.) administration of RSV VLPs rather than intramuscular (i.m.) inoculation, although the comparable RSV F-specific serum IgG and long-lasting RSV-specific neutralizing antibody were detected in the mice immunized by both routes. Upon RSV challenge, VLP-immunized mice showed increased viral clearance but decreased signs of enhanced lung pathology and fewer eosinophils compared to mice immunized with formalin-inactivated RSV (FI-RSV). In addition, a single i.n. RSV VLP vaccine has the capability to induce RSV-specific long-lasting neutralizing antibody responses observable up to 15 months. Our results demonstrate that the long-term and memory immune responses in mice against RSV were induced by a single i.n. administration of RSV VLP vaccine, suggesting a successful approach of RSV VLPs as an effective and safe mucosal vaccine against RSV infection, and an applicable and qualified platform of FGAd-infected Vero cells for VLP production. Copyright © 2017. Published by Elsevier B.V.

  11. Biology of human respiratory syncytial virus: a review | Aliyu | Bayero ...

    African Journals Online (AJOL)

    Acute lower respiratory tract infection is one of the major causes of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) is the single most important viral cause of lower respiratory tract infection during infancy and early childhood worldwide. Respiratory syncytial virus belongs to the ...

  12. Respiratory syncytial virus bronchiolitis and hypertransaminasemia.

    Science.gov (United States)

    Giordano, Salvatore; Di Gangi, Maria; Failla, Maria Concetta; Bruno, Lucrezia; Falcone, Veronica; Dones, Piera

    2018-03-01

    Bronchiolitis is the most common disease of the lower respiratory tract occurring in children during their first year of life, becoming the most frequent cause of hospitalization. Although the disease can also be caused by other viruses, more than 70% of bronchiolitis cases are caused by respiratory syncytial virus (RSV). RSV bronchiolitis clinically presents rhinitis, coughing, increased breathing and eating difficulties; the symptoms are usually mild, but in some cases may be so severe as to require hospitalization. Diagnosis is mainly clinical and is based on a thorough medical history and a physical examination. Therapy is substantially of support, and has the aim of ensuring alimentation/hydration and optimal oxygenation. It has been recently noted that RSV infections may cause extra-pulmonary manifestations, including liver problems, as rarely described in the literature. The aim of this paper is to present three cases of RSV bronchiolitis in children with elevated transitory transaminase levels.

  13. Live-Attenuated Respiratory Syncytial Virus Vaccines

    Science.gov (United States)

    Buchholz, Ursula J.; Collins, Peter L.

    2016-01-01

    Live-attenuated respiratory syncytial virus (RSV) vaccines offer several advantages for immunization of infants and young children: (1) they do not cause vaccine-associated enhanced RSV disease; (2) they broadly stimulate innate, humoral, and cellular immunity, both systemically and locally in the respiratory tract; (3) they are delivered intranasally; and (4) they replicate in the upper respiratory tract of young infants despite the presence of passively acquired maternally derived RSV neutralizing antibody. This chapter describes early efforts to develop vaccines through the classic methods of serial cold-passage and chemical mutagenesis, and recent efforts using reverse genetics to derive attenuated derivatives of wild-type (WT) RSV and to develop parainfluenza vaccine vectors that express RSV surface glycoproteins. PMID:24362694

  14. Need for a safe vaccine against respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Joo-Young Kim

    2012-09-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.

  15. Vaccine Induced Herd Immunity for Control of Respiratory Syncytial Virus Disease in a Low-Income Country Setting.

    Science.gov (United States)

    Kinyanjui, Timothy M; House, Thomas A; Kiti, Moses C; Cane, Patricia A; Nokes, David J; Medley, Graham F

    2015-01-01

    Respiratory syncytial virus (RSV) is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6 m). Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV. We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5-10 m) is likely to be a highly effective method of protection of infants (herd immunity). A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters. This result suggests that vaccinating older infants and children against RSV can have a major public health benefit.

  16. Vaccine Induced Herd Immunity for Control of Respiratory Syncytial Virus Disease in a Low-Income Country Setting.

    Directory of Open Access Journals (Sweden)

    Timothy M Kinyanjui

    Full Text Available Respiratory syncytial virus (RSV is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6 m. Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV.We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5-10 m is likely to be a highly effective method of protection of infants (<6 m against hospitalisation. The majority benefit is derived from indirect protection (herd immunity. A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters.This result suggests that vaccinating older infants and children against RSV can have a major public health benefit.

  17. Respiratory syncytial virus and innate immunity: a complex interplay of exploitation and subversion.

    Science.gov (United States)

    Johnson, Teresa R

    2006-06-01

    Respiratory syncytial virus causes significant disease in infants, the elderly and select groups of immunocompromised patients. Healthy individuals are also naturally infected with respiratory syncytial virus repeatedly throughout life. Therefore, safe and effective vaccines and therapies are needed. However, a number of factors have prevented development of such antiviral interventions to date. These include a failed vaccine trial, the very young age of the primary target population (neonates), the inability of natural infection to induce long-term protective immunity, and an incomplete understanding of virus-host interactions. The identification of pattern recognition receptors has led to significant increases in our understanding of induction and regulation of innate immune responses. This review will address the impact of these findings on respiratory syncytial virus research.

  18. Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection.

    Science.gov (United States)

    Tomosada, Yohsuke; Chiba, Eriko; Zelaya, Hortensia; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio

    2013-08-15

    Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. The aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. Nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible

  19. Validation of a pediatric caregiver diary to measure symptoms of postacute respiratory syncytial virus bronchiolitis

    DEFF Research Database (Denmark)

    Santanello, Nancy C; Norquist, Josephine M; Nelsen, Linda M

    2005-01-01

    Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated with continuing respiratory symptoms following hospitalization. To date, there is no validated objective measure to evaluate symptoms of RSV-induced bronchiolitis. We report on the reliability, validity, and respons...

  20. Hot topics in the prevention of respiratory syncytial virus disease.

    Science.gov (United States)

    Habibi, Maximillian S; Patel, Sanjay; Openshaw, Peter

    2011-03-01

    The 7th International Respiratory Syncytial Virus Symposium took place in Hotel Blijdorp, Rotterdam, The Netherlands. The series has been running since 1996; this meeting took place after a 3-year gap, and was attended by approximately 200 clinicians, scientists and industry representatives from all over the world. The conference covered all aspects of respiratory syncytial virus disease, including virology, cell biology, pathogenesis, clinical presentation, diagnosis, immunology, vaccines, antivirals and other therapeutic approaches. Reviews by invited keynote speakers were accompanied by oral and poster presentations, with ample opportunity for discussion of unpublished work. This article summarizes a small selection of hot topics from the meeting, focused on pathogenesis, therapeutics and vaccine development.

  1. Invasive pneumococcal and meningococcal disease : association with influenza virus and respiratory syncytial virus activity?

    NARCIS (Netherlands)

    Jansen, A G S C; Sanders, E A M; VAN DER Ende, A; VAN Loon, A M; Hoes, A W; Hak, E

    2008-01-01

    Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and

  2. Simultaneous detection of respiratory syncytial virus types A and B ...

    African Journals Online (AJOL)

    Tharwat Ezzat Deraz

    2012-02-28

    Feb 28, 2012 ... Abstract Background: Respiratory syncytial virus (RSV) types A and B and influenza A and B cause about 80–90% of viral lower respiratory tract infections. It is impossible to distinguish the cause of viral respiratory infections by their clinical presentation. Multiplex RT-PCR has a signif- icant advantage in ...

  3. Simultaneous detection of respiratory syncytial virus types A and B ...

    African Journals Online (AJOL)

    Background: Respiratory syncytial virus (RSV) types A and B and influenza A and B cause about 80–90% of viral lower respiratory tract infections. It is impossible to distinguish the cause of viral respiratory infections by their clinical presentation. Multiplex RT-PCR has a significant advantage in that it permits the ...

  4. 21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

    Science.gov (United States)

    2010-04-01

    .... 866.3480 Section 866.3480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to respiratory syncytial virus in serum. Additionally, some of these reagents consist of respiratory...

  5. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease...

  6. Influenza- and respiratory syncytial virus-associated adult mortality ...

    African Journals Online (AJOL)

    Background. Influenza and respiratory syncytial virus (RSV) infections cause seasonal excess mortality and hospitalisation in adults (particularly the elderly) in high-income countries. Little information exists on the impact of these infections on adults in Africa. Objectives. To estimate influenza- and RSV-related adult mortality ...

  7. Human Metapneumovirus and Respiratory Syncytial Virus Disease in Children, Yemen

    Science.gov (United States)

    Al-Sonboli, Najla; Hart, Charles A.; Al-Aghbari, Nasher; Al-Ansi, Ahmed; Ashoor, Omar

    2006-01-01

    Factors increasing the severity of respiratory infections in developing countries are poorly described. We report factors associated with severe acute respiratory illness in Yemeni children (266 infected with respiratory syncytial virus and 66 with human metapneumovirus). Age, indoor air pollution, and incomplete vaccinations were risk factors and differed from those in industrialized countries. PMID:17073098

  8. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  9. The epidemiology of respiratory syncytial virus (RSV) infections in ...

    African Journals Online (AJOL)

    Objectives. To review the incidence, outcomes and risk factors associated with respiratory syncytial virus (RSV) infection in South African children. Design. Review of published literature and laboratory records. Methods. Review of the published literature. Articles listed on MEDLINE with 'South African' or 'children' and ...

  10. Wheeze after Hospitalization for Respiratory Syncytial Virus Infection in Children

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Simonsen, Jacob; Breindahl, Morten

    2018-01-01

    Introduction Prior studies found associations between respiratory syncytial virus (RSV) infection, wheezing, and asthma. The present study aimed to examine the risk of wheezing after RSV, by the history of wheezing. Methods We included 39 children hospitalized for RSV infection (cases) and 23...... children hospitalized for nonrespiratory tract infection reasons (controls) and followed the children prospectively with regular standardized telephone interviews until 18 months, and again 5 years after inclusion. The risk of wheeze was estimated by odds ratios (OR), comparing children hospitalized...

  11. Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Abdoulaye J Dabo

    Full Text Available Increased lung levels of matrix metalloproteinase 9 (MMP9 are frequently observed during respiratory syncytial virus (RSV infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9's role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR.

  12. Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite vaccination

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tegtmeier, C.; Pedersen, E.

    2001-01-01

    The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the o......The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior...... that the vaccine induced only sparse levels of antibodies probably due to the presence of maternally derived antibodies at the time of vaccination. Necropsy findings in 5 calves revealed changes typical for infectious pneumonia with involvment of BRSV. In conclusion, vaccination of calves against BRSV in 2 Danish...

  13. Replication and clearance of respiratory syncytial virus - Apoptosis is an important pathway of virus clearance after experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Viuff, B.; Tjørnehøj, Kirsten; Larsen, Lars Erik

    2002-01-01

    and the infections with human respiratory syncytial. virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication...... and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared...

  14. Comparison of direct and indirect immunofluorescence staining of clinical specimens for detection of respiratory syncytial virus antigen.

    OpenAIRE

    Minnich, L L; Ray, C G

    1982-01-01

    Immunofluorescence staining methods for respiratory syncytial virus antigen detection were compared. Of 50 specimens originally positive for respiratory syncytial virus by direct immunofluorescence and culture, 49 were positive by repeat direct immunofluorescence and 32 were positive by indirect immunofluorescence. Additional results obtained on specimens originally negative for respiratory syncytial virus by direct immunofluorescence, culture, or both indicate that direct immunofluorescence ...

  15. Packaging and Prefusion Stabilization Separately and Additively Increase the Quantity and Quality of Respiratory Syncytial Virus (RSV)-Neutralizing Antibodies Induced by an RSV Fusion Protein Expressed by a Parainfluenza Virus Vector.

    Science.gov (United States)

    Liang, Bo; Ngwuta, Joan O; Herbert, Richard; Swerczek, Joanna; Dorward, David W; Amaro-Carambot, Emerito; Mackow, Natalie; Kabatova, Barbora; Lingemann, Matthias; Surman, Sonja; Yang, Lijuan; Chen, Man; Moin, Syed M; Kumar, Azad; McLellan, Jason S; Kwong, Peter D; Graham, Barney S; Schaap-Nutt, Anne; Collins, Peter L; Munir, Shirin

    2016-11-01

    Human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are major pediatric respiratory pathogens that lack vaccines. A chimeric bovine/human PIV3 (rB/HPIV3) virus expressing the unmodified, wild-type (wt) RSV fusion (F) protein from an added gene was previously evaluated in seronegative children as a bivalent intranasal RSV/HPIV3 vaccine, and it was well tolerated but insufficiently immunogenic for RSV F. We recently showed that rB/HPIV3 expressing a partially stabilized prefusion form (pre-F) of RSV F efficiently induced "high-quality" RSV-neutralizing antibodies, defined as antibodies that neutralize RSV in vitro without added complement (B. Liang et al., J Virol 89:9499-9510, 2015, doi:10.1128/JVI.01373-15). In the present study, we modified RSV F by replacing its cytoplasmic tail (CT) domain or its CT and transmembrane (TM) domains (TMCT) with counterparts from BPIV3 F, with or without pre-F stabilization. This resulted in RSV F being packaged in the rB/HPIV3 particle with an efficiency similar to that of RSV particles. Enhanced packaging was substantially attenuating in hamsters (10- to 100-fold) and rhesus monkeys (100- to 1,000-fold). Nonetheless, TMCT-directed packaging substantially increased the titers of high-quality RSV-neutralizing serum antibodies in hamsters. In rhesus monkeys, a strongly additive immunogenic effect of packaging and pre-F stabilization was observed, as demonstrated by 8- and 30-fold increases of RSV-neutralizing serum antibody titers in the presence and absence of added complement, respectively, compared to pre-F stabilization alone. Analysis of vaccine-induced F-specific antibodies by binding assays indicated that packaging conferred substantial stabilization of RSV F in the pre-F conformation. This provides an improved version of this well-tolerated RSV/HPIV3 vaccine candidate, with potently improved immunogenicity, which can be returned to clinical trials. Human respiratory syncytial virus (RSV) and

  16. Antibody responses against epitopes on the F protein of bovine respiratory syncytial virus differ in infected or vaccinated cattle

    NARCIS (Netherlands)

    Schrijver, R.S.; Hensen, E.J.; Langedijk, J.P.M.; Daus, F.; Middel, W.G.J.; Kramps, J.A.; Oirschot, van J.T.

    1997-01-01

    The fusion protein F of bovine respiratory syncytial virus (BRSV) is an important target for humoral and cellular immune responses, and antibodies against the F protein have been associated with protection. However, the F protein can induce antibodies with different biological activity, possibly

  17. Secretory Expression and Purification of Respiratory Syncytial Virus G and F Proteins in Human Cells.

    Science.gov (United States)

    Jadhao, Samadhan J; Anderson, Larry J

    2016-01-01

    Respiratory syncytial virus (RSV) is one of the leading causes of range of symptoms from mild upper to serious lower respiratory virus infections in infants, immunocompromised individuals, and the elderly. Despite many decades of research and development, a licensed RSV vaccine is not available for use in human. Since the RSV F and G proteins induce neutralizing antibodies and confer protection from infection, they are important for understanding disease and for developing vaccines and access to purified, expressed proteins is important to RSV research and diagnostics. We describe methods to produce recombinant RSV F and G proteins in human cells and purify these proteins using Ni Sepharose affinity chromatography.

  18. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus

    NARCIS (Netherlands)

    Gaunt, Eleanor R.; Jansen, Rogier R.; Poovorawan, Yong; Templeton, Kate E.; Toms, Geoffrey L.; Simmonds, Peter

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  19. Molecular Epidemiology and Evolution of Human Respiratory Syncytial Virus and Human Metapneumovirus

    NARCIS (Netherlands)

    Gaunt, E.R.; Jansen, R.R.; Poovorawan, Y.; Templeton, K.E.; Toms, G.L.; Simmonds, P.

    2011-01-01

    Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse

  20. Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice

    NARCIS (Netherlands)

    Barends, M.; de Rond, L. G. H.; Dormans, J.; van Oosten, M.; Boelen, A.; Neijens, H. J.; Osterhaus, A. D. M. E.; Kimman, T. G.

    2004-01-01

    Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response,

  1. Increased concordance of severe respiratory syncytial virus infection in identical twins

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; Stensballe, Lone Graff; Skytthe, Axel

    2008-01-01

    in Denmark between 1994 and 2003. Latent-factor models of genetic and environmental effects were fitted to the observed data by using maximal likelihood methods. RESULTS: Identical twins resembled each other significantly more than did fraternal twins for respiratory syncytial virus hospitalization......OBJECTIVE: We estimated differences in the severity of respiratory syncytial virus infection attributable to genetic and environmental factors. METHODS: Record linkage data on hospitalizations attributable to respiratory syncytial virus infection were gathered on all twins (12,346 pairs) born...

  2. Epidemiology, Molecular Epidemiology and Evolution of Bovine Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Gilberto Vaughan

    2012-11-01

    Full Text Available The bovine respiratory syncytial virus (BRSV is an enveloped, negative sense, single-stranded RNA virus belonging to the pneumovirus genus within the family Paramyxoviridae. BRSV has been recognized as a major cause of respiratory disease in young calves since the early 1970s. The analysis of BRSV infection was originally hampered by its characteristic lability and poor growth in vitro. However, the advent of numerous immunological and molecular methods has facilitated the study of BRSV enormously. The knowledge gained from these studies has also provided the opportunity to develop safe, stable, attenuated virus vaccine candidates. Nonetheless, many aspects of the epidemiology, molecular epidemiology and evolution of the virus are still not fully understood. The natural course of infection is rather complex and further complicates diagnosis, treatment and the implementation of preventive measures aimed to control the disease. Therefore, understanding the mechanisms by which BRSV is able to establish infection is needed to prevent viral and disease spread. This review discusses important information regarding the epidemiology and molecular epidemiology of BRSV worldwide, and it highlights the importance of viral evolution in virus transmission.

  3. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial

    DEFF Research Database (Denmark)

    Carbonell-Estrany, Xavier; Simões, Eric A F; Dagan, Ron

    2009-01-01

    OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, ...

  4. Respiratory Syncytial Virus (RSV) Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... children-s-health-issues/viral-infections-in-infants-and-children/respiratory-syncytial-virus-rsv-infection-and-human-metapneumovirus-infection National Cancer Institute [Internet]. Bethesda (MD): U.S. Department of Health and Human ...

  5. Causal direction between respiratory syncytial virus bronchiolitis and asthma studied in monozygotic twins

    DEFF Research Database (Denmark)

    Poorisrisak, Porntiva; Halkjaer, Liselotte Brydensholt; Thomsen, Simon Francis

    2010-01-01

    Respiratory syncytial virus (RSV) bronchiolitis has been associated with later development of asthma, wheezing, abnormal pulmonary function, and sensitization. Our aim was to determine the differential effect within monozygotic (MZ) twin pairs discordant for severe RSV bronchiolitis in infancy on...

  6. Transmission of human respiratory syncytial virus in the immunocompromised ferret model

    NARCIS (Netherlands)

    de Waal, L. (Leon); S.L. Smits (Saskia); E.J.B. Veldhuis Kroeze (Edwin); G. van Amerongen (Geert); Pohl, M.O. (Marie O.); Osterhaus, A.D.M.E. (Albert D. M. E.); K.J. Stittelaar (Koert)

    2018-01-01

    textabstractHuman respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with

  7. Variation of respiratory syncytial virus and the relation with meteorological factors in different winter seasons.

    NARCIS (Netherlands)

    Meerhoff, T.J.; Paget, W.J.; Kimpen, J.L.; Schellevis, F.

    2009-01-01

    Background: Respiratory syncytial virus (RSV) is the most important viral agent causing severe respiratory disease in infants and children. In temperate climates, RSV activity typically peaks during winter. We have described the seasonal variation in RSV activity and investigated which

  8. Bovine respiratory syncytial virus: first serological evidence in Uruguay.

    Science.gov (United States)

    Costa, M; García, L; Yunus, A S; Rockemann, D D; Samal, S K; Cristina, J

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in calves resulting in a substantial economic loss for the cattle industry worldwide. In order to determine the presence of BRSV in Uruguay, an immunoenzymatic test was set up, using a recombinant BRSV nucleocapsid (N) protein as the antigen. The N protein was produced in Sf9 insect cells by a recombinant baculovirus expressing the N protein. Serum samples collected from one hundred cattle from four different geographic regions of Uruguay were analyzed. Antibodies against the N protein of BRSV were detected in 95% of the serum samples analyzed. These results show for the first time the presence of BRSV antibodies and suggest a widespread BRSV infection in the cattle population of Uruguay.

  9. Caesarean Section and Hospitalization for Respiratory Syncytial Virus Infection

    DEFF Research Database (Denmark)

    Kristensen, Kim; Fisker, Niels; Haerskjold, Ann

    2015-01-01

    BACKGROUND AND OBJECTIVE:: Hospitalization for respiratory syncytial virus (RSV) infection and asthma share common determinants, and meta-analyses indicate that children delivered by caesarean section (CS) are at increased risk of asthma. We aimed to investigate whether birth by CS is associated...... regression with adjustment for prematurity, asphyxia, birth weight, multiple births, single parenthood, maternal smoking during pregnancy, older siblings, and asthma diagnoses up to 2 weeks before hospitalization for RSV infection, to compare the effects of acute or elective CS versus vaginal delivery...... infection in children born by acute CS and by elective CS were 1.09 (1.01 - 1.17) and 1.27 (1.19 - 1.36), respectively. The effect of elective CS remained unchanged throughout the first two years of life (p = 0.53), whereas the effect of acute CS was only present in the second year of life (p = 0...

  10. Overview of respiratory syncytial virus disease in young children

    Directory of Open Access Journals (Sweden)

    Hoopes JM

    2012-07-01

    Full Text Available J Michael Hoopes1, Veena R Kumar21Medical Information, 2Medical and Scientific Affairs, MedImmune, LLC, Gaithersburg, MD, USAAbstract: Respiratory tract illnesses associated with respiratory syncytial virus (RSV were first reported more than 160 years ago and gained acceptance as a major respiratory pathogen in the late 1950s. Annual epidemics show a seasonal pattern typically beginning in the late fall and ending in early spring, averaging 5 months in length, and varying in time of onset, offset, and duration depending on geographic location. Manifestations of RSV illness primarily involve the upper respiratory tract but can spread to the lower airways and lead to bronchiolitis and/or pneumonia. Initial infection occurs in approximately two-thirds of children during the first year of life; nearly all children are infected at least once by 2 years of age. Reinfection is common throughout life, but initial illness during infancy generally presents with the most severe symptoms. Medical risk conditions that consistently predispose young children to serious lower respiratory tract infection (LRTI include congenital heart disease, chronic lung disease, and premature birth. Serious LRTI due to RSV is the leading cause of hospitalization in infants and young children worldwide and annual mean hospital expenses have been estimated to exceed 1 billion dollars in the United States. Young children incur more inpatient and outpatient visits for RSV LRTI than for influenza. RSV has a greater impact than influenza on hospitalization in infants with respect to length of stay, severity/course of disease, and resultant needs for ancillary treatments. Unlike many other childhood illnesses, a vaccine is not currently available for preventing RSV disease.Keywords: bronchopulmonary dysplasia, infants, hospitalization, prematurity, respiratory syncytial virus

  11. Increased detection of respiratory syncytial virus, influenza viruses, parainfluenza viruses, and adenoviruses with real-time PCR in samples from patients with respiratory symptoms

    NARCIS (Netherlands)

    van de Pol, Alma C.; van Loon, Anton M.; Wolfs, Tom F. W.; Jansen, Nicolaas J. G.; Nijhuis, Monique; Breteler, Els Klein; Schuurman, Rob; Rossen, John W. A.

    Respiratory samples (n = 267) from hospitalized patients with respiratory symptoms were tested by real-time PCR, viral culture, and direct immunofluorescence for respiratory syncytial virus, influenza virus, parainfluenza viruses, and adenoviruses. Compared with conventional diagnostic tests,

  12. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders

    OpenAIRE

    Lehners, Nicola; Tabatabai, Julia; Prifert, Christiane; Wedde, Marianne; Puthenparambil, Joe; Weissbrich, Benedikt; Biere, Barbara; Schweiger, Brunhilde; Egerer, Gerlinde; Schnitzler, Paul

    2016-01-01

    Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV o...

  13. Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus.

    Science.gov (United States)

    Rincheval, Vincent; Lelek, Mickael; Gault, Elyanne; Bouillier, Camille; Sitterlin, Delphine; Blouquit-Laye, Sabine; Galloux, Marie; Zimmer, Christophe; Eleouet, Jean-François; Rameix-Welti, Marie-Anne

    2017-09-15

    Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term "IB-associated granules" (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.

  14. The biennial cycle of respiratory syncytial virus outbreaks in Croatia

    Directory of Open Access Journals (Sweden)

    Drazenovic Vladimir

    2008-01-01

    Full Text Available Abstract The paper analyses the epidemic pattern of respiratory syncytial virus (RSV outbreaks in children in Croatia. Over a period of 11 consecutive winter seasons (1994–2005 3,435 inpatients from Zagreb County aged from infancy to 10 years who were hospitalised with acute respiratory tract infections were tested for RSV-infection. RSV was identified in nasopharyngeal secretions of patients by virus isolation in cell culture and by detection of viral antigen with monoclonal antibodies. In the Zagreb area, RSV outbreaks were proven to vary in a two-year cycle, which was repeated every 23–25 months. This biennial cycle comprised one larger and one smaller season. Climate factors correlated significantly with the number of RSV cases identified only in the large seasons, which suggests that the biennial cycle is likely to continue regardless of meteorological conditions. Knowledge of this biennial pattern should be useful in predicting the onset of RSV outbreaks in Croatia, and would facilitate planning for the prevention and control of RSV infections in the region.

  15. Nosocomial infections by respiratory syncytial virus in children

    Directory of Open Access Journals (Sweden)

    Maren Karina Machado Echeverría

    2017-01-01

    Full Text Available Introduction: Acute lower respiratory infections cause high morbidity and mortality in children. Respiratory syncytial virus (RSV is the most prevalent agent. Some viruses cause serious nosocomial infections. In Uruguay, there is no knowledge about the morbidity and mortality of nosocomial infections by RSV. Objective: To determine the prevalence and characteristics of RSV nosocomial infections. Methodology: A descriptive study of acute lower respiratory infections caused by RSV in patients younger than two years, between 1/1/2005 and 31/12/2008 at the Hospital Pediátrico del Centro Hospitalario Pereira Rossell, was made. Results: Were identified 59 patients who represented an annual rate lower than 2/1000 discharges. The monthly distribution of cases was similar to the respiratory infections. No outbreaks were reported. The age of the patients had an average of 8.9 months, 39 were younger than one year, 23 had one or more risk factors for severe disease. Six patients required admission to intensive care unit, all required invasive ventilation, 3 died, none had chronic respiratory failure following the RSV nosocomial infection. Conclusions: During the study period, the RSV nosocomial infections showed a low prevalence, despite it highly contagiousness. They mainly affected young children, carriers of risk factors for severe ALRI. Their evolution was similar to that reported for RSV respiratory infections community acquired. It is important to maintain standards for the control of nosocomial infections, to prevent nosocomial transmission of RSV and prevent the onset of severe disease in hospitalized patients.

  16. Burden of Severe Respiratory Syncytial Virus Disease Among 33-35 Weeks' Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons.

    LENUS (Irish Health Repository)

    Anderson, Evan J

    2017-02-01

    Moderate-late preterm infants, 33-35 weeks\\' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants.

  17. Respiratory syncytial virus (RSV) pneumonia in a southern muriqui (Brachyteles arachnoides).

    Science.gov (United States)

    Santos, S V; Strefezzi, R F; Pissinatti, A; Takakura, C F H; Kanamura, C; Duarte, M I S; Catão-Dias, J L

    2012-12-01

    An adult male Brachyteles arachanoides, kept in captivity since 1990, was found dead without apparent clinical evidence. Necropsy report, histopathology, immunohistochemistry, and ultrastructural examination were conducted. Pulmonary syncytial cells were positive for respiratory syncytial virus (RSV), and ultrastructural examination revealed viral particles inside macrophages compatible with the Paramyxoviridae family. Muriquis are susceptible to RSV pneumonia followed by respiratory distress syndrome and death. © 2012 John Wiley & Sons A/S.

  18. Challenges and opportunities in developing respiratory syncytial virus therapeutics.

    Science.gov (United States)

    Simões, Eric A F; DeVincenzo, John P; Boeckh, Michael; Bont, Louis; Crowe, James E; Griffiths, Paul; Hayden, Frederick G; Hodinka, Richard L; Smyth, Rosalind L; Spencer, Keith; Thirstrup, Steffen; Walsh, Edward E; Whitley, Richard J

    2015-03-15

    Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial virus (RSV) infections. The practicalities of clinical trials and establishing reliable outcome measures in different target groups were discussed in the context of the regulatory pathways that could accelerate the translation of promising compounds into licensed agents. RSV drug development is hampered by the perceptions of a relatively small and fragmented market that may discourage major pharmaceutical company investment. Conversely, the public health need is far too large for RSV to be designated an orphan or neglected disease. Recent advances in understanding RSV epidemiology, improved point-of-care diagnostics, and identification of candidate antiviral drugs argue that the major obstacles to drug development can and will be overcome. Further progress will depend on studies of disease pathogenesis and knowledge provided from controlled clinical trials of these new therapeutic agents. The use of combinations of inhibitors that have different mechanisms of action may be necessary to increase antiviral potency and reduce the risk of resistance emergence. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  19. Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis

    International Nuclear Information System (INIS)

    Hirayama, K.; Sakazaki, Hiromi; Murakami, Seiko; Yonezawa, Sumiko; Fujimoto, Keiji; Seto, Toshiyuki; Tanaka, Katsuji; Hattori, Hideji; Matsuoka, Osamu; Murata, Ryosuke

    1999-01-01

    We report on a 3-year-old girl with respiratory syncytial virus (RSV) encephalitis manifested by disturbance of consciousness, conjugate eye deviation, anuria, truncal ataxia and intention tremor. T2-weighted magnetic resonance imaging (MRI) showed hyperintense areas in the cerebellar cortex. No lesion was detected in the cerebral cortex, pons or spinal cord. The hyperintense areas in the cerebellar cortex diminished with recovery from the clinical manifestations and had resolved 2 months after onset. The MRI lesions in the cerebellum were considered to be due to oedema. SPECT and positron emission tomography (PET), performed 3 months after onset, disclosed areas of hypoperfusion and hypometabolism at the same sites. One year after onset, MRI showed mild atrophy of the cerebellum. Hypoperfusion on SPECT and hypometabolism on PET remained. Neuroimaging showed that ataxia and tremor in this case were the result of cerebellitis. The patient has no neurological deficit except for mild truncal ataxia. This patient is a rare example of RSV encephalitis. (orig.)

  20. Respiratory Syncytial Virus Entry Inhibitors Targeting the F Protein

    Directory of Open Access Journals (Sweden)

    Shibo Jiang

    2013-01-01

    Full Text Available Human respiratory syncytial virus (RSV is the main viral cause of respiratory tract infection in infants as well as some elderly and high-risk adults with chronic pulmonary disease and the severely immunocompromised. So far, no specific anti-RSV therapeutics or effective anti-RSV vaccines have been reported. Only one humanized monoclonal antibody, Palivizumab, has been approved for use in high-risk infants to prevent RSV infection. Ribavirin is the only drug licensed for therapy of RSV infection, but its clinical use is limited by its nonspecific anti-RSV activity, toxic effect, and relatively high cost. Therefore, development of novel effective anti-RSV therapeutics is urgently needed. The RSV envelope glycoprotein F plays an important role in RSV fusion with, and entry into, the host cell and, consequently, serves as an attractive target for developing RSV entry inhibitors. This article reviews advances made in studies of the structure and function of the F protein and the development of RSV entry inhibitors targeting it.

  1. Respiratory syncytial virus tracking using internet search engine data.

    Science.gov (United States)

    Oren, Eyal; Frere, Justin; Yom-Tov, Eran; Yom-Tov, Elad

    2018-04-03

    Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in children less than 1 year of age in the United States. Internet search engine queries may provide high resolution temporal and spatial data to estimate and predict disease activity. After filtering an initial list of 613 symptoms using high-resolution Bing search logs, we used Google Trends data between 2004 and 2016 for a smaller list of 50 terms to build predictive models of RSV incidence for five states where long-term surveillance data was available. We then used domain adaptation to model RSV incidence for the 45 remaining US states. Surveillance data sources (hospitalization and laboratory reports) were highly correlated, as were laboratory reports with search engine data. The four terms which were most often statistically significantly correlated as time series with the surveillance data in the five state models were RSV, flu, pneumonia, and bronchiolitis. Using our models, we tracked the spread of RSV by observing the time of peak use of the search term in different states. In general, the RSV peak moved from south-east (Florida) to the north-west US. Our study represents the first time that RSV has been tracked using Internet data results and highlights successful use of search filters and domain adaptation techniques, using data at multiple resolutions. Our approach may assist in identifying spread of both local and more widespread RSV transmission and may be applicable to other seasonal conditions where comprehensive epidemiological data is difficult to collect or obtain.

  2. Treatment of respiratory syncytial virus infections in children.

    Science.gov (United States)

    Mäkelä, M J; Ruuskanen, O; Ogra, P L

    1994-10-01

    Treatment of the infections caused by the respiratory syncytial virus (RSV) has varied largely in different centres. Recently, however, management practices have become more clear based on a number of studies. An infant with RSV bronchiolitis should be hospitalized in case of insufficient oxygenation, as measured by pulse oximetry, and additional oxygen should be supplied. Mist treatment and physiotherapy are not beneficial. Bronchodilators seem to be the drug of choice in most infants with bronchiolitis. Use of corticosteroids has not been supported by data received from most studies although they are generally used. Ribavirin should be used only with high-risk patients such as immunosuppressed children. Despite the common prescription of antibiotics, they should only be given to patients with verified bacterial infection. In the future, immunotherapy including aerosolized IgG may be an alternative in treatment of RSV infections. Until an efficient vaccine is brought to clinical use, the best way to limit nosocomial spread of infections is to use cohort nursing and gowns.

  3. PROPHYLACTIC ADMINISTRATION OF RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN TO HIGH-RISK INFANTS AND YOUNG-CHILDREN

    NARCIS (Netherlands)

    GROOTHUIS, [No Value; SIMOES, EAF; LEVIN, MJ; HALL, CB; LONG, CE; RODRIGUEZ, WJ; ARROBIO, J; MEISSNER, HC; FULTON, DR; WELLIVER, RC; TRISTRAM, DA; SIBER, GR; PRINCE, GA; VANRADEN, M; HEMMING, VG

    1993-01-01

    Background. Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common

  4. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J. B. M.; Bos, A. P.; Lutter, R.; Rossen, J. W. A.; Schuurman, R.

    2006-01-01

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  5. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J B M; Bos, A P; Lutter, R; Rossen, J W A; Schuurman, R

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  6. Equal virulence of rhinovirus and respiratory syncytial virus in infants hospitalized for lower respiratory tract infection

    NARCIS (Netherlands)

    van Leeuwen, J.C.; Goossens, L.K.; Hendrix, R.; van der Palen, Jacobus Adrianus Maria; Lusthusz, A.; Thio, B.J.

    2012-01-01

    Respiratory syncytial virus (RSV) and rhinovirus (RV) are predominant viruses associated with lower respiratory tract infection in infants. We compared the symptoms of lower respiratory tract infection caused by RSV and RV in hospitalized infants. RV showed the same symptoms as RSV, so on clinical

  7. Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus

    NARCIS (Netherlands)

    Habibi, Maximillian S; Jozwik, Agnieszka; Makris, Spyridon; Dunning, Jake; Paras, Allan; DeVincenzo, John P; de Haan, Cornelis A M; Wrammert, Jens; Openshaw, Peter J M; Chiu, Christopher

    2015-01-01

    RATIONALE: Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of

  8. Genetic and antigenic analysis of the G attachment protein of bovine respiratory syncytial virus strains

    DEFF Research Database (Denmark)

    Elvander, M.; Vilcek, S.; Baule, C.

    1998-01-01

    Antigenic and genetic studies of bovine respiratory syncytial virus (BRSV) were made on isolates obtained from three continents over 27 years. Antigenic variation between eight isolates was initially determined using protein G-specific monoclonal antibodies. Four distinct reaction patterns were...... of a 731 nucleotide fragment in the G protein gene. Nine of the BRSV strains were analysed by direct sequencing of RT-PCR amplicons whereas sequences of 18 BRSV and three human respiratory syncytial virus (HRSV) strains were obtained from GenBank. The analysis revealed similarities of 88-100% among BRSV...

  9. Respiratory Syncytial Virus Hospitalizations in Healthy Preterm Infants

    Science.gov (United States)

    Margulis, Andrea V.; Samuel, Miny; Lohr, Kathleen N.

    2016-01-01

    Background: Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29–35 weeks of gestational age not given RSV immunoprophylaxis. We performed a systematic review and qualitative synthesis of these studies. Methods: Two experienced reviewers used prespecified inclusion/exclusion criteria to screen titles/abstracts and full-text studies using MEDLINE, Embase, BIOSIS and Cochrane Library (January 1, 1985, to November 6, 2014). We abstracted data on risk factors for RSV hospitalization, incidence and short- and long-term outcomes of RSV hospitalization. Using standard procedures, we assessed study risk of bias and graded strength of evidence (SOE). Results: We identified 4754 records and reviewed 27. Important risk factors for RSV hospitalization included young age during the RSV season, having school-age siblings and day-care attendance, with odds ratios >2.5 in at least one study (high SOE). Incidence rates for RSV hospitalizations ranged from 2.3% to 10% (low SOE). Length of hospital stays ranged from 3.8 to 6.1 days (low SOE). Recurrent wheezing rates ranged from 20.7% to 42.8% 1 to 2 years after RSV hospitalization (low SOE). Conclusions: Young chronological age and some environmental risk factors are important clinical indicators of an increased risk of RSV hospitalization in healthy preterm infants 32 to 35 weeks of gestational age. SOE was low for estimates of incidence of RSV hospitalizations, in-hospital resource use and recurrent wheezing in this population. Studies were inconsistent in study characteristics, including weeks of gestational age, age during RSV season and control for confounding factors. PMID:27093166

  10. Motavizumab, A Neutralizing Anti-Respiratory Syncytial Virus (Rsv Monoclonal Antibody Significantly Modifies The Local And Systemic Cytokine Responses Induced By Rsv In The Mouse Model

    Directory of Open Access Journals (Sweden)

    Jafri Hasan S

    2007-10-01

    Full Text Available Abstract Motavizumab (MEDI-524 is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL and serum samples were obtained at days 1, 5 (acute and 28 (long-term post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY for simultaneous quantitation of 18 cytokines: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-α, MCP-1, RANTES, IFN-γ and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p

  11. Modification of the respiratory syncytial virus f protein in virus-like particles impacts generation of B cell memory.

    Science.gov (United States)

    Schmidt, Madelyn R; McGinnes-Cullen, Lori W; Kenward, Sarah A; Willems, Kristin N; Woodland, Robert T; Morrison, Trudy G

    2014-09-01

    Immunization with virus-like particles (VLPs) containing the Newcastle disease virus (NDV) core proteins, NP and M, and two chimera proteins (F/F and H/G) containing the respiratory syncytial virus (RSV) F- and G-protein ectodomains fused to the transmembrane and cytoplasmic domains of NDV F and HN proteins, respectively, stimulated durable RSV-neutralizing antibodies, F-protein-specific long-lived, bone marrow-associated plasma cells (LLPCs), and B cell memory, in striking contrast to RSV infection, which did not (M. R. Schmidt, L. W. McGinnes, S. A. Kenward, K. N. Willems, R. T. Woodland, and T. G. Morrison, J. Virol. 86:11654-11662, 2012). Here we report the characterization of a VLP with an RSV F-protein ectodomain fused to the NDV F-protein heptad repeat 2 (HR2), transmembrane, and cytoplasmic domain sequences, creating a chimera with two tandem HR2 domains, one from the RSV F protein and the other from the NDV F-protein ectodomain (F/HR2F). The F/HR2F chimera protein was efficiently assembled into VLPs along with the H/G chimera protein. This VLP (VLP-H/G+F/HR2F) stimulated anti-F-protein and anti-G-protein IgG, durable RSV-neutralizing antibodies, and anti-RSV F-protein-secreting LLPCs. However, the subtypes of anti-F-protein IgG induced were different from those elicited by VLPs containing the F/F chimera (VLP-H/G+F/F). Most importantly, VLP-H/G+F/HR2F did not induce RSV F-protein-specific B cell memory, as shown by the adoptive transfer of B cells from immunized animals to immunodeficient animals. The VLP did, however, induce B cell memory specific to the RSV G protein. Thus, the form of the F protein has a direct role in inducing anti-F-protein B cell memory. The development of vaccines for respiratory syncytial virus (RSV) is hampered by a lack of a clear understanding of the requirements for eliciting protective as well as durable human immune responses to virus antigens. The results of this study indicate that the form of the RSV F protein has a direct

  12. Risk factors for admission and the role of respiratory syncytial virus ...

    African Journals Online (AJOL)

    Background. Risk factors for admission of children with acute bronchiolitis have remained controversial. Technological advances in the measurements of cytotoxic T-lymphocyte. (CTL) activity, enable respiratory syncytial virus (RSV)- specific CTL activity to be studied in infants with bronchiolitis for the first time. We evaluated ...

  13. Respiratory syncytial virus-specific CD8(+) memory T cell responses in elderly persons

    NARCIS (Netherlands)

    de Bree, GJ; Heidema, J; van Leeuwen, EMM; van Bleek, GM; Jonkers, RE; Jansen, HM; van Lier, RAW; Out, TA

    2005-01-01

    Background. We investigated respiratory syncytial virus (RSV)-specific CD8(+) memory T cell responses in healthy control participants (n = 31) and in patients with chronic obstructive pulmonary disease (COPD) n = 9), with respect to frequency, memory phenotype, and proliferative requirements.

  14. Molecular epidemiology of respiratory syncytial virus during the 2009-2010 season in Latvia.

    Science.gov (United States)

    Balmaks, Reinis; Ribakova, Irina; Gardovska, Dace; Kazaks, Andris

    2013-05-01

    For the first time, we studied molecular epidemiology of respiratory syncytial virus in hospitalized children in Latvia. During the study period, ten unique group A and three group B strains were identified and assigned to a single genotype within each group-GA2 for group A and BA-IV for group B.

  15. Global respiratory syncytial virus-associated mortality in young children (RSV GOLD) : a retrospective case series

    NARCIS (Netherlands)

    Scheltema, Nienke M.; Gentile, Angela; Lucion, Florencia; Nokes, D. James; Munywoki, Patrick K.; Madhi, Shabir A.; Groome, Michelle J; Cohen, Cheryl; Moyes, Jocelyn; Thorburn, Kentigern; Thamthitiwat, Somsak; Oshitani, Hitoshi; Lupisan, Socorro P.; Gordon, Aubree; Sánchez, José F.; O'Brien, Katherine L.; Gessner, Bradford D.; Sutanto, Agustinus; Mejias, Asuncion; Ramilo, Octavio; Khuri-Bulos, Najwa; Halasa, Natasha; de-Paris, Fernanda; Pires, Márcia Rosane; Spaeder, Michael C.; Paes, Bosco A.; Simões, Eric A F; Leung, Ting F.; da Costa Oliveira, Maria Tereza; de Freitas Lázaro Emediato, Carla Cecília; Bassat, Quique; Butt, Warwick; Chi, Hsin; Aamir, Uzma Bashir; Ali, Asad; Lucero, Marilla G.; Fasce, Rodrigo A.; Lopez, Olga; Rath, Barbara A.; Polack, Fernando P.; Papenburg, Jesse; Roglić, Srđan; Ito, Hisato; Goka, Edward A.; Grobbee, Diederick E.; Nair, Harish; Bont, Louis J.

    2017-01-01

    Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related

  16. Incidence and seasonality of respiratory syncytial virus hospitalisations in young children in Denmark, 2010 to 2015

    DEFF Research Database (Denmark)

    Jepsen, Martin T; Trebbien, Ramona; Emborg, Hanne Dorthe

    2018-01-01

    For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual...... RSV-associated admissions in children ... be maternal vaccination due to general challenges in achieving sufficient and protective immune responses in young infants....

  17. Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization

    DEFF Research Database (Denmark)

    Kristensen, Kim; Hjuler, Thomas; Ravn, Henrik

    2012-01-01

    Little is known about how chronic conditions other than prematurity, heart disease, and Down syndrome affect the risk and severity of hospitalization for respiratory syncytial virus (RSV). We assess the risk and severity of RSV hospitalization in children with chronic conditions in this register-...

  18. Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing

    NARCIS (Netherlands)

    Bont, L.; van Aalderen, W. M.; Versteegh, J.; Brus, F.; Draaisma, J. T.; Pekelharing-Berghuis, M.; van Diemen-Steenvoorde, R. A.; Kimpen, J. L.

    2001-01-01

    Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. To determine clinical predictors for airway

  19. Lower respiratory tract infection caused by respiratory syncytial virus : current management and new therapeutics

    NARCIS (Netherlands)

    Mazur, Natalie; Martinon-Torres, Federico; Baraldi, Eugenio; Fauroux, Brigitte; Greenough, Anne; Heikkinen, Terho; Manzoni, Paolo; Mejias, Asuncion; Nair, Harish; Papadopoulos, Nikolaos G.; Polack, Fernando P.; Ramilo, Octavio; Sharland, Mike; Stein, Renato; Madhi, Shabir A.; Bont, Louis

    2015-01-01

    Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and

  20. Cost-effectiveness of respiratory syncytial virus (RSV) vaccination of dutch elderly

    NARCIS (Netherlands)

    Pouwels, K.; Meijboom, M.; Luytjes, W.; Hak, E.; Postma, M.

    2011-01-01

    OBJECTIVES: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of morbidity, mortality and health-care resource use in the elderly. Therefore we determined whether there are specific levels of vaccine cost and effectiveness for which a hypothetical RSV-vaccine for

  1. Pericarditis mediated by respiratory syncytial virus in a hematopoietic stem cell transplant patient.

    Science.gov (United States)

    Rubach, M P; Pavlisko, E N; Perfect, J R

    2013-08-01

    We describe a case of pericarditis and large pericardial effusion in a 63-year-old African-American man undergoing autologous hematopoietic stem cell transplant for multiple myeloma. Pericardial tissue biopsy demonstrated fibrinous pericarditis, and immunohistochemistry stains were positive for respiratory syncytial virus. The patient improved with oral ribavirin and intravenous immune globulin infusions. © 2013 John Wiley & Sons A/S.

  2. Impact of wheezing after respiratory syncytial virus infection on health-related quality of life

    NARCIS (Netherlands)

    Bont, Louis; Steijn, Marijke; van Aalderen, Wim M. C.; Kimpen, Jan L. L.

    2004-01-01

    Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is often followed by recurrent wheezing episodes during childhood. The effect of postbronchiolitis wheezing on the well-being of the child is not known. This study aimed to determine the impact of RSV LRTI

  3. Challenges and Opportunities in Developing Respiratory Syncytial Virus Therapeutics

    NARCIS (Netherlands)

    Simoes, Eric A. F.; DeVincenzo, John P.; Boeckh, Michael; Bont, LJ; Crowe, James E.; Griffiths, Paul; Hayden, Frederick G.; Hodinka, Richard L.; Smyth, Rosalind L.; Spencer, Keith; Thirstrup, Steffen; Walsh, Edward E.; Whitley, Richard J.

    2015-01-01

    Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial

  4. Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity.

    Science.gov (United States)

    Hendricks, Matthew R; Lashua, Lauren P; Fischer, Douglas K; Flitter, Becca A; Eichinger, Katherine M; Durbin, Joan E; Sarkar, Saumendra N; Coyne, Carolyn B; Empey, Kerry M; Bomberger, Jennifer M

    2016-02-09

    Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients' acquisition of chronic P. aeruginosa infections and respiratory virus infection, little is known about the mechanism by which chronic P. aeruginosa infections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondary P. aeruginosa biofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotes P. aeruginosa biofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.

  5. Serological responses in calves to vaccines against bovine respiratory syncytial, infectious bovine rhinotracheitis, bovine viral diarrhoea and parainfluenza-3 viruses.

    Science.gov (United States)

    Tollis, M; Di Trani, L; Cordioli, P; Vignolo, E; Di Pasquale, I

    1996-01-01

    The Istituto Superiore di Sanità (ISS), the National Veterinary Services Laboratory in Italy, is in charge of assessing the quality, safety and efficacy of veterinary vaccines before and after licensing. To evaluate the relative potency of several vaccines against bovine respiratory syncytial virus (BRSV), infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhoea virus (BVDV) and parainfluenza-3 virus (PI3V), the serological responses in vaccinated calves were studied. Vaccination with any of the vaccines under study induced specific antibody titres against the different viral antigens. The differences of the mean antibody titres within and among the test group vaccines were statistically significant. The results confirm and support those obtained by other authors in similar studies, suggesting that serological responses in vaccinated calves can be used as a helpful means of assessing the relative potency of vaccines against viral respiratory diseases of cattle. The criteria allowing such an evaluation are discussed.

  6. Respiratory Syncytial Virus Fusion Protein-Induced Toll-Like Receptor 4 (TLR4) Signaling Is Inhibited by the TLR4 Antagonists Rhodobacter sphaeroides Lipopolysaccharide and Eritoran (E5564) and Requires Direct Interaction with MD-2

    Science.gov (United States)

    Rallabhandi, Prasad; Phillips, Rachel L.; Boukhvalova, Marina S.; Pletneva, Lioubov M.; Shirey, Kari Ann; Gioannini, Theresa L.; Weiss, Jerrold P.; Chow, Jesse C.; Hawkins, Lynn D.; Vogel, Stefanie N.; Blanco, Jorge C. G.

    2012-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Toll-like receptor 4 (TLR4), a signaling receptor for structurally diverse microbe-associated molecular patterns, is activated by the RSV fusion (F) protein and by bacterial lipopolysaccharide (LPS) in a CD14-dependent manner. TLR4 signaling by LPS also requires the presence of an additional protein, MD-2. Thus, it is possible that F protein-mediated TLR4 activation relies on MD-2 as well, although this hypothesis has not been formally tested. LPS-free RSV F protein was found to activate NF-κB in HEK293T transfectants that express wild-type (WT) TLR4 and CD14, but only when MD-2 was coexpressed. These findings were confirmed by measuring F-protein-induced interleukin 1β (IL-1β) mRNA in WT versus MD-2−/− macrophages, where MD-2−/− macrophages failed to show IL-1β expression upon F-protein treatment, in contrast to the WT. Both Rhodobacter sphaeroides LPS and synthetic E5564 (eritoran), LPS antagonists that inhibit TLR4 signaling by binding a hydrophobic pocket in MD-2, significantly reduced RSV F-protein-mediated TLR4 activity in HEK293T-TLR4–CD14–MD-2 transfectants in a dose-dependent manner, while TLR4-independent NF-κB activation by tumor necrosis factor alpha (TNF-α) was unaffected. In vitro coimmunoprecipitation studies confirmed a physical interaction between native RSV F protein and MD-2. Further, we demonstrated that the N-terminal domain of the F1 segment of RSV F protein interacts with MD-2. These data provide new insights into the importance of MD-2 in RSV F-protein-mediated TLR4 activation. Thus, targeting the interaction between MD-2 and RSV F protein may potentially lead to novel therapeutic approaches to help control RSV-induced inflammation and pathology. PMID:22872782

  7. Phase-I study MEDI-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children.

    Science.gov (United States)

    Gomez, Margarita; Mufson, Maurice A; Dubovsky, Filip; Knightly, Conor; Zeng, Wen; Losonsky, Genevieve

    2009-07-01

    A live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine was evaluated in healthy respiratory syncytial virus/parainfluenza virus type 3 seropositive children aged 1 to 9 years. Three cohorts of 40 children were randomized 1:1 to receive 10, 10, or 10 median tissue culture infectious dose50 MEDI-534 vaccine or placebo. The vaccine's safety profile was similar to placebo, no viral shedding was detected, and the vaccine was minimally immunogenic.

  8. Intranasal administration of antibody-bound respiratory syncytial virus particles efficiently primes virus-specific immune responses in mice

    NARCIS (Netherlands)

    Kruijsen, Debby; Einarsdottir, Helga K.; Schijf, Marcel A.; Coenjaerts, Frank E.; van der Schoot, Ellen C.; Vidarsson, Gestur; van Bleek, Grada M.

    2013-01-01

    Infants are protected from a severe respiratory syncytial virus (RSV) infection in the first months of life by maternal antibodies or by prophylactically administered neutralizing antibodies. Efforts are under way to produce RSV-specific antibodies with increased neutralizing capacity compared to

  9. Respiratory Syncytial Virus (RSV RNA loads in peripheral blood correlates with disease severity in mice

    Directory of Open Access Journals (Sweden)

    Torres Juan

    2010-09-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. Methods Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. Results RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. Conclusions RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.

  10. Cimicifuga foetida L. inhibited human respiratory syncytial virus in HEp-2 and A549 cell lines.

    Science.gov (United States)

    Wang, Kuo Chih; Chang, Jung San; Chiang, Lien Chai; Lin, Chun Ching

    2012-01-01

    Human respiratory syncytial virus (HRSV) causes serious pediatric infection of the lower respiratory tract without effective therapeutic modality. Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) has been proven to be effective at inhibiting HRSV-induced plaque formation, and Cimicifuga foetida is the major constituent of SMGGT. We tested the hypothesis that C. foetida effectively inhibited the cytopathic effects of HRSV by a plaque reduction assay in both human upper (HEp2) and lower (A549) respiratory tract cell lines. Its ability to stimulate anti-viral cytokines was evaluated by an enzyme-linked immunosorbent assay (ELISA). C. foetida dose-dependently inhibited HRSV-induced plaque formation (p < 0.0001) before and after viral inoculation, especially in A549 cells (p < 0.0001). C. foetida dose-dependently inhibited viral attachment (p < 0.0001) and could increase heparins effect on viral attachment. In addition, C. foetida time-dependently and dose-dependently (p < 0.0001) inhibited HRSV internalization. C. foetida could stimulate epithelial cells to secrete IFN-β to counteract viral infection. However, C. foetida did not stimulate TNF-α secretion. Therefore, C. foetida could be useful in managing HRSV infection. This is the first evidence to support that C. foetida possesses antiviral activity.

  11. Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

    OpenAIRE

    Scheltema, Nienke M; Gentile, Angela; Lucion, Florencia; Nokes, D James; Munywoki, Patrick K; Madhi, Shabir A; Groome, Michelle J; Cohen, Cheryl; Moyes, Jocelyn; Thorburn, Kentigern; Thamthitiwat, Somsak; Oshitani, Hitoshi; Lupisan, Socorro P; Gordon, Aubree; S?nchez, Jos? F

    2017-01-01

    Summary Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic charac...

  12. Neonatal Calf Infection with Respiratory Syncytial Virus: Drawing Parallels to the Disease in Human Infants

    OpenAIRE

    Sacco, Randy E.; McGill, Jodi L.; Palmer, Mitchell V.; Lippolis, John D.; Reinhardt, Timothy A.; Nonnecke, Brian J.

    2012-01-01

    Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of ...

  13. Protective efficacy and immunogenicity of a combinatory DNA vaccine against Influenza A Virus and the Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Viktoria Stab

    Full Text Available The Respiratory Syncytial Virus (RSV and Influenza A Virus (IAV are both two major causative agents of severe respiratory tract infections in humans leading to hospitalization and thousands of deaths each year. In this study, we evaluated the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the single component vaccines against both diseases in a mouse model. Intramuscular electroporation with plasmids expressing the hemagglutinin (HA of IAV and the F protein of RSV induced strong humoral immune responses regardless if they were delivered in combination or alone. In consequence, high neutralizing antibody titers were detected, which conferred protection against a lethal challenge with IAV. Furthermore, the viral load in the lungs after a RSV infection could be dramatically reduced in vaccinated mice. Concurrently, substantial amounts of antigen-specific, polyfunctional CD8⁺ T-cells were measured after vaccination. Interestingly, the cellular response to the hemagglutinin was significantly reduced in the presence of the RSV-F encoding plasmid, but not vice versa. Although these results indicate a suppressive effect of the RSV-F protein, the protective efficacy of the combinatory vaccine was comparable to the efficacy of both single-component vaccines. In conclusion, the novel combinatory vaccine against RSV and IAV may have great potential to reduce the rate of severe respiratory tract infections in humans without increasing the number of necessary vaccinations.

  14. Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils.

    Directory of Open Access Journals (Sweden)

    Giselle A Funchal

    Full Text Available Acute viral bronchiolitis by Respiratory Syncytial Virus (RSV is the most common respiratory illness in children in the first year of life. RSV bronchiolitis generates large numbers of hospitalizations and an important burden to health systems. Neutrophils and their products are present in the airways of RSV-infected patients who developed increased lung disease. Neutrophil Extracellular Traps (NETs are formed by the release of granular and nuclear contents of neutrophils in the extracellular space in response to different stimuli and recent studies have proposed a role for NETs in viral infections. In this study, we show that RSV particles and RSV Fusion protein were both capable of inducing NET formation by human neutrophils. Moreover, we analyzed the mechanisms involved in RSV Fusion protein-induced NET formation. RSV F protein was able to induce NET release in a concentration-dependent fashion with both neutrophil elastase and myeloperoxidase expressed on DNA fibers and F protein-induced NETs was dismantled by DNase treatment, confirming that their backbone is chromatin. This viral protein caused the release of extracellular DNA dependent on TLR-4 activation, NADPH Oxidase-derived ROS production and ERK and p38 MAPK phosphorylation. Together, these results demonstrate a coordinated signaling pathway activated by F protein that led to NET production. The massive production of NETs in RSV infection could aggravate the inflammatory symptoms of the infection in young children and babies. We propose that targeting the binding of TLR-4 by F protein could potentially lead to novel therapeutic approaches to help control RSV-induced inflammatory consequences and pathology of viral bronchiolitis.

  15. Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2018-03-01

    Full Text Available Respiratory syncytial virus (RSV and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell

  16. Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus.

    Science.gov (United States)

    Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

    2018-01-01

    Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and

  17. Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

    Science.gov (United States)

    Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

    2018-01-01

    Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and

  18. Computational redesign of human respiratory syncytial virus epitope as therapeutic peptide vaccines against pediatric pneumonia.

    Science.gov (United States)

    Shi, Xiangxiang; Zheng, Jun; Yan, Tingting

    2018-03-02

    Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. Here, the RSV fusion (F) glycoprotein epitope FFL was redesigned based on its complex crystal structure with motavizumab, an mAb drug in development for the prevention of RSV infections, aiming to obtain therapeutic peptide vaccines with high affinity to induce RSV-specific neutralizing antibodies. Computational modeling and analysis found that only a small region covering the helix-turn-helix (HTH) motif of FFL can directly interact with motavizumab and confer stability and specificity to the complex system, while the rest of the epitope primarily serves as a structural scaffold that stabilizes the HTH conformation of motavizumab-binding site. Molecular dynamics simulations revealed a large flexibility and intrinsic disorder for the isolated linear HTH peptide, which would incur a considerable entropy penalty upon binding to motavizumab. In this respect, the FFL epitope was redesigned by truncation, mutation, and cyclization to derive a number of small cyclic peptide immunogens. We also employed in vitro fluorescence-based assays to demonstrate that the linear epitope peptide has no observable affinity to motavizumab, whereas redesigned versions of the peptide can bind with a moderate or high potency. Graphical abstract Computationally modeled complex structure of RSV F glycoprotein with motavizumab and zoom up of the complex binding site.

  19. Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

    Directory of Open Access Journals (Sweden)

    Wendy Fonseca

    2018-02-01

    Full Text Available Respiratory syncytial virus (RSV is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection.

  20. Antiviral effect of cimicifugin from Cimicifuga foetida against human respiratory syncytial virus.

    Science.gov (United States)

    Wang, Kuo-Chih; Chang, Jung-San; Lin, Liang-Tzung; Chiang, Lien-Chai; Lin, Chun-Ching

    2012-01-01

    Human respiratory syncytial virus (RSV) causes serious infection of the lower respiratory tract in children and an effective antiviral therapy against the viral pathogen remains unavailable. We previously demonstrated that the oriental medicinal plant, Cimicifuga foetida L. (C. foetida), possessed inhibitory activity against RSV. Since cimicifugin is a major constituent of C. foetida, we sought to examine in this study its anti-RSV effect on both the human upper (HEp-2) and lower (A549) respiratory tract cell lines. Results revealed that cimicifugin dose-dependently inhibited RSV-induced plaque formation in both HEp-2 and A549 cells (p < 0.0001), with a superior effect in the latter cell type (p < 0.0001). The antiviral activity of cimicifugin was time-dependent (p < 0.0001) and was most effective when cells were treated with the compound before viral inoculation. Additional experiments demonstrated that cimicifugin could inhibit viral attachment (p < 0.0001) and viral internalization (p < 0.0001). Furthermore, the drug could potentiate heparin's effect against attachment of RSV, particularly in A549 cells. Enzyme-linked immunosorbent assay (ELISA) analysis of antiviral cytokines induction revealed that cimicifugin could also stimulate epithelial cells to secrete IFN-β to counteract viral infection. Taken together, these results indicate that cimicifugin is an efficient antiviral agent against RSV infection. We suggest that cimicifugin might be useful for the management of RSV pathogenesis.

  1. Extensive sequence divergence among bovine respiratory syncytial viruses isolated during recurrent outbreaks in closed herds

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tjørnehøj, Kirsten; Viuff, B.

    2000-01-01

    The nucleotides coding for the extracellular part of the G glycoprotein and the full SH protein of bovine respiratory syncytial virus (BRSV) were sequenced from viruses isolated from numerous outbreaks of BRSV infection. The isolates included viruses isolated from the same herd (closed dairy farms...... and veal calf production units) in different years and from all confirmed outbreaks in Denmark within a short period. The results showed that identical viruses were isolated within a herd during outbreaks and that viruses from recurrent infections varied by up to 11% in sequence even in closed herds....... It is possible that a quasispecies variant swarm of BRSV persisted in some of the calves in each herd and that a new and different highly fit virus type (master and consensus sequence) became dominant and spread from a single animal in connection with each new outbreak. Based on the high level of diversity...

  2. Respiratory Syncytial Virus: Targeting the G Protein Provides a New Approach for an Old Problem.

    Science.gov (United States)

    Tripp, Ralph A; Power, Ultan F; Openshaw, Peter J M; Kauvar, Lawrence M

    2018-02-01

    Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) annually affecting >2 million children in the United States 65 years old), RSV results in ∼175,000 hospitalizations annually in the United States with a worldwide incidence of ∼34 million. There is no approved RSV vaccine, and treatments are limited. Recently, a phase 3 trial in the elderly using a recombinant RSV F protein vaccine failed to meet its efficacy objectives, namely, prevention of moderate-to-severe RSV-associated LRTI and reduced incidence of acute respiratory disease. Moreover, a recent phase 3 trial evaluating suptavumab (REGN2222), an antibody to RSV F protein, did not meet its primary endpoint of preventing medically attended RSV infections in preterm infants. Despite these setbacks, numerous efforts targeting the RSV F protein with vaccines, antibodies, and small molecules continue based on the commercial success of a monoclonal antibody (MAb) against the RSV F protein (palivizumab). As the understanding of RSV biology has improved, the other major coat protein, the RSV G protein, has reemerged as an alternative target reflecting progress in understanding its roles in infecting bronchial epithelial cells and in altering the host immune response. In mouse models, a high-affinity, strain-independent human MAb to the RSV G protein has shown potent direct antiviral activity combined with the alleviation of virus-induced immune system effects that contribute to disease pathology. This MAb, being prepared for clinical trials, provides a qualitatively new approach to managing RSV for populations not eligible for prophylaxis with palivizumab. Copyright © 2018 American Society for Microbiology.

  3. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

    Directory of Open Access Journals (Sweden)

    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  4. Computational Breakthrough of Natural Lead Hits from the Genus ofArisaemaagainst Human Respiratory Syncytial Virus.

    Science.gov (United States)

    Kant, Kamal; Lal, Uma Ranjan; Ghosh, Manik

    2018-01-01

    To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV. Selected 60 phytochemical entities were evaluated on the docking behavior of human RSV receptor (PDB: 4UCC) using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). Furthermore, kinetic properties and toxicity nature of top graded ligands were analyzed through QikProp and ProTox tools. Notably, rutin (glide score: -8.49), schaftoside (glide score: -8.18) and apigenin-6,8-di-C-β-D-galactoside (glide score - 7.29) have resulted in hopeful natural lead hits with an ideal range of kinetic descriptors values. ProTox tool (oral rodent toxicity) has resulted in likely toxicity targets of apex-graded tested ligands. Finally, the whole efforts can be explored further as a model to confirm its anti-human RSV potential with wet laboratory experiments. Rutin, schaftoside, and apigenin-6,8-di-C-β-D-galactoside showed promising top hits docking profile against human respiratory syncytial virusMoreover, absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptorsProTox tool highlighted toxicity class ranges, LD 50 values, and possible toxicity targets of apex-graded tested ligands. Abbreviations used: RSV: Respiratory syncytial virus, PRRSV: Porcine respiratory and reproductive syndrome virus, ADME-T: Absorption, distribution, metabolism, excretion, and toxicity.

  5. BOVINE RESPIRATORY SYNCYTIAL VIRUS EPIDEMIOLOGY AND RISK FACTORS ON CATTLE HERDS OF CAMPECHE STATE, MEXICO

    Directory of Open Access Journals (Sweden)

    Lisandro Alberto Encalada Mena

    2016-12-01

    Full Text Available High seroprevalence in Yucatan and proximity to the state of Campeche make it necessary to determine the seroprevalence and risk factors of bovine respiratory syncytial virus (VRSB in the state of Campeche, Mexico. Thus the objective of the present work was to determine the seroprevalence and risk factors bovine respiratory syncytial virus (BRSV of the state of Campeche, Mexico. The sampled of 36 cattle herds (842 sera were analyzed by indirect ELISA kit, in the 11 municipalities of Campeche. A survey to obtain risk factors (sex, age of animals, number of animals grazing density, management system, presence of sheep on the farm and access to the roadside was applied and calculated X2 for each variable considered. Of the total number of samples analyzed (842, 273 were positive (32.47%. The prevalence ranges found ranged from 0% to 84%, so in 9 of the herds there were no positive samples, indicating a 75% (27/36 of dispersion of this virus. X2 analysis indicated that all variables were significant and are risk factors regarding with respect to the variable seroprevalence of BRSV. The results indicate a wide circulation of BRSV and we suggest implement recommendations that will enable a lower spread of this virus in the cattle population.

  6. Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Ke Ni

    Full Text Available BACKGROUND: Regulatory T cells (Treg cells, which are essential for regulation of immune response to respiratory syncytial virus (RSV infection, are promoted by pharyngeal commensal pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway responsiveness and relative immune responses after RSV infection have not been clarified. METHODS: Female BALB/c mice (aged 3 weeks were infected with RSV and then treated with either oral antibiotics or oral double distilled water (ddH(2O from 1 d post infection (pi. Changes in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF were investigated in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR, pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and TGF-β1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA challenge was used to induce AHR after RSV infection. RESULTS: The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection, AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary Treg cells, Foxp3 mRNA and TGF-β1 were detected. Similar results were observed under OVA challenge. CONCLUSIONS: After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.

  7. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children

    DEFF Research Database (Denmark)

    Bisgaard, H.; Flores-Nunez, A.; Goh, A.

    2008-01-01

    RATIONALE: A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial virus...... (RSV) bronchiolitic respiratory symptoms. OBJECTIVES: To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. METHODS: This was a double-blind study of 3- to 24-month-old children who...... had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV. Patients (n = 979) were randomized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks (period I) and 20 weeks (period II). The primary end point was percentage symptom...

  8. Role of Bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia.

    Science.gov (United States)

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Subramaniam, Renuka; Herndon, Caroline N; Bavananthasivam, Jegarubee; Haldorson, Gary J; Foreyt, William J; Evermann, James F; Herrmann-Hoesing, Lynn M; Knowles, Donald P; Srikumaran, Subramaniam

    2013-02-22

    Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study, two groups of four BHS each were intra-tracheally administered with leukotoxin-positive (Group I) or leukotoxin-negative (Group II) B. trehalosi. All four animals in Group I developed severe pneumonia, and two of them died within 3 days. The other two animals showed severe pneumonic lesions on euthanasia and necropsy. Animals in Group II neither died nor showed gross pneumonic lesions on necropsy, suggesting that leukotoxin-positive, but not leukotoxin-negative, B. trehalosi can cause fatal pneumonia in BHS. In the second study, two other groups of four BHS (Groups III and IV) were intra-nasally administered with a mixture of RSV and PI-3. Four days later, RSV/PI-3-inoculated Group IV and another group of four BHS (Group V, positive control) were intra-nasally administered with Mannheimia haemolytica, the pathogen that consistently causes fatal pneumonia in BHS. All four animals in group III developed pneumonia, but did not die during the study period. However all four animals in Group IV, and three animals in Group V developed severe pneumonia and died within two days of M. haemolytica inoculation. The fourth animal in Group V showed severe pneumonic lesions on euthanasia and necropsy. These findings suggest that RSV/PI-3 can cause non-fatal pneumonia, but are not necessary predisposing agents for M. haemolytica-caused pneumonia of BHS. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Production of chemokines in respiratory syncytial virus infection with central nervous system manifestations.

    Science.gov (United States)

    Kawashima, Hisashi; Kashiwagi, Yasuyo; Ioi, Hiroaki; Morichi, Shinichiro; Oana, Shingo; Yamanaka, Gaku; Takekuma, Kouji; Hoshika, Akinori; Sawai, Jun; Kato, Yuichi

    2012-12-01

    Respiratory syncytial virus (RSV) infection in children can be associated with acute encephalopathy. However, the roles of cytokines in the cerebrospinal fluid (CSF) of such patients remain unevaluated. In this study, a profile of 17 cytokines was determined for eight RSV-infected children with neurological complications. In one patient with high levels of 13 cytokines, a cytokine storm was considered to have occurred. Interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1β levels were also high in other patients. These data suggest that chemokines in CSF play roles in neurological complications in RSV-infected children.

  10. A Case of Respiratory Syncytial Virus Infection in an HIV-Positive Adult

    Directory of Open Access Journals (Sweden)

    Aakriti Gupta

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin.

  11. Prevention and treatment of respiratory syncytial virus bronchiolitis and postbronchiolitic wheezing

    Directory of Open Access Journals (Sweden)

    Kimpen Jan LL

    2002-06-01

    Full Text Available Abstract Respiratory syncytial virus (RSV is the primary cause of hospitalization for acute respiratory tract illness in general and specifically for bronchiolitis in young children. The link between RSV bronchiolitis and reactive airway disease is not completely understood, even though RSV bronchiolitis is frequently followed by recurrent episodes of wheezing. Therapy with ribavirin does not appear to significantly reduce long-term respiratory outcome of RSV lower respiratory tract infection, and corticosteroid or bronchodilator therapy may possibly improve outcomes only on a short-term basis. No vaccine against RSV is yet available. It is not known whether prophylaxis with RSV intravenous immune globulin or palivizumab can reduce postbronchiolitic wheezing.

  12. Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Henrik Larsen, Hans; Koch, Anders

    2004-01-01

    The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p respiratory support. hMPV is present in young...

  13. Respiratory Syncytial Virus Lower Respiratory Tract Infections in Premature Infants and Infants with Bronchopulmonary Dysplasia

    Directory of Open Access Journals (Sweden)

    D. Yu. Ovsyannikov

    2015-01-01

    Full Text Available The article is devoted to the study of features of lower respiratory tract infection associated with respiratory syncytial virus. 40 cases of RSV-bronchiolitis in preterm children under year with/without bronchopulmonary dysplasia were analyzed. It was established that disease in those groups of patients had severe course because of the respiratory failure, which dominates in clinical pictures as symptoms of bronchial obstruction and apnea. Treatment of severe RSV-infection often demand admission to intensive care unit, supplemental oxygen and/or mechanical ventilation.

  14. Measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact

    DEFF Research Database (Denmark)

    Sørup, Signe; Benn, Christine Stabell; Stensballe, Lone Graff

    2015-01-01

    BACKGROUND: The live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association...... was strongest for admissions with lower respiratory infections. OBJECTIVE: To examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. METHODS: Nationwide cohort study of laboratory...

  15. [Monitoring respiratory syncytial virus through the Spanish influenza surveillance system, 2006-2014].

    Science.gov (United States)

    Jiménez-Jorge, Silvia; Delgado-Sanz, Concepción; de Mateo, Salvador; Pozo, Francisco; Casas, Inmaculada; Larrauri, Amparo

    2016-02-01

    The aim of the study is to analyze the information on respiratory syncytial virus (RSV) obtained through the Spanish Influenza Surveillance System (SISS) and to study its usefulness as supplementary information for the characterization of influenza epidemics. The temporal patterns of both RSV and influenza viruses were analyzed by patterns comparing the weekly viral detection rates from 2006 to 2014. In general, the RSV circulation was characterized by showing a peak between 52-1 weeks, and circulated from 2 to 8 weeks before/prior to influenza viruses. RSV information obtained from the SISS is useful for the characterization of influenza epidemics in Spain. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Strategic priorities for respiratory syncytial virus (RSV) vaccine development

    Science.gov (United States)

    Anderson, L.J.; Dormitzer, P.R.; Nokes, D.J.; Rappuoli, R.; Roca, A.; Graham, B.S.

    2013-01-01

    Although RSV has been a high priority for vaccine development, efforts to develop a safe and effective vaccine have yet to lead to a licensed product. Clinical and epidemiologic features of RSV disease suggest there are at least 4 distinct target populations for vaccines, the RSV naïve young infant, the RSV naïve child ≥6 months of age, pregnant women (to provide passive protection to newborns), and the elderly. These target populations raise different safety and efficacy concerns and may require different vaccination strategies. The highest priority target population is the RSV naïve child. The occurrence of serious adverse events associated with the first vaccine candidate for young children, formalin inactivated RSV (FI-RSV), has focused vaccine development for the young RSV naïve child on live virus vaccines. Enhanced disease is not a concern for persons previously primed by a live virus infection. A variety of live-attenuated viruses have been developed with none yet achieving licensure. New live-attenuated RSV vaccines are being developed and evaluated that maybe sufficiently safe and efficacious to move to licensure. A variety of subunit vaccines are being developed and evaluated primarily for adults in whom enhanced disease is not a concern. An attenuated parainfluenza virus 3 vector expressing the RSV F protein was evaluated in RSV naïve children. Most of these candidate vaccines have used the RSV F protein in various vaccine platforms including virus-like particles, nanoparticles, formulated with adjuvants, and expressed by DNA or virus vectors. The other surface glycoprotein, the G protein, has also been used in candidate vaccines. We now have tools to make and evaluate a wide range of promising vaccines. Costly clinical trials in the target population are needed to evaluate and select candidate vaccines for advancement to efficacy trials. Better data on RSV-associated mortality in developing countries, better estimates of the risk of long term

  17. Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses.

    Science.gov (United States)

    Bajimaya, Shringkhala; Frankl, Tünde; Hayashi, Tsuyoshi; Takimoto, Toru

    2017-10-01

    Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In this study, we analyzed the role of cholesterol on influenza A virus (IAV) and respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human airway cells with the agents did not decrease virus particle production. However, the released virions were less homogeneous in density and unstable. Addition of exogenous cholesterol to the released virions restored virus stability and infectivity. Collectively, these data indicate a critical role of cholesterol in maintaining IAV and RSV membrane structure that is essential for sustaining viral stability and infectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Respiratory syncytial virus infection down-regulates antioxidant enzyme expression by triggering deacetylation-proteasomal degradation of Nrf2.

    Science.gov (United States)

    Komaravelli, Narayana; Tian, Bing; Ivanciuc, Teodora; Mautemps, Nicholas; Brasier, Allan R; Garofalo, Roberto P; Casola, Antonella

    2015-11-01

    Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or treatment is available. RSV infection in cells, mice, and children leads to rapid generation of reactive oxygen species, which are associated with oxidative stress and lung damage, due to a significant decrease in the expression of airway antioxidant enzymes (AOEs). Oxidative stress plays an important role in the pathogenesis of RSV-induced lung disease, as antioxidants ameliorate clinical disease and inflammation in vivo. The aim of this study is to investigate the unknown mechanism(s) of virus-induced inhibition of AOE expression. RSV infection is shown to induce a progressive reduction in nuclear and total cellular levels of the transcription factor NF-E2-related factor 2 (Nrf2), resulting in decreased binding to endogenous AOE gene promoters and decreased AOE expression. RSV induces Nrf2 deacetylation and degradation via the proteasome pathway in vitro and in vivo. Histone deacetylase and proteasome inhibitors block Nrf2 degradation and increase Nrf2 binding to AOE endogenous promoters, resulting in increased AOE expression. Known inducers of Nrf2 are able to increase Nrf2 activation and subsequent AOE expression during RSV infection in vitro and in vivo, with significant amelioration of oxidative stress. This is the first study to investigate the mechanism(s) of virus-induced inhibition of AOE expression. RSV-induced inhibition of Nrf2 activation, due to deacetylation and proteasomal degradation, could be targeted for therapeutic intervention aimed to increase airway antioxidant capacity during infection. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Codetection of Respiratory Syncytial Virus in Habituated Wild Western Lowland Gorillas and Humans During a Respiratory Disease Outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:60077344 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: EE - Microbiology, Virology Impact factor: 2.252, year: 2016

  20. Codetection of respiratory syncytial virus in habituated wild western lowland gorillas and humans during a respiratory disease outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:68081766 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: GJ - Animal Vermins ; Disease s, Veterinary Medicine Impact factor: 2.252, year: 2016

  1. Infants with severe respiratory syncytial virus needed less ventilator time with nasal continuous airways pressure then invasive mechanical ventilation

    NARCIS (Netherlands)

    Borckink, Ilse; Essouri, Sandrine; Laurent, Marie; Albers, Marcel J. I. J.; Burgerhof, Johannes G. M.; Tissieres, Pierre; Kneyber, Martin C. J.

    AIM: Nasal continuous positive airway pressure (NCPAP) has been proposed as an early first-line support for infants with severe respiratory syncytial virus (RSV) infection. We hypothesised that infants <6 months with severe RSV would require shorter ventilator support on NCPAP than invasive

  2. Safety and immunogenicity of a novel recombinant subunit respiratory syncytial virus vaccine (BBG2Na) in healthy young adults

    NARCIS (Netherlands)

    U.F. Power; T.N. Nguyen; E. Rietveld (Edwin); R.L. de Swart (Rik); J.M. Groen (Jan); A.D.M.E. Osterhaus (Albert); R. de Groot (Ronald); N. Corvaia; A. Beck (Alain); N. Bouveret-le-Cam; J-Y. Bonnefoy

    2001-01-01

    textabstractA novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 μg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of

  3. GENETIC SUSCEPTIBILITY TO RESPIRATORY SYNCYTIAL VIRUS BRONCHIOLITIS IN PRETERM CHILDREN IS ASSOCIATED WITH AIRWAY REMODELING GENES AND INNATE IMMUNE GENES

    NARCIS (Netherlands)

    Siezen, Christine L. E.; Bont, Louis; Hodemaekers, Hennie M.; Ermers, Marieke J.; Doornbos, Gerda; van't Slot, Ruben; Wijmenga, Ciska; van Hottwelingen, Hans C.; Kimpen, Jan L. L.; Kimman, Tjeerd G.; Hoebee, Barbara; Janssen, Riny

    Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2. IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease

  4. FC GAMMA RECEPTORS IN RESPIRATORY SYNCYTIAL VIRUS INFECTIONS: IMPLICATIONS FOR INNATE IMMUNITY

    Science.gov (United States)

    Jans, Jop; Vissers, Marloes; Heldens, Jacco G.M.; de Jonge, Marien I.; Levy, Ofer; Ferwerda, Gerben

    2014-01-01

    SUMMARY Respiratory syncytial virus infections are a major burden in infants less than 3 months of age. Newborns and infants express a distinct immune system that is largely dependent on innate immunity and passive immunity from maternal antibodies. Antibodies can regulate immune responses against viruses through interaction with Fc gamma receptors leading to enhancement or neutralization of viral infections. The mechanisms underlying the immunomodulatory effect of Fc gamma receptors on viral infections have yet to be elucidated in infants. Herein, we will discuss current knowledge of the effects of antibodies and Fc gamma receptors on infant innate immunity to RSV. A better understanding of the pathogenesis of RSV infections in young infants may provide insight into novel therapeutic strategies like vaccination. PMID:24227634

  5. Comparison of rapid immunofluorescence procedure with TestPack RSV and Directigen FLU-A for diagnosis of respiratory syncytial virus and influenza A virus.

    OpenAIRE

    Todd, S J; Minnich, L; Waner, J L

    1995-01-01

    A rapid immunofluorescence format requiring 20 min for completion was as effective as conventional indirect and direct immunofluorescence procedures for detecting respiratory syncytial virus and influenza A virus antigens in clinical specimens. Rapid immunofluorescence was more sensitive than TestPack RSV and comparable to Directigen FLU-A immunosorbent assays, which require 20 min for completion.

  6. New respiratory virus (chicken pox, influenza and respiratory syncytial virus) vaccines: efficacy, necessity and policy for the tropical world at present.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2009-09-01

    Several respiratory viruses are documented in medicine. Several infectious diseases due to these viruses are current global public health problems. Prevention of respiratory viral infections becomes the focus of the public health ministries of many tropical countries. Presently, there are many new vaccines for respiratory viruses. These vaccines include chicken pox vaccine, influenza vaccine and respiratory syncytial virus vaccine. In this article, the author will briefly discuss on these quoted vaccines focusing on efficacy, necessity and policy for tropical world at present.

  7. Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Boyington

    Full Text Available Respiratory syncytial virus (RSV is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F surface glycoprotein-stabilized in the pre-fusion (pre-F conformation by "DS-Cav1" mutations-elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These "head-only" immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent

  8. Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Young J. Lee

    2018-01-01

    Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

  9. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus.

    Directory of Open Access Journals (Sweden)

    Eleanor R Gaunt

    2011-03-01

    Full Text Available Human respiratory syncytial virus (HRSV and human metapneumovirus (HMPV are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F protein, and the extremely diverse attachment (G glycoprotein. Both viruses comprise two genetic groups, A and B. Circulation frequencies of the two genetic groups fluctuate for both viruses, giving rise to frequently observed switching of the predominantly circulating group. Nucleotide sequence data for the F and G gene regions of HRSV and HMPV variants from the UK, The Netherlands, Bangkok and data available from Genbank were used to identify clades of both viruses. Several contemporary circulating clades of HRSV and HMPV were identified by phylogenetic reconstructions. The molecular epidemiology and evolutionary dynamics of clades were modelled in parallel. Times of origin were determined and positively selected sites were identified. Sustained circulation of contemporary clades of both viruses for decades and their global dissemination demonstrated that switching of the predominant genetic group did not arise through the emergence of novel lineages each respiratory season, but through the fluctuating circulation frequencies of pre-existing lineages which undergo proliferative and eclipse phases. An abundance of sites were identified as positively selected within the G protein but not the F protein of both viruses. For HRSV, these were discordant with previously identified residues under selection, suggesting the virus can evade immune responses by generating diversity at multiple sites within linear epitopes. For both viruses, different sites were identified as positively selected between genetic groups.

  10. Crucial roles of reactive chemical species in modification of respiratory syncytial virus by nitrogen gas plasma.

    Science.gov (United States)

    Sakudo, Akikazu; Toyokawa, Yoichi; Imanishi, Yuichiro; Murakami, Tomoyuki

    2017-05-01

    The exact mechanisms by which nanoparticles, especially those composed of soft materials, are modified by gas plasma remain unclear. Here, we used respiratory syncytial virus (RSV), which has a diameter of 80-350nm, as a model system to identify important factors for gas plasma modification of nanoparticles composed of soft materials. Nitrogen gas plasma, generated by applying a short high-voltage pulse using a static induction (SI) thyristor power supply produced reactive chemical species (RCS) and caused virus inactivation. The plasma treatment altered the viral genomic RNA, while treatment with a relatively low concentration of hydrogen peroxide, which is a neutral chemical species among RCS, effectively inactivated the virus. Furthermore, a zero dimensional kinetic global model of the reaction scheme during gas plasma generation identified the production of various RCS, including neutral chemical species. Our findings suggest the nitrogen gas plasma generates RCS, including neutral species that damage the viral genomic RNA, leading to virus inactivation. Thus, RCS generated by gas plasma appears to be crucial for virus inactivation, suggesting this may constitute an important factor in terms of the efficient modification of nanoparticles composed of soft materials. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    International Nuclear Information System (INIS)

    Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J.

    2015-01-01

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function

  12. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    Energy Technology Data Exchange (ETDEWEB)

    Jumat, Muhammad Raihan [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Yan, Yan [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Ravi, Laxmi Iyer [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Wong, Puisan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Huong, Tra Nguyen [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Li, Chunwei [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Tan, Boon Huan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Wang, De Yun [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Sugrue, Richard J., E-mail: rjsugrue@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)

    2015-10-15

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

  13. Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection

    Science.gov (United States)

    Do, Lien Anh Ha; Pellet, Johann; van Doorn, H Rogier; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Nguyen, Huu Mai Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; De Meulder, Bertrand; Auffray, Charles; Hofstra, Jorrit-Jan; Farrar, Jeremy; Bryant, Juliet E; de Jong, Menno; Hibberd, Martin L

    2018-01-01

    Abstract Background Most insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. Methods In this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalized patients <2 years old with lower respiratory tract infections. Results Respiratory syncytial virus infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon-α/β, NOTCH1 signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples, or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were associated with both RSV load and severity. The observed RSV-induced gene expression patterns did not differ significantly in NP swab and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP swab and blood specimens. Conclusions We conclude that RSV induced strong and persistent innate immune responses and that RSV severity may be related to development of T follicular helper cells and antiviral inflammatory sequelae derived from high activation of BCL6. PMID:29029245

  14. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection

    Science.gov (United States)

    Yang, Xiao Xi; Li, Chun Mei; Huang, Cheng Zhi

    2016-01-01

    Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concentration of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition

  15. A Decade of Respiratory Syncytial Virus Epidemiology and Prophylaxis: Translating Evidence into Everyday Clinical Practice

    Directory of Open Access Journals (Sweden)

    Bosco A Paes

    2011-01-01

    Full Text Available Respiratory syncytial virus (RSV is a common infection in infancy, with nearly all children affected by two years of age. Approximately 0.5% to 2.0% of all children are hospitalized with lower respiratory tract disease, of which 50% to 90% have bronchiolitis and 5% to 40% have pneumonia. Morbidity and mortality are highest in children with nosocomial infection and in those with underlying medical illnesses such as cardiac and chronic lung disease. Aboriginal children residing in remote northern regions are specifically considered to be at high risk for hospitalization due to RSV infection. Thorough hand washing and health education are the principal strategies in primary prevention. In the absence of a vaccine, palivizumab prophylaxis is currently the best intervention to reduce the burden of illness and RSV-related hospitalization in high-risk children. Health care professionals should provide palivizumab prophylaxis cost effectively in accordance with recommendations issued by pediatric societies and national advisory bodies.

  16. Systemic signature of the lung response to respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Jeroen L A Pennings

    Full Text Available Respiratory Syncytial Virus is a frequent cause of severe bronchiolitis in children. To improve our understanding of systemic host responses to RSV, we compared BALB/c mouse gene expression responses at day 1, 2, and 5 during primary RSV infection in lung, bronchial lymph nodes, and blood. We identified a set of 53 interferon-associated and innate immunity genes that give correlated responses in all three murine tissues. Additionally, we identified blood gene signatures that are indicative of acute infection, secondary immune response, and vaccine-enhanced disease, respectively. Eosinophil-associated ribonucleases were characteristic for the vaccine-enhanced disease blood signature. These results indicate that it may be possible to distinguish protective and unfavorable patient lung responses via blood diagnostics.

  17. A Two-Dimensional Human Minilung System (Model for Respiratory Syncytial Virus Infections

    Directory of Open Access Journals (Sweden)

    Esmeralda Magro-Lopez

    2017-12-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of serious pediatric respiratory diseases that lacks effective vaccine or specific therapeutics. Although our understanding about HRSV biology has dramatically increased during the last decades, the need for adequate models of HRSV infection is compelling. We have generated a two-dimensional minilung from human embryonic stem cells (hESCs. The differentiation protocol yielded at least six types of lung and airway cells, although it is biased toward the generation of distal cells. We show evidence of HRSV replication in lung cells, and the induction of innate and proinflammatory responses, thus supporting its use as a model for the study of HRSV–host interactions.

  18. Clinical perspectives on the association between respiratory syncytial virus and reactive airway disease

    Directory of Open Access Journals (Sweden)

    Sigurs Nele

    2002-06-01

    Full Text Available Abstract Asthma is a leading cause of morbidity and mortality among children worldwide, as is respiratory syncytial virus (RSV. This report reviews controlled retrospective and prospective studies conducted to investigate whether there is an association between RSV bronchiolitis in infancy and subsequent development of reactive airway disease or allergic sensitization. Findings indicate that such a link to bronchial obstructive symptoms does exist and is strongest for children who experienced severe RSV illness that requires hospitalization. However, it is not yet clear what roles genetic predisposition and environmental or other risk factors may play in the interaction between RSV bronchiolitis and reactive airway disease or allergic sensitization. Randomized, prospective studies utilizing an intervention against RSV, such as a passive immunoprophylactic agent, may determine whether preventing RSV bronchiolitis reduces the incidence of asthma.

  19. The causal direction in the association between respiratory syncytial virus hospitalization and asthma

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Simonsen, Jacob Brunbjerg; Thomsen, Simon Francis

    2009-01-01

    BACKGROUND: Earlier studies have reported an increased risk of asthma after respiratory syncytial virus (RSV) hospitalization. Other studies found that asthmatic disposition and propensity to wheeze increase the risk of RSV hospitalization. OBJECTIVE: The current study examined the causal direction...... of the associations between RSV hospitalization and asthma in a population-based cohort of twins. METHODS: We conducted a prospective cohort study examining the associations between RSV hospitalization and asthma by using registry information on RSV hospitalization and asthma among 18,614 Danish twins born 1994...... to 2003. The associations between RSV and asthma were examined in both directions: we examined the risk of asthma after RSV hospitalization, and the risk of RSV hospitalization in children with asthma in the same population-based cohort. RESULTS: Asthma hospitalization after RSV hospitalization...

  20. Trends of Respiratory Syncytial Virus Infections in Children under 2 Years of Age in Puerto Rico.

    Science.gov (United States)

    Matías, Israel; García, Inés; García-Fragoso, Lourdes; Puig, Gilberto; Pedraza, Lourdes; Rodríguez, Luis; Santaella, Alvaro; Arce, Sylvia; Toledo, Marilyn; Soto, Edwin; Valcárcel, Marta

    2015-06-01

    The respiratory syncytial virus (RSV) is the most significant viral pathogen causing bronchiolitis and pneumonia in infants, today. In tropical climates the RSV infection may occur throughout the year. The purpose of this study was to asses RSV infections during the 2009‒2010 RSV season in children under 2 years of age and to evaluate the trend of positive RSV tests in the period of 2007 to 2009. A retrospective review of data collected from 6 hospitals in Puerto Rico was performed. Patients with confirmed RSV bronchiolitis were included in the study. A total of 4,678 patients were included. The mean age of the patients was 7 months. Data showed that RSV infection occurred throughout the studied months. Data confirms a year-round presence of RSV in Puerto Rico. The RSV surveillance system needs to be reinforced to establish and understand the epidemiology of RSV and to review the current immunoprophylaxis guidelines.

  1. Risk factors for respiratory syncytial virus hospitalisation in children with heart disease

    DEFF Research Database (Denmark)

    Kristensen, Kim; Stensballe, LG; Fisker, Niels

    2009-01-01

    OBJECTIVE: To assess the risk and risk factors for respiratory syncytial virus (RSV) hospitalisation and determinants of the severity of RSV disease in children with heart disease. METHODS: By using a database on RSV tests in Denmark all children with RSV diagnosed with heart disease in Denmark...... from January 1996 to April 2003 were identified. For each case child one control child matched for age and centre was drawn from the population of children with heart disease. Clinical information was obtained through a review of all records. RESULTS: Data were obtained on 313 pairs. Median age...... hospitalisation predictors of the need for respiratory support (supplemental oxygen, nasal continuous positive airway pressure or mechanical ventilation) were young age (relative risk (RR) 0.47, 95% CI 0.32 to 0.67 per additional year of age) and cardiac decompensation (RR 1.81, 95% CI 1.02 to 3...

  2. Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia—Implications for Vaccine Design

    Directory of Open Access Journals (Sweden)

    Emma Rey-Jurado

    2017-03-01

    Full Text Available The human respiratory syncytial virus (hRSV is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus.

  3. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders

    Science.gov (United States)

    Prifert, Christiane; Wedde, Marianne; Puthenparambil, Joe; Weissbrich, Benedikt; Biere, Barbara; Schweiger, Brunhilde; Egerer, Gerlinde; Schnitzler, Paul

    2016-01-01

    Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17%) were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111) underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic). LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1)pdm09, A(H3N2), influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75%) of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01) and was most pronounced in patients with RSV infection (n = 16) with a median duration of viral shedding for 80 days (range 35–334 days). Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

  4. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders.

    Directory of Open Access Journals (Sweden)

    Nicola Lehners

    Full Text Available Respiratory viruses are a cause of upper respiratory tract infections (URTI, but can be associated with severe lower respiratory tract infections (LRTI in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17% were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111 underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic. LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1pdm09, A(H3N2, influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75% of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01 and was most pronounced in patients with RSV infection (n = 16 with a median duration of viral shedding for 80 days (range 35-334 days. Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

  5. A single vaccination with an inactivated bovine respiratory syncytial virus vaccine primes the cellular immune response in calves with maternal antibody

    Directory of Open Access Journals (Sweden)

    Makoschey Birgit

    2010-01-01

    Full Text Available Abstract Background The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (BRSV - Parainfluenaza type 3 (PI3 - Mannheimia haemolytica (Mh combination vaccine, in calves positive for maternal antibodies, was established in a BRSV infection study. Results As expected the single vaccination did not have any effect on the decline of BRSV-specific neutralising or ELISA antibody. The cellular immune system was however primed by the vaccination. In the vaccinated group virus excretion with nasal discharge was reduced, less virus could be re-isolated from lung tissues and the lungs were less affected. Conclusions These results indicate that a single vaccination with an inactivated BRSV vaccine was able to break through the maternal immunity and induce partial protection in very young calves. It can be speculated that the level and duration of protection will improve after the second dose of vaccine is administered. A two-dose basic vaccination schedule is recommended under field conditions.

  6. Detection of an untyped strain of bovine respiratory syncytial virus in a dairy herd

    Directory of Open Access Journals (Sweden)

    Ingrid Bortolin Affonso

    2014-10-01

    Full Text Available Bovine respiratory syncytial virus (BRSV causes important lower respiratory tract illness in calves. According to F and G proteins genetic sequences, three BRSV subgroups have been reported and characterized in several countries, showing differences in its distribution. In Brazil, the virus is widely disseminated throughout the herds and the few characterized isolates revealed the solely occurrence of the subgroup B. This study describes the detection and characterization of an untyped BRSV strain from a twenty-days-old calf from a herd without clinical respiratory disease. Nasal swabs were analyzed by RT-nested PCR for the F and G proteins genes. One sample has amplified the F protein gene. Sequencing and subsequent phylogenetic reconstruction were accomplished, revealing that the strain could not be grouped with any other BRSV subgroups reported. This result may suggest that the BRSV is in constantly evolution, even in Brazil, where the vaccination is not a common practice. More detailed studies about BRSV characterization are necessary to know the virus subgroups distribution among the Brazilian herds to recommend appropriated immunoprophylaxis.

  7. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating

    International Nuclear Information System (INIS)

    Asenjo, Ana; Gonzalez-Armas, Juan C.; Villanueva, Nieves

    2008-01-01

    The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) β and protein phosphatase 2A (PP2A). Inhibition of lithium-sensitive kinase, soon after infection, blocks the viral growth cycle by inhibiting synthesis and/or accumulation of viral RNAs, proteins and extracellular particles. P protein phosphorylation at S54 is required to liberate viral ribonucleoproteins (RNPs) from M protein, during the uncoating process. Kinase inhibition, late in infection, produces a decrease in genomic RNA and infectious viral particles. LiCl, intranasally applied to mice infected with HRSV A2 strain, reduces the number of mice with virus in their lungs and the virus titre. Administration of LiCl to humans via aerosol should prevent HRSV infection, without secondary effects

  8. Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

    Science.gov (United States)

    Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

    2017-11-02

    Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

  9. Ameliorating Effect of Dietary Xylitol on Human Respiratory Syncytial Virus (hRSV) Infection.

    Science.gov (United States)

    Xu, Mei Ling; Wi, Ga Ram; Kim, Hyoung Jin; Kim, Hong-Jin

    2016-01-01

    Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in infants. The lack of proper prophylactics and therapeutics for controlling hRSV infection has been of great concern worldwide. Xylitol is a well-known sugar substitute and its effect against bacteria in the oral cavity is well known. However, little is known of its effect on viral infections. In this study, the effect of dietary xylitol on hRSV infection was investigated in a mouse model for the first time. Mice received xylitol for 14 d prior to virus challenge and for a further 3 d post challenge. Significantly larger reductions in lung virus titers were observed in the mice receiving xylitol than in the controls receiving phosphate-buffered saline (PBS). In addition, fewer CD3(+) and CD3(+)CD8(+) lymphocytes, whose numbers reflect inflammatory status, were recruited in the mice receiving xylitol. These results indicate that dietary xylitol can ameliorate hRSV infections and reduce inflammation-associated immune responses to hRSV infection.

  10. Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge

    NARCIS (Netherlands)

    Antonis, A.F.G.; Most, van der R.G.; Suezer, Y.; Stockhofe-Zurwieden, N.; Daus, F.J.; Sutter, G.; Schrijver, R.S.

    2007-01-01

    Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and calves. Bovine RSV (bRSV) is a natural pathogen for cattle, and bRSV infection in calves shares many features with the human infection. Thus, bRSV infection in cattle provides the ideal setting to

  11. Virus-like particle vaccines containing F or F and G proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats.

    Science.gov (United States)

    Hwang, Hye Suk; Kim, Ki-Hye; Lee, Youri; Lee, Young-Tae; Ko, Eun-Ju; Park, SooJin; Lee, Jong Seok; Lee, Byung-Cheol; Kwon, Young-Man; Moore, Martin L; Kang, Sang-Moo

    2017-05-04

    Vaccine-enhanced disease has been a major obstacle in developing a safe vaccine against respiratory syncytial virus (RSV). This study demonstrates the immunogenicity, efficacy, and safety of virus-like particle (VLP) vaccines containing RSV F (F VLP), G (G VLP), or F and G proteins (FG VLP) in cotton rats. RSV specific antibodies were effectively induced by vaccination of cotton rats with F VLP or FG VLP vaccines. After challenge, lung RSV clearance was observed with RSV F, G, FG VLP, and formalin inactivated RSV (FI-RSV) vaccines. Upon RSV infection, cotton rats with RSV VLP vaccines were protected against airway hyper-responsiveness and weight loss, which are different from FI-RSV vaccination exhibiting vaccine-enhanced disease of airway obstruction, weight loss, and severe histopathology with eosinophilia and mucus production. FG VLP and F VLP vaccines did not cause pulmonary inflammation whereas G VLP induced moderate lung inflammation with eosinophilia and mucus production. In particular, F VLP and FG VLP vaccines were found to be effective in inducing antibody secreting cell responses in bone marrow and lymphoid organs as well as avoiding the induction of T helper type 2 cytokines. These results provide further evidence to develop a safe RSV vaccine based on VLP platforms.

  12. Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants.

    Science.gov (United States)

    Sacco, Randy E; McGill, Jodi L; Palmer, Mitchell V; Lippolis, John D; Reinhardt, Timothy A; Nonnecke, Brian J

    2012-12-01

    Respiratory syncytial virus (RSV) is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of calves with bovine RSV shares features in common with RSV infection in children, such as an age-dependent susceptibility. In addition, comparable microscopic lesions consisting of bronchiolar neutrophilic infiltrates, epithelial cell necrosis, and syncytial cell formation are observed. Further, our studies have shown an upregulation of pro-inflammatory mediators in RSV-infected calves, including IL-12p40 and CXCL8 (IL-8). This finding is consistent with increased levels of IL-8 observed in children with RSV bronchiolitis. Since rodents lack IL-8, neonatal calves can be useful for studies of IL-8 regulation in response to RSV infection. We have recently found that vitamin D in milk replacer diets can be manipulated to produce calves differing in circulating 25-hydroxyvitamin D3. The results to date indicate that although the vitamin D intracrine pathway is activated during RSV infection, pro-inflammatory mediators frequently inhibited by the vitamin D intacrine pathway in vitro are, in fact, upregulated or unaffected in lungs of infected calves. This review will summarize available data that provide parallels between bovine RSV infection in neonatal calves and human RSV in infants.

  13. Neonatal Calf Infection with Respiratory Syncytial Virus: Drawing Parallels to the Disease in Human Infants

    Directory of Open Access Journals (Sweden)

    Timothy A. Reinhardt

    2012-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most common viral cause of childhood acute lower respiratory tract infections. It is estimated that RSV infections result in more than 100,000 deaths annually worldwide. Bovine RSV is a cause of enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV plays a significant role in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Infection of calves with bovine RSV shares features in common with RSV infection in children, such as an age-dependent susceptibility. In addition, comparable microscopic lesions consisting of bronchiolar neutrophilic infiltrates, epithelial cell necrosis, and syncytial cell formation are observed. Further, our studies have shown an upregulation of pro-inflammatory mediators in RSV-infected calves, including IL-12p40 and CXCL8 (IL-8. This finding is consistent with increased levels of IL-8 observed in children with RSV bronchiolitis. Since rodents lack IL-8, neonatal calves can be useful for studies of IL-8 regulation in response to RSV infection. We have recently found that vitamin D in milk replacer diets can be manipulated to produce calves differing in circulating 25-hydroxyvitamin D3. The results to date indicate that although the vitamin D intracrine pathway is activated during RSV infection, pro-inflammatory mediators frequently inhibited by the vitamin D intacrine pathway in vitro are, in fact, upregulated or unaffected in lungs of infected calves. This review will summarize available data that provide parallels between bovine RSV infection in neonatal calves and human RSV in infants.

  14. Exploring the association between severe respiratory syncytial virus infection and asthma: a registry-based twin study

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; van der Sluis, Sophie; Stensballe, Lone G

    2009-01-01

    RATIONALE: Severe respiratory syncytial virus (RSV) infection is associated with asthma but the nature of this association is imperfectly understood. OBJECTIVES: To examine the nature of the association between severe RSV infection and asthma in a population-based sample of twins. METHODS: Data......" RSV hospitalization fitted the data significantly better (P = 0.39 for deterioration in model fit) than a model in which RSV hospitalization "causes" asthma (P accounted for. CONCLUSIONS...

  15. Clinical performance evaluation of the Sofia RSV FIA rapid antigen test for diagnosis of respiratory syncytial virus infection.

    Science.gov (United States)

    Jang, Jin Woo; Cho, Chi Hyun; Nam, Myung-Hyun; Yoon, Soo Young; Lee, Chang Kyu; Lim, Chae Seung; Kim, Woo Joo

    2015-02-01

    A recently introduced Sofia respiratory syncytial virus (RSV) fluorescent immunoassay (FIA) was evaluated against the BinaxNOW RSV card and the SD Bioline RSV test using 348 respiratory samples. The Sofia, BinaxNOW, and SD Bioline kits showed sensitivities of 66%, 65%, and 64%, respectively, for detecting RSV-A, and 71%, 63%, and 65% for detecting RSV-B, respectively. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Evidence that the respiratory syncytial virus polymerase complex associates with lipid rafts in virus-infected cells: a proteomic analysis

    International Nuclear Information System (INIS)

    McDonald, Terence P.; Pitt, Andrew R.; Brown, Gaie; Rixon, Helen W. McL.; Sugrue, Richard J.

    2004-01-01

    The interaction between the respiratory syncytial virus (RSV) polymerase complex and lipid rafts was examined in HEp2 cells. Lipid-raft membranes were prepared from virus-infected cells and their protein content was analysed by Western blotting and mass spectrometry. This analysis revealed the presence of the N, P, L, M2-1 and M proteins. However, these proteins appeared to differ from one another in their association with these structures, with the M2-1 protein showing a greater partitioning into raft membranes compared to that of the N, P or M proteins. Determination of the polymerase activity profile of the gradient fractions revealed that 95% of the detectable viral enzyme activity was associated with lipid-raft membranes. Furthermore, analysis of virus-infected cells by confocal microscopy suggested an association between these proteins and the raft-lipid, GM1. Together, these results provide evidence that the RSV polymerase complex is able to associate with lipid rafts in virus-infected cells

  17. A dynamic cell entry pathway of respiratory syncytial virus revealed by tracking the quantum dot-labeled single virus.

    Science.gov (United States)

    Zheng, Lin Ling; Li, Chun Mei; Zhen, Shu Jun; Li, Yuan Fang; Huang, Cheng Zhi

    2017-06-14

    Studying the cell entry pathway at the single-particle level can provide detailed and quantitative information for the dynamic events involved in virus entry. Indeed, the viral entry dynamics cannot be monitored by static staining methods used in cell biology, and thus virus dynamic tracking could be useful in the development of effective antiviral strategies. Therefore, the aim of this work was to use a quantum dot-based single-particle tracking approach to monitor the cell entry behavior of the respiratory syncytial virus (RSV) in living cells. The time-lapse fluorescence imaging and trajectory analysis of the quantum dot-labeled RSV showed that RSV entry into HEp-2 cells consisted of a typical endocytosis trafficking process. Three critical events during RSV entry were observed according to entry dynamic and fluorescence colocalization analysis. Firstly, RSV was attached to lipid rafts of the cell membrane, and then it was efficiently delivered into the perinuclear region within 2 h post-infection, mostly moving and residing into the lysosome compartment. Moreover, the relatively slow velocity of RSV transport across the cytoplasm and the formation of the actin tail indicated actin-based RSV motility, which was also confirmed by the effects of cytoskeletal inhibitors. Taken together, these findings provided new insights into the RSV entry mechanism and virus-cell interactions in RSV infection that could be beneficial in the development of antiviral drugs and vaccines.

  18. Parainfluenza-3 and bovine respiratory syncytial virus: intraherd correlation adjusted for sensitivity and specificity

    Directory of Open Access Journals (Sweden)

    José Segura C.

    2013-11-01

    Full Text Available Objective. The purpose of this study was to compare the intra-class correlation coefficients (ICC and design effects (D estimates adjusted or unadjusted for sensibility (Se and specificity (Sp of the diagnostic tests using a Bayesian procedure. Materials and methods. Sera from 232 animals from 44 randomly selected herds, to detect antibodies against parainfluenza-3 virus (PIV3 from non-vaccinated dual-purpose cattle from Colima Mexico, were used. Only 176 animals from 33 herds were used to evaluate the presence of the bovine respiratory syncytial virus (BRSV. Results. The ICC and D values adjusted and unadjusted for PIV3 were 0.33, 2.73, 0.32, and 2.71, respectively. For BRSV the values were 0.31, 2.64, 0.28 and 2.49. Conclusions. The adjusted or unadjusted ICC and D estimates were similar because of the high Se and Sp of the diagnostic tests and the relatively high prevalence of the diseases here studied.

  19. Vertical transmission of respiratory syncytial virus modulates pre- and postnatal innervation and reactivity of rat airways.

    Directory of Open Access Journals (Sweden)

    Giovanni Piedimonte

    Full Text Available Environmental exposure to respiratory syncytial virus (RSV is a leading cause of respiratory infections in infants, but it remains unknown whether this infection is transmitted transplacentally from the lungs of infected mothers to the offspring. We sought to test the hypothesis that RSV travels from the respiratory tract during pregnancy, crosses the placenta to the fetus, persists in the lung tissues of the offspring, and modulates pre- and postnatal expression of growth factors, thereby predisposing to airway hyperreactivity.Pregnant rats were inoculated intratracheally at midterm using recombinant RSV expressing red fluorescent protein (RFP. Viral RNA was amplified by RT-PCR and confirmed by sequencing. RFP expression was analyzed by flow cytometry and viral culture. Developmental and pathophysiologic implications of prenatal infection were determined by analyzing the expression of genes encoding critical growth factors, particularly neurotrophic factors and receptors. We also measured the expression of key neurotransmitters and postnatal bronchial reactivity in vertically infected lungs, and assessed their dependence on neurotrophic signaling using selective biological or chemical inhibition.RSV genome was found in 30% of fetuses, as well as in the lungs of 40% of newborns and 25% of adults. RFP expression was also shown by flow cytometry and replicating virus was cultured from exposed fetuses. Nerve growth factor and its TrkA receptor were upregulated in RSV- infected fetal lungs and co-localized with increased cholinergic innervation. Acetylcholine expression and smooth muscle response to cholinergic stimulation increased in lungs exposed to RSV in utero and reinfected after birth, and blocking TrkA signaling inhibited both effects.Our data show transplacental transmission of RSV from mother to offspring and persistence of vertically transmitted virus in lungs after birth. Exposure to RSV in utero is followed by dysregulation of

  20. The association between serological titers in infectious bovine rhinotracheitis virus, bovine virus diarrhea virus, parainfluenza-3 virus, respiratory syncytial virus and treatment for respiratory disease in Ontario feedlot calves.

    OpenAIRE

    Martin, S W; Bohac, J G

    1986-01-01

    A seroepidemiological study of the association between antibody titers to infectious bovine rhinotracheitis, parainfluenza-3, bovine virus diarrhea and bovine respiratory syncytial viruses, and treatment for bovine respiratory disease was conducted. A total of 322 calves from five different groups were bled on arrival, then one month later all cases (cattle treated for bovine respiratory disease) were rebled together with an equal number of controls (cattle not treated for any disease). Titer...

  1. Independent lung ventilation in a newborn with asymmetric acute lung injury due to respiratory syncytial virus: a case report

    Directory of Open Access Journals (Sweden)

    Di Nardo Matteo

    2008-06-01

    Full Text Available Abstract Introduction Independent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients. Case presentation We present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weight who had an asymmetric lung injury due to respiratory syncytial virus bronchiolitis. We used independent lung ventilation applying conventional protective pressure controlled ventilation to the less-compromised lung, with a respiratory frequency proportional to the age of the patient, and a pressure controlled high-frequency ventilation to the atelectatic lung. This was done because a single tube conventional ventilation protective strategy would have exposed the less-compromised lung to a high mean airways pressure. The target of independent lung ventilation is to provide adequate gas exchange at a safe mean airways pressure level and to expand the atelectatic lung. Independent lung ventilation was accomplished for 24 hours. Daily chest radiograph and gas exchange were used to evaluate the efficacy of independent lung ventilation. Extubation was performed after 48 hours of conventional single-tube mechanical ventilation following independent lung ventilation. Conclusion This case report demonstrates the feasibility of independent lung ventilation with two separate tubes in neonates as a treatment of an asymmetric acute lung injury.

  2. The UL21 Tegument Protein of Herpes Simplex Virus 1 Is Differentially Required for the Syncytial Phenotype.

    Science.gov (United States)

    Sarfo, Akua; Starkey, Jason; Mellinger, Erica; Zhang, Dan; Chadha, Pooja; Carmichael, Jillian; Wills, John W

    2017-11-01

    The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20 Syn and UL24 Syn To test whether UL21 is needed only for the A855V mutant, additional gB Syn derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gB Syn phenotype. This is the first example of a differential requirement for a viral protein across the four syn loci. IMPORTANCE UL21 is conserved among alphaherpesviruses, but its role is poorly understood. This study shows that HSV-1 can replicate without UL21, although the virus titers are greatly reduced. The null virus had greater proportions of empty (DNA-less) capsids in the cytoplasm of infected cells, suggesting that UL21 may play a role in retaining them in the nucleus. This is consistent with reports showing UL21

  3. Molecular epidemiology of human respiratory syncytial virus over three consecutive seasons in Latvia.

    Science.gov (United States)

    Balmaks, Reinis; Ribakova, Irina; Gardovska, Dace; Kazaks, Andris

    2014-11-01

    Lower respiratory tract infections caused by the human respiratory syncytial virus (HRSV) represent an immense burden of the disease, especially in young children. This study aimed to investigate the evolutionary history of HRSV strains isolated in the Children's Clinical University Hospital (Riga, Latvia) over three consecutive HRSV seasons. Of 207 samples from children hospitalized with lower respiratory tract infections, 88 (42.5%) tested positive for HRSV by RT-PCR. The seasonal activity started and peaked later than the average for the Northern hemisphere. Patients with HRSV lower respiratory tract infection were significantly younger than patients not infected with HRSV. HRSV-A viruses predominated for two consecutive seasons and were followed by an HRSV-B dominant season. Phylogenetic analysis based on glycoprotein G gene partial sequences revealed that viruses of both groups belonged to the worldwide dominant genotypes NA1 (HRSV-A) and BA-IV (HRSV-B). High diversity of this gene was driven only partially by selection pressure, as only two positively selected sites were identified in each group. Two of the HRSV-A isolates in this study contained a 72-nt duplication in the C-terminal end of the G gene (genotype ON1) that was first described in Canada in the 2010-2011 season. Initial spatial and temporal dynamics of this novel genotype were reconstructed by discrete phylogeographic analysis. Fifteen years after acquiring comparable 60-nt duplication in the G gene, genotype BA lineages have replaced all other HRSV-B strains. However, the population size of genotype ON1 plateaued soon and even decreased slightly before the beginning of the 2012-2013 season. © 2013 Wiley Periodicals, Inc.

  4. Occurrence and phylogenetic analysis of bovine respiratory syncytial virus in outbreaks of respiratory disease in Norway.

    Science.gov (United States)

    Klem, Thea B; Rimstad, Espen; Stokstad, Maria

    2014-01-14

    Bovine respiratory syncytial virus (BRSV) is one of the major pathogens involved in the bovine respiratory disease (BRD) complex. The seroprevalence to BRSV in Norwegian cattle herds is high, but its role in epidemics of respiratory disease is unclear. The aims of the study were to investigate the etiological role of BRSV and other respiratory viruses in epidemics of BRD and to perform phylogenetic analysis of Norwegian BRSV strains. BRSV infection was detected either serologically and/or virologically in 18 (86%) of 21 outbreaks and in most cases as a single viral agent. When serology indicated that bovine coronavirus and/or bovine parainfluenza virus 3 were present, the number of BRSV positive animals in the herd was always higher, supporting the view of BRSV as the main pathogen. Sequencing of the G gene of BRSV positive samples showed that the current circulating Norwegian BRSVs belong to genetic subgroup II, along with other North European isolates. One isolate from an outbreak in Norway in 1976 was also investigated. This strain formed a separate branch in subgroup II, clearly different from the current Scandinavian sequences. The currently circulating BRSV could be divided into two different strains that were present in the same geographical area at the same time. The sequence variations between the two strains were in an antigenic important part of the G protein. The results demonstrated that BRSV is the most important etiological agent of epidemics of BRD in Norway and that it often acts as the only viral agent. The phylogenetic analysis of the Norwegian strains of BRSV and several previously published isolates supported the theory of geographical and temporal clustering of BRSV.

  5. Analysis of the interaction between respiratory syncytial virus and lipid-rafts in Hep2 cells during infection

    International Nuclear Information System (INIS)

    Brown, Gaie; Jeffree, Chris E.; McDonald, Terence; McL Rixon, Helen W.; Aitken, James D.; Sugrue, Richard J.

    2004-01-01

    The assembly of respiratory syncytial virus (RSV) in lipid-rafts was examined in Hep2 cells. Confocal and electron microscopy showed that during RSV assembly, the cellular distribution of the complement regulatory proteins, decay accelerating factor (CD55) and CD59, changes and high levels of these cellular proteins are incorporated into mature virus filaments. The detergent-solubility properties of CD55, CD59, and the RSV fusion (F) protein were found to be consistent with each protein being located predominantly within lipid-raft structures. The levels of these proteins in cell-released virus were examined by immunoelectronmicroscopy and found to account for between 5% and 15% of the virus attachment (G) glycoprotein levels. Collectively, our findings suggest that an intimate association exists between RSV and lipid-raft membranes and that significant levels of these host-derived raft proteins, such as those regulating complement activation, are subsequently incorporated into the envelope of mature virus particles

  6. Detection of adenovirus and respiratory syncytial virus in patients with chronic obstructive pulmonary disease: Exacerbation versus stable condition.

    Science.gov (United States)

    Kokturk, Nurdan; Bozdayi, Gulendam; Yilmaz, Senay; Doğan, Bora; Gulbahar, Ozlem; Rota, Seyyal; Tatlicioglu, Turkan

    2015-08-01

    Latent infection with adenovirus and respiratory syncytial virus (RSV) is associated with chronic obstructive pulmonary disease (COPD). The role of respiratory viral infections are emerging in COPD exacerbations. The present study aimed to investigate the prevalence of adenovirus and RSV serotypes A and B in individuals with acute exacerbations of COPD (COPD-AE) and stable COPD. Twenty seven patients with COPD-AE were evaluated using a prospective longitudinal study design. Induced sputum, sera and nasal smears were sampled from patients experiencing COPD-AE and those in a stable condition. Adenoplex® multiplex polymerase chain reaction (PCR) kits and Invitek RTP® DNA/RNA Virus Mini kits were used for PCR assays of adenovirus and RSV, respectively. Eighteen patients who experienced a COPD-AE were also evaluated while in a stable condition. The results showed that three sputum samples were positive for adenovirus in patients experiencing an exacerbation, while one was positive among the patients in a stable condition. RSV serotype A was detected in 17/27 (63%) patients with COPD-AE and 10/18 (55.6%) patients in a stable condition. RSV serotype B was not detected. Patients with COPD-AE, who were positive for RSV serotype A exhibited higher serum fibrinogen levels than those who were negative (438.60 ± 126.08 mg/dl compared with 287.60 ± 85.91 mg/dl; P=0.004). Eight/ten patients who were positive for RSV serotype A while in a stable condition, were also positive during COPD-AE. The results of the present study suggested that RSV infection may be prevalent in patients with COPD-AE and in those in a stable condition. Therefore, chronic RSV infection may occur in COPD. The detection and prevention of RSV may be useful in the management of COPD.

  7. Immunobiotic Lactobacillus rhamnosus improves resistance of infant mice against respiratory syncytial virus infection.

    Science.gov (United States)

    Chiba, Eriko; Tomosada, Yohsuke; Vizoso-Pinto, Maria Guadalupe; Salva, Susana; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio

    2013-10-01

    Previously we showed that orally administered Lactobacillus rhamnosus CRL1505 beneficially regulated the balance between pro- and anti-inflammatory mediators in the lungs of poly(I:C)-challenged mice, allowing an effective inflammatory response against the TLR3/RIG-I agonist but at the same time reducing tissue damage. The aim of the present study was to investigate whether oral administration of the CRL1505 strain was able to improve resistance against respiratory syncytial virus (RSV) infection in infant mice and to evaluate the immunological mechanisms involved in the immunobiotic effect. We demonstrated that treatment of 3-week old BALB/c mice with L. rhamnosus CRL1505 significantly reduce lung viral loads and tissue injuries after the challenge with RSV. Moreover, we showed that the protective effect achieved by the CRL1505 strain is related to its capacity to differentially modulate respiratory antiviral immune response. Our results shows that IFN-γ and IL-10 secreted in response to L. rhamnosus CRL1505 oral stimulation would modulate the pulmonary innate immune microenvironment conducting to the activation of CD103(+) and CD11b(high) dendritic cells and the generation of CD3(+)CD4(+)IFN-γ(+) Th1 cells with the consequent attenuation of the strong and damaging Th2 reactions associated with RSV challenge. Our results indicate that modulation of the common mucosal immune system by immunobiotics could favor protective immunity against respiratory viral pathogens with a high attack rate in early infancy, such as RSV. © 2013.

  8. Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.

    Science.gov (United States)

    Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

    2018-01-05

    Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.

  9. Risk factors for respiratory syncytial virus hospitalisation in children with heart disease

    DEFF Research Database (Denmark)

    Kristensen, K; Stensballe, L G; Bjerre, J

    2009-01-01

    OBJECTIVE: To assess the risk and risk factors for respiratory syncytial virus (RSV) hospitalisation and determinants of the severity of RSV disease in children with heart disease. METHODS: By using a database on RSV tests in Denmark all children with RSV diagnosed with heart disease in Denmark...... from January 1996 to April 2003 were identified. For each case child one control child matched for age and centre was drawn from the population of children with heart disease. Clinical information was obtained through a review of all records. RESULTS: Data were obtained on 313 pairs. Median age...... at admission was 280 days (range 15-2379). In the multivariate analysis predictors of RSV hospitalisation were Down syndrome (odds ratio (OR) 3.24, 95% CI 1.80 to 5.80), cardiomyopathy (OR 5.84, 95% CI 1.26 to 27.16) and haemodynamically significant heart disease (OR 1.53, 95% CI 1.04 to 2.26). During RSV...

  10. Central nervous system alterations caused by infection with the human respiratory syncytial virus.

    Science.gov (United States)

    Bohmwald, Karen; Espinoza, Janyra A; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2014-11-01

    Worldwide, the human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization because of acute respiratory tract infections, including severe bronchiolitis and pneumonia. Despite intense research, to date there is neither vaccine nor treatment available to control hRSV disease burden globally. After infection, an incubation period of 3-5 days is usually followed by symptoms, such as cough and low-grade fever. However, hRSV infection can also produce a larger variety of symptoms, some of which relate to the individual's age at infection. Indeed, infants can display severe symptoms, such as dyspnea and chest wall retractions. Upon examination, crackles and wheezes are also common features that suggest infection by hRSV. Additionally, infection in infants younger than 1 year is associated with several non-specific symptoms, such as failure to thrive, periodic breathing or apnea, and feeding difficulties that usually require hospitalization. Recently, neurological symptoms have also been associated with hRSV respiratory infection and include seizures, central apnea, lethargy, feeding or swallowing difficulties, abnormalities in muscle tone, strabismus, abnormalities in the CSF, and encephalopathy. Here, we discuss recent findings linking the neurological, extrapulmonary effects of hRSV with infection and functional impairment of the CNS. Copyright © 2014 John Wiley & Sons, Ltd.

  11. A review of palivizumab and emerging therapies for respiratory syncytial virus.

    Science.gov (United States)

    Shadman, Kristin A; Wald, Ellen R

    2011-11-01

    Respiratory syncytial virus (RSV) is an important pathogen in children and adults; however, current treatment options are primarily supportive. Palivizumab, the only approved specific monoclonal antibody for RSV is used prophylactically to reduce morbidity in a select population of high-risk children. The development and current use of palivizumab; the potential role of palivizumab as preventive therapy in patients with cystic fibrosis, asthma and compromised immune systems; and explores the limited research in which palivizumab has been used for treatment of RSV. The modified recommendations for the use of palivizumab espoused by the American Academy of Pediatrics and research on the cost-effectiveness of this product are presented. In addition, the authors discuss the development of enhanced monoclonal antibodies including motavizumab, which was recently denied FDA approval for preventative therapy. The authors explore the historical and current efforts to develop a vaccine targeting RSV. The current status of antiviral drug development is also reviewed. The literature search included RSV-Ig, palivizumab, and emerging drugs and vaccines for the treatment of RSV as keywords and titles from 1997 to 2011. Although there are potential drugs and vaccines in development to prevent or reduce the effects of RSV infection, palivizumab remains the only licensed product to reduce the severity of disease in high-risk pediatric patients.

  12. Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Benedict, Sheela, E-mail: sheela.benedict@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Othman, Aws R., E-mail: aws.rashad@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Hartwig, Stacey M., E-mail: stacey-hartwig@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Varga, Steven M., E-mail: steven-varga@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Souid, Abdul-Kader, E-mail: asouid@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates)

    2014-04-15

    We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O{sub 2} consumption) and ATP following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection.

  13. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    International Nuclear Information System (INIS)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet; Quistgaard, Esben M.; Nordlund, Par; Thanabalu, Thirumaran; Torres, Jaume

    2015-01-01

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target

  14. ACUTE RESPIRATORY SYNCYTIAL VIRUS INFECTION IN CHILDREN IN THE AGE ASPECT

    Directory of Open Access Journals (Sweden)

    V. B. Rovny

    2013-01-01

    Full Text Available The clinical features of laboratory-confirmed acute respiratory syncytial virus infection (ARSVI are described in 221 children of the age from 1 month to 5 years. Febrile fever has been recorded in 76% of patients with ARSVI, and significantly more often in children in the second year of life (92%, but the difference in the temerature or duration has not been found. 98% of children have had symptoms of the lower respiratory tract lesions. The most common ARSVI manifestations in the patients of the first year of life were obstructive diseases of the lower respiratory tract (obstructive bronchitis in 53% and bronchiolitis in 11% of children, in the patients of the second year of life — pneumonia (28%, p < 0,05 and catarrhal otitis (26%; p < 0,05. Bronchial obstruction syndrome in children of the first year of life was characterized by the significantly higher frequency (73% and the maximal duration (9,7 ± 1,08 days. The largest number of cases of the severe respiratory failure has been recorded among patients of the second year of life (3 degree of respiratory failure in 22% of patients, p < 0,05.

  15. The respiratory syncytial virus nucleoprotein-RNA complex forms a left-handed helical nucleocapsid.

    Science.gov (United States)

    Bakker, Saskia E; Duquerroy, Stéphane; Galloux, Marie; Loney, Colin; Conner, Edward; Eléouët, Jean-François; Rey, Félix A; Bhella, David

    2013-08-01

    Respiratory syncytial virus (RSV) is an important human pathogen. Its nucleocapsid (NC), which comprises the negative sense RNA viral genome coated by the viral nucleoprotein N, is a critical assembly that serves as template for both mRNA synthesis and genome replication. We have previously described the X-ray structure of an NC-like structure: a decameric ring formed of N-RNA that mimics one turn of the helical NC. In the absence of experimental data we had hypothesized that the NC helix would be right-handed, as the N-N contacts in the ring appeared to more easily adapt to that conformation. We now unambiguously show that the RSV NC is a left-handed helix. We further show that the contacts in the ring can be distorted to maintain key N-N-protein interactions in a left-handed helix, and discuss the implications of the resulting atomic model of the helical NC for viral replication and transcription.

  16. Altered cardiac rhythm in infants with bronchiolitis and respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Galeone Carlotta

    2010-10-01

    Full Text Available Abstract Background Although the most frequent extra-pulmonary manifestations of respiratory syncytial virus (RSV infection involve the cardiovascular system, no data regarding heart function in infants with bronchiolitis associated with RSV infection have yet been systematically collected. The aim of this study was to verify the real frequency of heart involvement in patients with bronchiolitis associated with RSV infection, and whether infants with mild or moderate disease also risk heart malfunction. Methods A total of 69 otherwise healthy infants aged 1-12 months with bronchiolitis hospitalised in standard wards were enrolled. Pernasal flocked swabs were performed to collect specimens for the detection of RSV by real-time polymerase chain reaction, and a blood sample was drawn to assess troponin I concentrations. On the day of admission, all of the infants underwent 24-hour Holter ECG monitoring and a complete heart evaluation with echocardiography. Patients were re-evaluated by investigators blinded to the etiological and cardiac findings four weeks after enrolment. Results Regardless of their clinical presentation, sinoatrial blocks were identified in 26/34 RSV-positive patients (76.5% and 1/35 RSV-negative patients (2.9% (p Conclusions RSV seems associated with sinoatrial blocks and transient rhythm alterations even when the related respiratory problems are mild or moderate. Further studies are needed to clarify the mechanisms of these rhythm problems and whether they remain asymptomatic and transient even in presence of severe respiratory involvement or chronic underlying disease.

  17. [Incidence and severity of pertussis in infants with a respiratory syncytial virus infection].

    Science.gov (United States)

    Moreno Samos, María; Amores Torres, María; Pradillo Martín, María Cristina; Moreno-Pérez, David; Cordón Martínez, Ana; Urda Cardona, Antonio; Ramos Fernández, José Miguel

    2015-01-01

    Pertussis is a re-emerging disease that mostly affects infants. At this age, the severity can be affected by intercurrent infections such as respiratory syncytial virus (RSV). To estimate the incidence of RSV infection during an epidemic period in patients hospitalized due to pertussis. The impact on the severity was also observed during hospitalization. A descriptive study of cases diagnosed with pertussis admitted to a tertiary hospital over a 3year period, where the presence of co-infection with RSV was analyzed. The estimate of severity was estimated using the incidence of complications and the level of care required. From a total of 73 infants with pertussis, 34 occurred in a bronchiolitis season epidemic. A co-infection due to RSV was detected in 17 patients. The mean age was not significantly different compared to the non co-infected. The mean stay and the need for intensive care was similar in both groups. The need for oxygen therapy care and nutritional support was higher in the coinfected patients. Coinfection with RSV in infants hospitalized with pertussis occurred in ono in 2 patients during a RSV epidemic season, in infants of similar age. Severity in terms of stay, presence of apnea and admission to intensive care was similar, but more need for respiratory care and nutritional support was found. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Quistgaard, Esben M. [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Nordlund, Par [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Thanabalu, Thirumaran [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Torres, Jaume, E-mail: jtorres@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore)

    2015-08-15

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target.

  19. Respiratory syncytial virus is present in the neonatal intensive care unit.

    Science.gov (United States)

    Homaira, Nusrat; Sheils, Joanne; Stelzer-Braid, Sacha; Lui, Kei; Oie, Ju-Lee; Snelling, Tom; Jaffe, Adam; Rawlinson, William

    2016-02-01

    Nosocomial transmission of respiratory syncytial virus (RSV) occurs in children within the neonatal intensive care unit (NICU). During peak community RSV transmission, three swabs were collected from the nose, hand and personal clothing of visitors and health care workers (HCW) in NICU once every week for eight weeks. Nasal swabs were collected from every third neonate and from any neonate clinically suspected of having a respiratory infection. Environmental sampling of high touch areas was done once during the study period. All swabs were tested for RSV using real time RT-PCR. There were 173 (519 total) and 109 (327 total) swabs, each of nose, hand and dress from 84 HCWs and 80 visitors respectively and 81 nasal swabs from 55 neonates collected. Thirty five environmental swabs from surfaces of the beds, side tables, counter tops, chairs, tables and computers were collected. Overall 1% of nasal swabs from each of HCWs, visitors and neonates, 4% of dress specimens from visitors and 9% of environmental swabs were positive for RSV-RNA. The results suggest that though the risk for RSV in the NICU remains low, personnel clothing are contaminated with RSV-RNA and may have a role in transmission. © 2015 Wiley Periodicals, Inc.

  20. Retrospective Parameter Estimation and Forecast of Respiratory Syncytial Virus in the United States.

    Directory of Open Access Journals (Sweden)

    Julia Reis

    2016-10-01

    Full Text Available Recent studies have shown that systems combining mathematical modeling and Bayesian inference methods can be used to generate real-time forecasts of future infectious disease incidence. Here we develop such a system to study and forecast respiratory syncytial virus (RSV. RSV is the most common cause of acute lower respiratory infection and bronchiolitis. Advanced warning of the epidemic timing and volume of RSV patient surges has the potential to reduce well-documented delays of treatment in emergency departments. We use a susceptible-infectious-recovered (SIR model in conjunction with an ensemble adjustment Kalman filter (EAKF and ten years of regional U.S. specimen data provided by the Centers for Disease Control and Prevention. The data and EAKF are used to optimize the SIR model and i estimate critical epidemiological parameters over the course of each outbreak and ii generate retrospective forecasts. The basic reproductive number, R0, is estimated at 3.0 (standard deviation 0.6 across all seasons and locations. The peak magnitude of RSV outbreaks is forecast with nearly 70% accuracy (i.e. nearly 70% of forecasts within 25% of the actual peak, four weeks before the predicted peak. This work represents a first step in the development of a real-time RSV prediction system.

  1. Respiratory syncytial virus infection outbreak among pediatric patients with oncologic diseases and/or BMT.

    Science.gov (United States)

    Anak, Sema; Atay, Didem; Unuvar, Aysegul; Garipardic, Mesut; Agaoglu, Leyla; Ozturk, Gulyuz; Karakas, Zeynep; Devecioglu, Omer

    2010-03-01

    Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous/allogeneic hematopoetic stem cell transplantation (HSCT). There have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. Two RSV infection outbreaks developed between February-April 2006 and January-March 2009 in hospitalized pediatric patients for various hemato-oncological diseases + or - HSCT. A survey of respiratory viruses was done using direct immunofluorescent antibody assay from nasopharyngeal washing aspirate. In two RSV infection outbreaks (2006 and 2009), RSV antigen was detected in 6/30 patients. Five of six patients with RSV antigen were all treated with 0.2-0.4 g/kg intravenous immune globulin (IVIG) and specific antiviral therapy, oral ribavirin (20-25 mg/kg/day in three doses). Five patients recovered fully, although two were retreated due to recurrent (+) RSV antigen and respiratory symptoms within 2 weeks. We did not give oral ribavirin to one patient with (+) RSV antigen due to mild symptoms. All patients are alive and well. In contrast with the outcome of RSV infection in adult oncology patients, the mortality associated with RSV infection in pediatric oncology patients even in post bone marrow transplantation (BMT) period, is low when diagnosed and treated early enough. Oral ribavirin might be an option together with IVIG in the treatment of RSV especially when other forms of antivirals could not be obtained. This approach will make it possible to give the scheduled anti-neoplastic therapy on time.

  2. Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Xavier Roux

    Full Text Available BACKGROUND: Bronchiolitis caused by the respiratory syncytial virus (RSV in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N, has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS. METHODOLOGY AND PRINCIPAL FINDINGS: The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G. Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8(+ T cells and IFN-gamma-producing CD4(+ T cells. CONCLUSIONS/SIGNIFICANCE: This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.

  3. DNGR-1 is dispensable for CD8+ T-cell priming during respiratory syncytial virus infection.

    Science.gov (United States)

    Durant, Lydia R; Pereira, Catherine; Boakye, Aime; Makris, Spyridon; Kausar, Fahima; Goritzka, Michelle; Johansson, Cecilia

    2014-08-01

    During respiratory syncytial virus (RSV) infection CD8(+) T cells both assist in viral clearance and contribute to immunopathology. CD8(+) T cells recognize viral peptides presented by dendritic cells (DCs), which can directly present viral antigens when infected or, alternatively, "cross-present" antigens after endocytosis of dead or dying infected cells. Mouse CD8α(+) and CD103(+) DCs excel at cross-presentation, in part because they express the receptor DNGR-1 that detects dead cells by binding to exposed F-actin and routes internalized cell debris into the cross-presentation pathway. As RSV causes death in infected epithelial cells, we tested whether cross-presentation via DNGR-1 is necessary for CD8(+) T-cell responses to the virus. DNGR-1-deficient or wild-type mice were intranasally inoculated with RSV and the magnitude of RSV-specific CD8(+) T-cell induction was measured. We found that during live RSV infection, cross-presentation via DNGR-1 did not have a major role in the generation of RSV-specific CD8(+) T-cell responses. However, after intranasal immunization with dead cells infected with RSV, a dependence on DNGR-1 for RSV-specific CD8(+) T-cell responses was observed, confirming the ascribed role of the receptor. Thus, direct presentation by DCs may be the major pathway initiating CD8(+) T-cell responses to RSV, while DNGR-1-dependent cross-presentation has no detectable role. © 2014 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Molecular epidemiology and phylodynamics of the human respiratory syncytial virus fusion protein in northern Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsin Chi

    Full Text Available BACKGROUND AND AIMS: The glycoprotein (G protein and fusion protein (F protein of respiratory syncytial virus (RSV both show genetic variability, but few studies have examined the F protein gene. This study aimed to characterize the molecular epidemiology and phylodynamics of the F protein gene in clinical RSV strains isolated in northern Taiwan from 2000-2011. METHODS: RSV isolates from children presenting with acute respiratory symptoms between July 2000 and June 2011 were typed based on F protein gene sequences. Phylogeny construction and evaluation were performed using the neighbor-joining (NJ and maximum likelihood (ML methods. Phylodynamic patterns in RSV F protein genes were analyzed using the Bayesian Markov Chain Monte Carlo framework. Selection pressure on the F protein gene was detected using the Datamonkey website interface. RESULTS: From a total of 325 clinical RSV strains studied, phylogenetic analysis showed that 83 subgroup A strains (RSV-A could be further divided into three clusters, whereas 58 subgroup B strains (RSV-B had no significant clustering. Three amino acids were observed to differ between RSV-A and -B (positions 111, 113, and 114 in CTL HLA-B*57- and HLA-A*01-restricted epitopes. One positive selection site was observed in RSV-B, while none was observed in RSV-A. The evolution rate of the virus had very little change before 2000, then slowed down between 2000 and 2005, and evolved significantly faster after 2005. The dominant subtypes of RSV-A in each epidemic were replaced by different subtypes in the subsequent epidemic. CONCLUSIONS: Before 2004, RSV-A infections were involved in several small epidemics and only very limited numbers of strains evolved and re-emerged in subsequent years. After 2005, the circulating RSV-A strains were different from those of the previous years and continued evolving through 2010. Phylodynamic pattern showed the evolutionary divergence of RSV increased significantly in the recent 5

  5. Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms.

    Science.gov (United States)

    Douglas, Janet L; Panis, Marites L; Ho, Edmund; Lin, Kuei-Ying; Krawczyk, Steve H; Grant, Deborah M; Cai, Ruby; Swaminathan, Swami; Chen, Xiaowu; Cihlar, Tomas

    2005-06-01

    Here we present data on the mechanism of action of VP-14637 and JNJ-2408068 (formerly R-170591), two small-molecule inhibitors of respiratory syncytial virus (RSV). Both inhibitors exhibited potent antiviral activity with 50% effective concentrations (EC50s) of 1.4 and 2.1 nM, respectively. A similar inhibitory effect was observed in a RSV-mediated cell fusion assay (EC50=5.4 and 0.9 nM, respectively). Several drug-resistant RSV variants were selected in vitro in the presence of each compound. All selected viruses exhibited significant cross-resistance to both inhibitors and contained various single amino acid substitutions in two distinct regions of the viral F protein, the heptad repeat 2 (HR2; mutations D486N, E487D, and F488Y), and the intervening domain between HR1 and HR2 (mutation K399I and T400A). Studies using [3H]VP-14637 revealed a specific binding of the compound to RSV-infected cells that was efficiently inhibited by JNJ-2408068 (50% inhibitory concentration=2.9 nM) but not by the HR2-derived peptide T-118. Further analysis using a transient T7 vaccinia expression system indicated that RSV F protein is sufficient for this interaction. F proteins containing either the VP-14637 or JNJ-2408068 resistance mutations exhibited greatly reduced binding of [3H]VP-14637. Molecular modeling analysis suggests that both molecules may bind into a small hydrophobic cavity in the inner core of F protein, interacting simultaneously with both the HR1 and HR2 domains. Altogether, these data indicate that VP-14637 and JNJ-2408068 interfere with RSV fusion through a mechanism involving a similar interaction with the F protein.

  6. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model

    Science.gov (United States)

    Walsh, Paul; Behrens, Nicole; Carvallo Chaigneau, Francisco R.; McEligot, Heather; Agrawal, Karan; Newman, John W.; Anderson, Mark; Gershwin, Laurel J.

    2016-01-01

    Background Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2) which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase. Hypotheses We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected. Methods We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il)-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed. Results One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (pibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen. Conclusions Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes. However lung

  7. The eukaryotic elongation factor 1A is critical for genome replication of the paramyxovirus respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Ting Wei

    Full Text Available The eukaryotic translation factor eEF1A assists replication of many RNA viruses by various mechanisms. Here we show that down-regulation of eEF1A restricts the expression of viral genomic RNA and the release of infectious virus, demonstrating a biological requirement for eEF1A in the respiratory syncytial virus (RSV life cycle. The key proteins in the replicase/transcriptase complex of RSV; the nucleocapsid (N protein, phosphoprotein (P and matrix (M protein, all associate with eEF1A in RSV infected cells, although N is the strongest binding partner. Using individually expressed proteins, N, but not P or M bound to eEF1A. This study demonstrates a novel interaction between eEF1A and the RSV replication complex, through binding to N protein, to facilitate genomic RNA synthesis and virus production.

  8. The eukaryotic elongation factor 1A is critical for genome replication of the paramyxovirus respiratory syncytial virus.

    Science.gov (United States)

    Wei, Ting; Li, Dongsheng; Marcial, Daneth; Khan, Moshin; Lin, Min-Hsuan; Snape, Natale; Ghildyal, Reena; Harrich, David; Spann, Kirsten

    2014-01-01

    The eukaryotic translation factor eEF1A assists replication of many RNA viruses by various mechanisms. Here we show that down-regulation of eEF1A restricts the expression of viral genomic RNA and the release of infectious virus, demonstrating a biological requirement for eEF1A in the respiratory syncytial virus (RSV) life cycle. The key proteins in the replicase/transcriptase complex of RSV; the nucleocapsid (N) protein, phosphoprotein (P) and matrix (M) protein, all associate with eEF1A in RSV infected cells, although N is the strongest binding partner. Using individually expressed proteins, N, but not P or M bound to eEF1A. This study demonstrates a novel interaction between eEF1A and the RSV replication complex, through binding to N protein, to facilitate genomic RNA synthesis and virus production.

  9. Inferior immunogenicity and efficacy of respiratory syncytial virus fusion protein-based subunit vaccine candidates in aged versus young mice.

    Directory of Open Access Journals (Sweden)

    Corinne Cayatte

    Full Text Available Respiratory syncytial virus (RSV is recognized as an important cause of lower and upper respiratory tract infections in older adults, and a successful vaccine would substantially lower morbidity and mortality in this age group. Recently, two vaccine candidates based on soluble purified glycoprotein F (RSV F, either alone or adjuvanted with glucopyranosyl lipid A formulated in a stable emulsion (GLA-SE, failed to reach their primary endpoints in clinical efficacy studies, despite demonstrating the desired immunogenicity profile and efficacy in young rodent models. Here, one of the RSV F vaccine candidates (post-fusion conformation, RSV post-F, and a stabilized pre-fusion form of RSV F (RSV pre-F, DS-Cav1 were evaluated in aged BALB/c mice. Humoral and cellular immunogenicity elicited after immunization of naïve, aged mice was generally lower compared to young animals. In aged mice, RSV post-F vaccination without adjuvant poorly protected the respiratory tract from virus replication, and addition of GLA-SE only improved protection in the lungs, but not in nasal turbinates. RSV pre-F induced higher neutralizing antibody titers compared to RSV post-F (as previously reported but interestingly, RSV F-specific CD8 T cell responses were lower compared to RSV post-F responses regardless of age. The vaccines were also tested in RSV seropositive aged mice, in which both antigen forms similarly boosted neutralizing antibody titers, although GLA-SE addition boosted neutralizing activity only in RSV pre-F immunized animals. Cell-mediated immune responses in the aged mice were only slightly boosted and well below levels induced in seronegative young mice. Taken together, the findings suggest that the vaccine candidates were not able to induce a strong anti-RSV immune response in recipient mice with an aged immune system, in agreement with recent human clinical trial results. Therefore, the aged mouse model could be a useful tool to evaluate improved vaccine

  10. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013.

    Directory of Open Access Journals (Sweden)

    Rungnapa Malasao

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR. Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%, of which 305 (72.1% and 118 (27.9% were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05 and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines.

  11. The Economics of Strategies to Reduce Respiratory Syncytial Virus Hospitalizations in Alaska.

    Science.gov (United States)

    Borse, Rebekah H; Singleton, Rosalyn J; Bruden, Dana T; Fry, Alicia M; Hennessy, Thomas W; Meltzer, Martin I

    2014-09-01

    Alaska Native infants experience high rates of respiratory syncytial virus (RSV) hospitalizations. Through 2008, Alaska administered a 7-dose (maximum) palivizumab regime to high-risk infants from October to May. In 2009, the maximum was reduced to 3 doses for 32- to 34-week preterm babies and 6 doses for other groups. We used 11 years of data and regional Medicaid reimbursement rates to model the cost effectiveness of 4 palivizumab intervention strategies to reduce RSV hospitalizations among Alaskan infants including: current strategy, old strategy (1998-2008), and 2 hypothetical strategies using the current strategy plus 1 or 3 doses to all newborn infants during the RSV season. The current strategy represents 5 hospitalizations averted per year for the palivizumab cohort (∼50-56 children) at ∼$52 846 per hospitalization averted, compared with no intervention. Compared with the old strategy, the mean cost per hospitalization prevented for the current strategy was 63% lower, net program costs were 85% lower, and the mean hospitalizations prevented were 27% lower. Compared with current strategy only, the addition of 1 dose to all newborns during the RSV season could decrease the mean cost per hospitalization prevented by 23%, increase the number of hospitalizations prevented by 2.5-fold, and increase the net programmatic costs by 3.3-fold; administering up to 3 doses to infants further reduced hospitalizations and increased costs. The current palivizumab strategy improved the cost-effectiveness ratio compared with the old strategy. Further improvement could be obtained by adding doses for Alaskan Native newborns during the RSV season; however, programmatic costs would increase. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. [Effect of interferon-γ on airway inflammation following respiratory syncytial virus reinfection in mice].

    Science.gov (United States)

    Long, X R; Xie, J; Li, W; Zhao, K T; Xie, X H; Wang, L J; Ren, L; Liu, E M; Deng, Y

    2017-10-02

    Objective: To identify the role of interferon (IFN)-γ during respiratory syncytial virus (RSV) re-infection in mice. Method: Female wild type C57BL/6 mice and IFN-γ knockout mice (IFN-γ(-/-) mice) at the age of 6 to 8 weeks were randomly divided into two groups: control group and RSV group, according to random number table.Each group was further divided into primary infection group and re-infection group.There were 8 groups.Mice were sacrificed on days 5, 7, 14 to collect samples.There were 5-8 mice in each group at each time point.And experiment was repeated twice. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, left lung tissues were stained with HE and histopathological scoring (HPS) was performed.The concentrations of IFN-γ, IL-5, IL-13 were determined with ELISA. T test or single factor analysis of variance was used to compare between groups. Result: (1) Mice infected or reinfected with RSV showed pale hair, weight loss, decreased activity and anorexia.(2) IFN-γ levels significantly increased on days 5 and 7 following RSV primary infection and reinfection as compared to control groups in wild type mice ((192±44) vs .(36±8) and (531±161) vs .(23±4) pg/ml on day 5, (100±23) vs .(36±8) and (862±186) vs .(23±4) pg/ml on day 7, t =2.654, 2.513, 2.654, 3.968, all P mice, RSV-reinfected wild type mice had less body weight loss ((13.6±2.6)% vs .(22.7±2.9)% on day 5, (18.0±3.1)% vs .(26.5±1.8)% on day 7, t =2.314, 2.308, both P mice.

  13. Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma

    Directory of Open Access Journals (Sweden)

    Heinzmann Andrea

    2007-05-01

    Full Text Available Abstract Background Surfactant proteins (SP are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma. Methods We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses. Results The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034. Conclusion Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.

  14. [Respiratory syncytial virus outbreak in a tertiary hospital Neonatal Intensive Care Unit].

    Science.gov (United States)

    Moreno Parejo, Carlos; Morillo García, Aurea; Lozano Domínguez, Carmen; Carreño Ochoa, Concepción; Aznar Martín, Javier; Conde Herrera, Manuel

    2016-09-01

    Investigation and control of a respiratory syncytial virus (RSV) outbreak that affected the Neonatal Intensive Care Unit (NICU) of a university hospital from October to December 2012. Cohort study of children admitted to the NICU. The infection attack rate was calculated. A descriptive analysis of the cases and a multivariate analysis was performed using the variables that were shown to be risk factors for RSV infection. Preventive measures taken were: contact isolation; hand hygiene training and observation; exclusivity of a health team of nurses and physicians for positive cases, restrictions on visitor numbers; surveillance RSV testing, and palivizumab prophylaxis. The outbreak had three epidemic waves and 20 positive cases out of a total of 48 children admitted. The overall attack rate was 42%. Half of positive cases were children, with a median age of 36 days (p25=22, p75=58). The independent risk factors for RSV infection were birth weight below 1000 grams (OR=23.5; P=.002) and to have another nosocomial infection the week before the diagnosis of RSV infection (OR=19.98; P=.016). It was an outbreak with a high number of cases, due to the delay in notification, prolonged RSV carrier status, and low adherence to hand hygiene practice, which favoured the cross-transmission of infection. The most effective preventive measures were direct observation of hand hygiene and supervision of isolation measures. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013.

    Science.gov (United States)

    Malasao, Rungnapa; Okamoto, Michiko; Chaimongkol, Natthawan; Imamura, Tadatsugu; Tohma, Kentaro; Dapat, Isolde; Dapat, Clyde; Suzuki, Akira; Saito, Mayuko; Saito, Mariko; Tamaki, Raita; Pedrera-Rico, Gay Anne Granada; Aniceto, Rapunzel; Quicho, Reynaldo Frederick Negosa; Segubre-Mercado, Edelwisa; Lupisan, Socorro; Oshitani, Hitoshi

    2015-01-01

    Human respiratory syncytial virus (HRSV) is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR). Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR) of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%), of which 305 (72.1%) and 118 (27.9%) were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (pPhilippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines.

  16. Prospective Evaluation of Rapid Antigen Tests for Diagnosis of Respiratory Syncytial Virus and Human Metapneumovirus Infections▿

    Science.gov (United States)

    Aslanzadeh, Jaber; Zheng, Xiaotian; Li, Haijing; Tetreault, Janice; Ratkiewicz, Irene; Meng, Shufang; Hamilton, Pamela; Tang, Yi-Wei

    2008-01-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two important viral pathogens that cause respiratory tract infections in the pediatric population. The rapid detection of these agents allows the prompt isolation and treatment of infected patients. In the present prospective study, we evaluated the performances of four rapid antigen detection assays, including a rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke, Hampshire, United Kingdom). The clinical specimens tested comprised 515 nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at Hartford Hospital from 1 November 2006 to 21 April 2007. Compared to the results of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of 79.8% and a specificity of 89.5%. The RSV DFA with Bartels reagents showed a sensitivity of 94.1% and a specificity of 96.8%. For hMPV, the sensitivity and specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and 100%, respectively, for the Imagen DFA. The hands-on and test turnaround times for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively. We conclude that while the RSV CIA is user-friendly, it lacks sensitivity and specificity, especially during off-peak months. In contrast, the RSV DFA is more sensitive and specific, but interpretation of its results is subjective and it demands technical time and expertise. Similarly, both hMPV DFAs are highly specific in comparison to the results of RT-PCR, but their sensitivities await further improvements. PMID:18337386

  17. Prospective evaluation of rapid antigen tests for diagnosis of respiratory syncytial virus and human metapneumovirus infections.

    Science.gov (United States)

    Aslanzadeh, Jaber; Zheng, Xiaotian; Li, Haijing; Tetreault, Janice; Ratkiewicz, Irene; Meng, Shufang; Hamilton, Pamela; Tang, Yi-Wei

    2008-05-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two important viral pathogens that cause respiratory tract infections in the pediatric population. The rapid detection of these agents allows the prompt isolation and treatment of infected patients. In the present prospective study, we evaluated the performances of four rapid antigen detection assays, including a rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke, Hampshire, United Kingdom). The clinical specimens tested comprised 515 nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at Hartford Hospital from 1 November 2006 to 21 April 2007. Compared to the results of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of 79.8% and a specificity of 89.5%. The RSV DFA with Bartels reagents showed a sensitivity of 94.1% and a specificity of 96.8%. For hMPV, the sensitivity and specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and 100%, respectively, for the Imagen DFA. The hands-on and test turnaround times for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively. We conclude that while the RSV CIA is user-friendly, it lacks sensitivity and specificity, especially during off-peak months. In contrast, the RSV DFA is more sensitive and specific, but interpretation of its results is subjective and it demands technical time and expertise. Similarly, both hMPV DFAs are highly specific in comparison to the results of RT-PCR, but their sensitivities await further improvements.

  18. Clinical characterization of influenza A and human respiratory syncytial virus among patients with influenza like illness.

    Science.gov (United States)

    Saxena, Swati; Singh, Dharamveer; Zia, Amreen; Umrao, Jyoti; Srivastava, Naveen; Pandey, Ankita; Singh, Sushma; Bhattacharya, Piyali; Kumari, Reema; Kushwaha, Ramawadh; Dhole, T N

    2017-01-01

    Influenza A and Respiratory Syncytial Virus (RSV) has been recognized as a major cause of acute respiratory tract infection. H1N1 is one of the subtypes of influenza A, pandemic worldwide in July 2009, causing 18,449 deaths globally. To investigate the prevalence and clinical manifestation of the influenza A, H1N1pdm09, and RSV. Throat/nasal swab collected from the patients of all age group either outpatients/inpatients having respiratory illness from 2 to 5 days. The clinical data were recorded in a predesigned questionnaire. RNA was extracted and analyzed by real time PCR at a tertiary care center, 2009-2014. Total 4,352 samples tested for influenza A and H1N1. Out of 4,352, 32.2% (median positivity 21%; range 16-41% during 6 years) were positive for influenza A and 19% were H1N1 (median positivity 16.7%; range 8.7-23% during 6 years). Total 1653 samples were analyzed for RSV from 2011 to 2014, 12% were RSV positive (median positivity 11.35%; range 10-16.3% during 4 years). Pharyngitis, dyspnea were frequent symptoms in influenza A and H1N1 (P influenza A and H1N1 was higher in age-group 21-30, whereas RSV in infant and children. H1N1 and RSV were co-circulated and have common clinical symptoms particularly in lower age group. Therefore, laboratory confirmation is necessary for further disease prognosis. Age was an important risk factor that affects the positivity of influenza A, H1N1, and RSV. Different clinical manifestation of H1N1 and RSV will be helpful for early and accurate diagnosis. J. Med. Virol. 89:49-54, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Caesarean section and hospitalization for respiratory syncytial virus infection: a population-based study.

    Science.gov (United States)

    Kristensen, Kim; Fisker, Niels; Haerskjold, Ann; Ravn, Henrik; Simões, Eric A F; Stensballe, Lone

    2015-02-01

    Hospitalization for respiratory syncytial virus (RSV) infection and asthma share common determinants, and meta-analyses indicate that children delivered by caesarean section (CS) are at increased risk of asthma. We aimed to investigate whether birth by CS is associated with an increased risk of hospitalization for RSV illness. This was a population-based national register-based cohort study, conducted between January, 1997 and June, 2003, which included all children born in Denmark and all hospitalizations for RSV disease in them from 0 to 23 months of age. We used Cox regression with adjustment for prematurity, asphyxia, birthweight, multiple births, single parenthood, maternal smoking during pregnancy, older siblings and asthma diagnoses up to 2 weeks before hospitalization for RSV infection, to compare the effects of acute or elective CS versus vaginal delivery, on subsequent hospitalization for RSV disease. A test for homogeneity was used to assess for effect over time. 399,175 children with 10,758 hospitalizations for RSV illness were included; 31,715 were born by acute CS and 30,965 by elective CS. Adjusted hazard ratios for hospitalization for RSV infection in children born by acute CS and by elective CS were 1.09 (1.01-1.17) and 1.27 (1.19-1.36), respectively. The effect of elective CS remained unchanged throughout the first 2 years of life (P = 0.53), whereas the effect of acute CS was only present in the second year of life (P = 0.001). Delivery by caesarian section is associated with an increased risk of hospitalization for RSV infection. This effect continues at least throughout the first 2 years of life.

  20. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Arim; Suh, Sang-il; Seol, Hae-Young [Korea University College of Medicine, Department of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of); Son, Gyu-Ri; Lee, Nam-Joon [Korea University College of Medicine, Department of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Lee, Young Hen; Seo, Hyung Suk [Korea University College of Medicine, Department of Radiology, Korea University Ansan Hospital, Gyeonggi-do (Korea, Republic of); Eun, Baik-Lin [Korea University College of Medicine, Department of Pediatrics, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2014-02-15

    Respiratory syncytial virus (RSV) is a common pathogen causing acute respiratory infection in children. Herein, we describe the incidence and clinical and magnetic resonance imaging (MRI) findings of RSV-related encephalitis, a major neurological complication of RSV infection. We retrospectively reviewed the medical records and imaging findings of the patients over the past 7 years who are admitted to our medical center and are tested positive for RSV-RNA by reverse transcriptase PCR. In total, 3,856 patients were diagnosed with RSV bronchiolitis, and 28 of them underwent brain MRI for the evaluation of neurologic symptoms; 8 of these 28 patients had positive imaging findings. Five of these 8 patients were excluded because of non-RSV-related pathologies, such as subdural hemorrhage, brain volume loss due to status epilepticus, periventricular leukomalacia, preexisting ventriculomegaly, and hypoxic brain injury. The incidence of RSV-related encephalitis was as follows: 3/3,856 (0.08 %) of the patients are positive for RSV RNA, 3/28 (10.7 %) of the patient underwent brain MRI for neurological symptom, and 3/8 (37.5 %) of patients revealed abnormal MR findings. The imaging findings were suggestive of patterns of rhombenmesencephalitis, encephalitis with acute disseminated encephalomyelitis, and limbic encephalitis. They demonstrated no diffusion abnormality on diffusion-weighted image and symptom improvement on the follow-up study. Encephalitis with RSV bronchiolitis occurs rarely. However, on brain MRI performed upon suspicion of neurologic involvement, RSV encephalitis is not infrequently observed among the abnormal MR findings and may mimic other viral and limbic encephalitis. Physicians should be aware of this entity to ensure proper diagnosis and neurologic care of RSV-positive patients. (orig.)

  1. Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

    Science.gov (United States)

    Yoshida, Shuichiro; Noguchi, Atsuko; Kikuchi, Wataru; Fukaya, Hiroshi; Igarashi, Kiyoshi; Takahashi, Tsutomu

    2017-12-01

    Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

  2. Evaluation of an alternative chest physiotherapy method in infants with respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Postiaux, Guy; Louis, Jacques; Labasse, Henri C; Gerroldt, Julien; Kotik, Anne-Claire; Lemuhot, Amandine; Patte, Caroline

    2011-07-01

    We proposed a new chest physiotherapy (CPT) secretion clearance method to treat respiratory syncytial virus bronchiolitis in infants. Our new CPT method consists of 15 prolonged slow expirations, then 5 provoked cough maneuvers. We randomized 20 infants (mean age 4.2 months) into 2 groups: 8 patients received 27 sessions of nebulization of hypertonic saline; 12 patients received 31 sessions of nebulization of hypertonic saline followed by our new CPT method. We used the Wang clinical severity scoring system (which assesses wheezing, respiratory rate, retractions, and general condition) and measured S(pO(2)) and heart rate before each CPT session (T0), immediately after the 30-min session (T30), and 120 min after the session (T150). Within the groups: in the first group, Wang score was significantly lower at T150 than at T0: 4.6 vs 5.0 (P = .008). In the new-method-CPT group, Wang score was significantly lower at T30 (3.6 vs 4.3, P = .001) and at T150 (3.7 vs 4.3, P = .002). Wheezing score was significantly lower at T150 than at T0 (1.1 vs 1.2, P = .02) in the first group, and in the new-method-CPT group at T30 than at T0 (0.8 vs 1.3, P = .001) and at T150 than at T0 (0.9 vs 1.3, P = .001). Between the groups: at T30 the improvement was significantly better in the new-method-CPT group for overall Wang score (P = .02), retractions (P = .05), respiratory rate (P = .001), and heart rate (P bronchiolitis.

  3. Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Mallika Sastry

    Full Text Available Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C and Poly (IC:LC, respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50 were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS, an oil-in-water adjuvant, plus Carbopol; high responses (3658-7108 were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C and Poly (IC:LC; and moderate responses (1251-2129 were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6. A balanced IgG1 and IgG2a (Th2/Th1 immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex. We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the

  4. Effects of formalin-inactivated respiratory syncytial virus (FI-RSV in the perinatal lamb model of RSV.

    Directory of Open Access Journals (Sweden)

    Rachel J Derscheid

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV conducted in the 1960's that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3-5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.

  5. Monoclonal Antibody against G Glycoprotein Increases Respiratory Syncytial Virus Clearance In Vivo and Prevents Vaccine-Enhanced Diseases.

    Directory of Open Access Journals (Sweden)

    Hyo-Jeong Lee

    Full Text Available Respiratory syncytial virus (RSV is a common cause of lower respiratory tract illness in infants, young children, and the elderly. The G glycoprotein plays a role in host cell attachment and also modulates the host immune response, thereby inducing disease pathogenesis. We generated two monoclonal antibodies (mAbs; 5H6 and 3A5 against G protein core fragment (Gcf, which consisted of amino acid residues 131 to 230 from RSV A2 G protein. Epitope mapping study revealed that 5H6 specifically binds to the G/164-176 peptide that includes conserved sequences shared by both RSV A and B subtypes, and 3A5 binds to the G/190-204 peptide. Studies with mutant Gcf proteins in which cysteine residues were substituted with alanine revealed that 5H6 requires four cysteines for binding and 3A5 binds to Gcf variants with alanine substitutions better than wild-type. To determine if these mAbs reduce pulmonary viral infection, BALB/c mice were administered mAb and subsequently challenged with RSV. On day 4 post-infection, lung viral titers were reduced by up to 93% with the 5H6 injection and 90% with the 3A5 injection, indicating that prophylactic injection of these mAbs contributes to RSV clearance in vivo. Importantly, 5H6 injection reduced vaccine-enhanced diseases. Overall, our results suggest that this novel anti-G mAb could be used as a prophylactic regimen against RSV diseases.

  6. Immunogenicity of a modified-live virus vaccine against bovine viral diarrhea virus types 1 and 2, infectious bovine rhinotracheitis virus, bovine parainfluenza-3 virus, and bovine respiratory syncytial virus when administered intranasally in young calves.

    Science.gov (United States)

    Xue, Wenzhi; Ellis, John; Mattick, Debra; Smith, Linda; Brady, Ryan; Trigo, Emilio

    2010-05-14

    The immunogenicity of an intranasally-administered modified-live virus (MLV) vaccine in 3-8 day old calves was evaluated against bovine viral diarrhea virus (BVDV) types 1 and 2, infectious bovine rhinotracheitis (IBR) virus, parainfluenza-3 (PI-3) virus and bovine respiratory syncytial virus (BRSV). Calves were intranasally vaccinated with a single dose of a multivalent MLV vaccine and were challenged with one of the respective viruses three to four weeks post-vaccination in five separate studies. There was significant sparing of diseases in calves intranasally vaccinated with the MLV vaccine, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding, greater white blood cell and platelet counts, and less severe pulmonary lesions than control animals. This was the first MLV combination vaccine to demonstrate efficacy against BVDV types 1 and 2, IBR, PI-3 and BRSV in calves 3-8 days of age. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Proteome analysis of bronchoalveolar lavage from calves infected with bovine respiratory syncytial virus-Insights in pathogenesis and perspectives for new treatments.

    Directory of Open Access Journals (Sweden)

    Sara Hägglund

    Full Text Available Human and bovine respiratory syncytial viruses (HRSV/BRSV are major causes of severe lower respiratory tract infections in children and calves, respectively. Shared epidemiological, clinical, pathological and genetic characteristics of these viruses make comparative research highly relevant. To characterise the host response against BRSV infection, bronchoalveolar lavage supernatant (BAL from i non-vaccinated, BRSV-infected ii vaccinated, BRSV-infected and iii non-infected calves was analysed by tandem mass spectrometry. Proteins were semi-quantified and protein expression was validated by immunoblotting. Correlations between selected proteins and pathology, clinical signs and virus shedding were investigated. Calves with BRSV-induced disease had increased total protein concentrations and a decreased number of proteins identified in BAL. The protein profile was characterised by neutrophil activation and a reduction in identified antioxidant enzymes. The presence of neutrophils in alveolar septa, the expression level of neutrophil-related or antioxidant proteins and LZTFL1 correlated significantly with disease. Citrullinated histone 3, an indicator of extracellular traps (ETs, was only detected in non-vaccinated, BRSV-infected animals. By bringing disequilibrium in the release and detoxification of reactive oxygen species, generating ETs and causing elastine degradation, exaggerated neutrophil responses might exacerbate RSV-induced disease. Neutrophil-mitigating or antioxidant treatments should be further explored.

  8. Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Hiroaki Nakamura

    2018-04-01

    Full Text Available Background: Periostin and squamous cell carcinoma antigen (SCCA are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. Methods: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI had been met: Group I consisted of mAPI (+ and mAPI (− patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339. Results: We enrolled 14 subjects in Group I mAPI (+, 22 in Group I mAPI (−, 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+ and mAPI (−. Conclusions: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV. Keywords: Infants, Periostin, Respiratory syncytial virus, Squamous cell carcinoma antigen, T-helper 2 cell cytokines

  9. Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus.

    Science.gov (United States)

    Vanheule, Vincent; Vervaeke, Peter; Mortier, Anneleen; Noppen, Sam; Gouwy, Mieke; Snoeck, Robert; Andrei, Graciela; Van Damme, Jo; Liekens, Sandra; Proost, Paul

    2016-01-15

    Chemokines attract leukocytes to sites of infection in a G protein-coupled receptor (GPCR) and glycosaminoglycan (GAG) dependent manner. Therefore, chemokines are crucial molecules for proper functioning of our antimicrobial defense mechanisms. In addition, some chemokines have GPCR-independent defensin-like antimicrobial activities against bacteria and fungi. Recently, high affinity for GAGs has been reported for the positively charged COOH-terminal region of the chemokine CXCL9. In addition to CXCL9, also CXCL12γ has such a positively charged COOH-terminal region with about 50% positively charged amino acids. In this report, we compared the affinity of COOH-terminal peptides of CXCL9 and CXCL12γ for GAGs and KD values in the low nM range were detected. Several enveloped viruses such as herpesviruses, hepatitis viruses, human immunodeficiency virus (HIV), dengue virus (DENV), etc. are known to bind to GAGs such as the negatively charged heparan sulfate (HS). In this way GAGs are important for the initial contacts between viruses and host cells and for the infection of the cell. Thus, inhibiting the virus-cell interactions, by blocking GAG-binding sites on the host cell, might be a way to target multiple virus families and resistant strains. This article reports that the COOH-terminal peptides of CXCL9 and CXCL12γ have antiviral activity against DENV serotype 2, clinical and laboratory strains of herpes simplex virus (HSV)-1 and respiratory syncytial virus (RSV). Moreover, we show that CXCL9(74-103) competes with DENV envelope protein domain III for binding to heparin. These short chemokine-derived peptides may be lead molecules for the development of novel antiviral agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of respiratory syncytial virus in different settings in a developing country

    DEFF Research Database (Denmark)

    Stensballe, L G; Trautner, S; Kofoed, P-E

    2002-01-01

    OBJECTIVE: To compare detection of respiratory syncytial virus (RSV) for diagnostic purposes using nasopharyngeal aspirate (NPA) and nasal swabs (NS) in different clinical settings in a community study in Guinea-Bissau. METHOD: During 1996-98 paired specimens were obtained from 635 children under...

  11. Clinical relevance of prevention of respiratory syncytial virus lower respiratory tract infection in preterm infants born between 33 and 35 weeks gestational age

    NARCIS (Netherlands)

    Carbonell-Estrany, X.; Bont, L.; Doering, G.; Gouyon, J-B; Lanari, M.

    2008-01-01

    Premature infants are vulnerable to severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) resulting in hospitalisation and the potential for longer-term respiratory morbidity. Whilst the severity and consequence of RSV LRTI are generally accepted and recognised in infants

  12. Confirmation of an Association Between Single Nucleotide Polymorphisms in the VDR Gene With Respiratory Syncytial Virus Related Disease in South African Children

    NARCIS (Netherlands)

    Kresfelder, T. L.; Janssen, R.; Bont, L.; Venter, M.

    2011-01-01

    Respiratory syncytial virus is a leading cause of lower respiratory tract infection in infants. Disease severity has been linked to host immune responses and polymorphisms in genes associated with innate immunity. A large-scale genetics study of single nucleotide polymorphisms (SNPs) in children in

  13. Infection-enhancing lipopeptides do not improve intranasal immunization of cotton rats with a delta-G candidate live-attenuated human respiratory syncytial virus vaccine

    NARCIS (Netherlands)

    D.T. Nguyen (Tien); J. Boes (Jolande); G. van Amerongen (Geert); Y. van Remmerden (Yvonne); S. Yüksel (Selma); T. Guichelaar (Teun); A.D.M.E. Osterhaus (Albert); R.L. de Swart (Rik)

    2013-01-01

    textabstractDevelopment of live-attenuated human respiratory syncytial virus (HRSV) vaccines has proven to be difficult. Several vaccine candidates were found to be over-attenuated and displayed limited immunogenicity. Recently, we identified three synthetic cationic lipopeptides that enhanced

  14. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Salomonsen, Charlotte Mark; Breum, Solvej Østergaard; Larsen, Lars Erik

    2012-01-01

    Background Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with...

  15. Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection

    NARCIS (Netherlands)

    Do, Lien Anh Ha; Pellet, Johann; van Doorn, H. Rogier; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Nguyen, Huu Mai Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; de Meulder, Bertrand; Auffray, Charles; Hofstra, Jorrit-Jan; Farrar, Jeremy; Bryant, Juliet E.; de Jong, Menno; Hibberd, Martin L.

    2017-01-01

    Most insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. In this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV

  16. Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity

    NARCIS (Netherlands)

    Do, Lien Anh Ha; Bryant, Juliet E.; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; van Doorn, H. Rogier

    2016-01-01

    Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical

  17. Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from Vietnamese children identifies distinct patterns of inter- and intra-host evolution

    NARCIS (Netherlands)

    Do, Lien Anh Ha; Wilm, Andreas; van Doorn, H. Rogier; Lam, Ha Minh; Sim, Shuzhen; Sukumaran, Rashmi; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; Chen, Swaine; Nagarajan, Niranjan; Bryant, Juliet E.; Hibberd, Martin Lloyd

    2015-01-01

    Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children under two years of age. Little is known about RSV intra-host genetic diversity over the course of infection, or about the immune pressures that drive RSV molecular evolution. We performed

  18. Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease : A randomized equivalence trial

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; van Woensel, Job B. M.; Uijtendaal, Esther; Uiterwaal, Cuno S. P. M.; Kimpen, Jan L. L.

    Background: Nearly halt of all hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) are treated with (parenteral) antibiotics. The present study was designed to test our hypothesis that the use of antibiotics would not lead to a reduced duration of

  19. Lack of long-term effects of high-dose inhaled beclomethasone for respiratory syncytial virus bronchiolitis: a randomized placebo-controlled trial

    NARCIS (Netherlands)

    Zomer-Kooijker, K.; Ent, C.K. van der; Ermers, M.J.; Rovers, M.M.; Bont, L.J.; et al.,

    2014-01-01

    BACKGROUND: Previously, we showed that high-dose early initiated inhaled corticosteroids during respiratory syncytial virus bronchiolitis partially and transiently prevents subsequent recurrent wheeze. Here, we study treatment effect on lung function at age 6. METHODS: This is a 6-year follow-up

  20. A virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A provides protection against viral challenge without priming for enhanced disease in cotton rats

    NARCIS (Netherlands)

    Kamphuis, Tobias; Stegmann, Toon; Meijerhof, Tjarko; Wilschut, Jan; de Haan, Aalzen

    2013-01-01

    Background Non-replicating respiratory syncytial virus (RSV) vaccine candidates could potentially prime for enhanced respiratory disease (ERD) due to a T-cell-mediated immunopathology, following RSV infection. Vaccines with built-in immune response modifiers, such as Toll-like receptor (TLR)

  1. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015 : A systematic review and modelling study

    NARCIS (Netherlands)

    Shi, Ting; McAllister, David A.; O'Brien, Katherine L.; Simoes, Eric A. F.; Madhi, Shabir A.; Gessner, Bradford D.; Polack, Fernando P.; Balsells, Evelyn; Acacio, Sozinho; Aguayo, Claudia; Alassani, Issifou; Ali, Asad; Antonio, Martin; Awasthi, Shally; Awori, Juliet O.; Azziz-Baumgartner, Eduardo; Baggett, Henry C.; Baillie, Vicky L.; Balmaseda, Angel; Barahona, Alfredo; Basnet, Sudha; Bassat, Quique; Basualdo, Wilma; Bigogo, Godfrey; Bont, Louis; Breiman, Robert F.; Brooks, W. Abdullah; Broor, Shobha; Bruce, Nigel; Bruden, Dana; Buchy, Philippe; Campbell, Stuart; Carosone-Link, Phyllis; Chadha, Mandeep; Chipeta, James; Chou, Monidarin; Clara, Wilfrido; Cohen, Cheryl; de Cuellar, Elizabeth; Dang, Duc Anh; Dash-yandag, Budragchaagiin; Deloria-Knoll, Maria; Dherani, Mukesh; Eap, Tekchheng; Ebruke, Bernard E.; Echavarria, Marcela; de Freitas Lázaro Emediato, Carla Cecília; Fasce, Rodrigo A.; Feikin, Daniel R.; Feng, Luzhao; Gentile, Angela; Gordon, Aubree; Goswami, Doli; Goyet, Sophie; Groome, Michelle J; Halasa, Natasha; Hirve, Siddhivinayak; Homaira, Nusrat; Howie, Stephen R.C.; Jara, Jorge; Jroundi, Imane; Kartasasmita, Cissy B.; Khuri-Bulos, Najwa; Kotloff, Karen L.; Krishnan, Anand; Libster, Romina; Lopez, Olga; Lucero, Marilla G.; Lucion, Florencia; Lupisan, Socorro P.; Marcone, Debora N.; McCracken, John P.; Mejia, Mario; Moisi, Jennifer C.; Montgomery, Joel M.; Moore, David P.; Moraleda, Cinta; Moyes, Jocelyn; Munywoki, Patrick; Mutyara, Kuswandewi; Nicol, Mark P.; Nokes, D. James; Nymadawa, Pagbajabyn; da Costa Oliveira, Maria Tereza; Oshitani, Histoshi; Pandey, Nitin; Paranhos-Baccalà, Gláucia; Phillips, Lia N.; Picot, Valentina Sanchez; Rahman, Mustafizur; Rakoto-Andrianarivelo, Mala; Rasmussen, Zeba A.; Rath, Barbara A.; Robinson, Annick; Romero, Candice; Russomando, Graciela; Salimi, Vahid; Sawatwong, Pongpun; Scheltema, Nienke; Schweiger, Brunhilde; Scott, J. Anthony G.; Seidenberg, Phil; Shen, Kunling; Singleton, Rosalyn; Sotomayor, Viviana; Strand, Tor A.; Sutanto, Agustinus; Sylla, Mariam; Tapia, Milagritos D.; Thamthitiwat, Somsak; Thomas, Elizabeth D.; Tokarz, Rafal; Turner, Claudia; Venter, Marietjie; Waicharoen, Sunthareeya; Wang, Jianwei; Watthanaworawit, Wanitda; Yoshida, Lay Myint; Yu, Hongjie; Zar, Heather J.; Campbell, Harry; Nair, Harish

    2017-01-01

    Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on

  2. Evaluation of a multiplex immunoassay for bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk against two indirect ELISAs using latent class analysis

    DEFF Research Database (Denmark)

    Toftaker, Ingrid; Toft, Nils; Stokstad, Maria

    2018-01-01

    Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV) are responsible for respiratory disease and diarrhea in cattle worldwide. The Norwegian control program against these infections is based on herd-level diagnosis using a new multiplex immunoassay. The objective of this study...

  3. An experimental infection model for reproduction of calf pneumonia with bovine respiratory syncytial virus (BRSV) based on one combined exposure of calves

    DEFF Research Database (Denmark)

    Tjørnehøj, Kirsten; Uttenthal, Åse; Viuff, B.

    2003-01-01

    Bovine respiratory syncytial virus (BRSV) has been recognised as an important pathogen in calf pneumonia for 30 years, but surprisingly few effective infection models for studies of the immune response and the pathogenesis in the natural host have been established. We present a reproducible...

  4. Experiments toward the development of a radioimmunoassay for the detection of serum antibodies for the respiratory syncytial virus

    International Nuclear Information System (INIS)

    Heizmann, W.R.

    1982-01-01

    In order to detect an infection by the respiratory syncytial virus (RSV) quickly and safely, a radioimmunassay (RIA) should be developed. Various antigen preparations were compared to one another. The immune serums used in the RIA came from guinea pigs with a RSV antibody titer of up to 320 in the complement binding reaction. A number of observations lead to the discussion of the possibility of the formation (incomplete) of cross-reactive antibodies between virus and host cell. This hypothesis could be well supported through references in the literature. Under the assumption of the existence of cross-reactive antibodies, a further model of the pathogenesis of the RSV illness allows itself to be developed, which could be preceived as an illness with autoimmune components. With this model the varying courses of this disease in different age groups can be easily explained. (orig.) [de

  5. Respiratory syncytial virus hospitalization outcomes and costs of full-term and preterm infants.

    Science.gov (United States)

    McLaurin, K K; Farr, A M; Wade, S W; Diakun, D R; Stewart, D L

    2016-11-01

    Infection with respiratory syncytial virus (RSV), which causes lower respiratory tract infections, is the leading cause of hospitalization among children preterm and full-term infants without chronic lung disease or other high-risk conditions. This analysis used Truven Health Market Scan Multi-State Medicaid and Commercial Claims and Encounters databases, which contain a combined 4 million births from 2003 to 2013. Infants with comorbid conditions associated with increased risk for RSV infection were excluded. Infants were classified as preterm (position. Costs of RSV hospitalizations were captured and reported in 2014 USD. Inpatient claims for RSV hospitalizations were evaluated for the presence of codes indicating admission to the intensive care unit (ICU), use of mechanical ventilation (MV) and length of stay. These three measures were used to describe hospital severity. Chronologic age at the time of RSV hospitalization was also captured. Data were summarized and no statistical comparisons were conducted. There were 1 683 188 infants insured through Medicaid and 1 663 832 infants insured through commercial plans born from 1 July 2003 to 30 June 2013. Of those, 10.8 and 8.8% in each database, respectively, were born prematurely. There were 29 967 Medicaid-insured infants and 16 310 commercially insured infants with an RSV hospitalization during their first year of life. Mean first-year RSV hospitalization costs were higher for preterm infants, ranging from $8324 and $10 570 for full-term infants to $15 839 and $19 931 for preterm infants 33-34 wGA, and to $39 354 and $40 813 for preterm infants preterm infants, with longer lengths of stay, a higher proportion of infants admitted to the intensive care unit (ICU) and increased use of MV compared with full-term infants. Mean costs of RSV hospitalizations with a PICU admission ranged from approximately $35 000 to $89 000. In both Medicaid and commercial groups, costs were greater for

  6. Altered cardiac rhythm in infants with bronchiolitis and respiratory syncytial virus infection.

    Science.gov (United States)

    Esposito, Susanna; Salice, Patrizia; Bosis, Samantha; Ghiglia, Silvia; Tremolati, Elena; Tagliabue, Claudia; Gualtieri, Laura; Barbier, Paolo; Galeone, Carlotta; Marchisio, Paola; Principi, Nicola

    2010-10-24

    Although the most frequent extra-pulmonary manifestations of respiratory syncytial virus (RSV) infection involve the cardiovascular system, no data regarding heart function in infants with bronchiolitis associated with RSV infection have yet been systematically collected. The aim of this study was to verify the real frequency of heart involvement in patients with bronchiolitis associated with RSV infection, and whether infants with mild or moderate disease also risk heart malfunction. A total of 69 otherwise healthy infants aged 1-12 months with bronchiolitis hospitalised in standard wards were enrolled. Pernasal flocked swabs were performed to collect specimens for the detection of RSV by real-time polymerase chain reaction, and a blood sample was drawn to assess troponin I concentrations. On the day of admission, all of the infants underwent 24-hour Holter ECG monitoring and a complete heart evaluation with echocardiography. Patients were re-evaluated by investigators blinded to the etiological and cardiac findings four weeks after enrollment. Regardless of their clinical presentation, sinoatrial blocks were identified in 26/34 RSV-positive patients (76.5%) and 1/35 RSV-negative patients (2.9%) (p < 0.0001). The blocks recurred more than three times over 24 hours in 25/26 RSV-positive patients (96.2%) and none of the RSV-negative infants. Mean and maximum heart rates were significantly higher in the RSV-positive infants (p < 0.05), as was low-frequency power and the low and high-frequency power ratio (p < 0.05). The blocks were significantly more frequent in the children with an RSV load of ≥100,000 copies/mL than in those with a lower viral load (p < 0.0001). Holter ECG after 28 ± 3 days showed the complete regression of the heart abnormalities. RSV seems associated with sinoatrial blocks and transient rhythm alterations even when the related respiratory problems are mild or moderate. Further studies are needed to clarify the mechanisms of these rhythm

  7. [Respiratory syncytial virus (RSV) infections in the pediatric teaching hospital Charles de Gaulle of Ouagadougou, Burkina Faso].

    Science.gov (United States)

    Ouédraogo Yugbaré, S O; Ouédraogo, R; Nenebi, A; Traoré, B; Congo, L; Yonli, F; Kima, D; Bonané, P; Yé, D; Plantier, J-C; Vabret, A; Marguet, C; Gueudin, M

    2016-02-01

    Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic.

  8. Spatial patterns of Bovine Corona Virus and Bovine Respiratory Syncytial Virus in the Swedish beef cattle population

    Directory of Open Access Journals (Sweden)

    Björkman Camilla

    2010-05-01

    Full Text Available Abstract Background Both bovine coronavirus (BCV and bovine respiratory syncytial virus (BRSV infections are currently wide-spread in the Swedish dairy cattle population. Surveys of antibody levels in bulk tank milk have shown very high nationwide prevalences of both BCV and BRSV, with large variations between regions. In the Swedish beef cattle population however, no investigations have yet been performed regarding the prevalence and geographical distribution of BCV and BRSV. A cross-sectional serological survey for BCV and BRSV was carried out in Swedish beef cattle to explore any geographical patterns of these infections. Methods Blood samples were collected from 2,763 animals located in 2,137 herds and analyzed for presence of antibodies to BCV and BRSV. Moran's I was calculated to assess spatial autocorrelation, and identification of geographical cluster was performed using spatial scan statistics. Results Animals detected positive to BCV or BRSV were predominately located in the central-western and some southern parts of Sweden. Moran's I indicated global spatial autocorrelation. BCV and BRSV appeared to be spatially related: two areas in southern Sweden (Skaraborg and Skåne had a significantly higher prevalence of BCV (72.5 and 65.5% respectively; almost the same two areas were identified as being high-prevalence clusters for BRSV (69.2 and 66.8% respectively. An area in south-east Sweden (Kronoberg-Blekinge had lower prevalences for both infections than expected (23.8 and 20.7% for BCV and BRSV respectively. Another area in middle-west Sweden (Värmland-Dalarna had also a lower prevalence for BRSV (7.9%. Areas with beef herd density > 10 per 100 km2 were found to be at significantly higher risk of being part of high-prevalence clusters. Conclusion These results form a basis for further investigations of between-herds dynamics and risk factors for these infections in order to design effective control strategies.

  9. Identification of cellular proteins that interact with Newcastle Disease Virus and human Respiratory Syncytial Virus by a two-dimensional virus overlay protein binding assay (VOPBA).

    Science.gov (United States)

    Holguera, Javier; Villar, Enrique; Muñoz-Barroso, Isabel

    2014-10-13

    Although it is well documented that the initial attachment receptors for Newcastle Disease Virus (NDV) and Respiratory Syncytial Virus (RSV) are sialic acid-containing molecules and glycosaminoglycans respectively, the exact nature of the receptors for both viruses remains to be deciphered. Moreover, additional molecules at the host cell surface might be involved in the entry mechanism. With the aim of identifying the cellular proteins that interact with NDV and RSV at the cell surface, we performed a virus overlay protein binding assay (VOPBA). Cell membrane lysates were separated by two dimensional (2D) gel electrophoresis and electrotransferred to PVDF membranes, after which they were probed with high viral concentrations. NDV interacted with a Protein Disulfide Isomerase from chicken fibroblasts. In the case of RSV, we detected 15 reactive spots, which were identified as six different proteins, of which nucleolin was outstanding. We discuss the possible role of PDI and nucleolin in NDV and RSV entry, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Establishing presence of antibodies against bovine respiratory syncytial virus (BRSV, parainfluenza virus 3 (PI3 and bovine herpesvirus 1 (BHV 1 in blood serum of cattle using indirect immunoenzyme probe

    Directory of Open Access Journals (Sweden)

    Šamanc Horea

    2009-01-01

    Full Text Available A total of 92 samples of bovine blood serum were examined for the presence of antibodies against the bovine respiratory syncytial virus using indirect immunoenzyme probe - iELISA. Specific antibodies against the bovine respiratory syncytial virus (BRSV were established in 46, or 50% blood serum samples. Investigations of the 92 blood serum samples of cattle for the presence of antibodies against the parainfluenza virus 3 (PI 3, revealed their presence in 77, or 83.69% of the samples, and the presence of antibodies against the bovine herpesvirus 1 (BHV 1 was established in 19, or 20.65% of the samples.

  11. Prevention of respiratory syncytial virus infections Prevenção das infecções pelo vírus sincicial respiratório

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2001-06-01

    Full Text Available Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia, and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.Em todo o mundo, o vírus sincicial respiratório é o principal agente de infecções agudas das vias aéreas baixas em lactentes jovens e crianças. Aos dois anos de idade, praticamente todas as crianças já foram infectadas, e as reinfeções são comuns

  12. A Bayesian SIRS model for the analysis of respiratory syncytial virus in the region of Valencia, Spain.

    Science.gov (United States)

    Corberán-Vallet, Ana; Santonja, Francisco J

    2014-09-01

    We present a Bayesian stochastic susceptible-infected-recovered-susceptible (SIRS) model in discrete time to understand respiratory syncytial virus dynamics in the region of Valencia, Spain. A SIRS model based on ordinary differential equations has also been proposed to describe RSV dynamics in the region of Valencia. However, this continuous-time deterministic model is not suitable when the initial number of infected individuals is small. Stochastic epidemic models based on a probability of disease transmission provide a more natural description of the spread of infectious diseases. In addition, by allowing the transmission rate to vary stochastically over time, the proposed model provides an improved description of RSV dynamics. The Bayesian analysis of the model allows us to calculate both the posterior distribution of the model parameters and the posterior predictive distribution, which facilitates the computation of point forecasts and prediction intervals for future observations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Decrease in formalin-inactivated respiratory syncytial virus (FI-RSV enhanced disease with RSV G glycoprotein peptide immunization in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Gertrud U Rey

    Full Text Available Respiratory syncytial virus (RSV is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study.

  14. Human respiratory syncytial virus non-structural protein NS1 modifies miR-24 expression via transforming growth factor-β

    Science.gov (United States)

    Bakre, Abhijeet; Wu, Weining; Hiscox, Julian; Spann, Kirsten; Teng, Michael N.

    2015-01-01

    Human respiratory syncytial virus (RSV) is a major health challenge in the young and elderly owing to the lack of a safe and effective vaccine and proven antiviral drugs. Understanding the mechanisms by which viral genes and proteins modulate the host response to infection is critical for identifying novel disease intervention strategies. In this study, the RSV non-structural protein NS1 was shown to suppress miR-24 expression during infection. Lack of NS1 was linked to increased expression of miR-24, whilst NS1 overexpression suppressed miR-24 expression. NS1 was found to induce Kruppel-like factor 6 (KLF6), a transcription factor that positively regulates the transforming growth factor (TGF)-β pathway to induce cell cycle arrest. Silencing of KLF6 led to increased miR-24 expression via downregulation of TGF-β. Treatment with exogenous TGF-β suppressed miR-24 expression and induced KLF6. Confocal microscopy showed co-localization of KLF6 and RSV NS1. These findings indicated that RSV NS1 interacts with KLF6 and modulates miR-24 expression and TGF-β, which facilitates RSV replication. PMID:26253191

  15. Cell fusion assay by expression of respiratory syncytial virus (RSV) fusion protein to analyze the mutation of palivizumab-resistant strains.

    Science.gov (United States)

    Yasui, Yosuke; Yamaji, Yoshiaki; Sawada, Akihito; Ito, Takashi; Nakayama, Tetsuo

    2016-05-01

    Respiratory syncytial virus (RSV) consists of fusion (F), glyco (G), and small hydrophobic (SH) proteins as envelope proteins, and infects through cell fusion. F protein is expressed on the surface of infected cells, and induces cell fusion. In the present report, expression plasmids of the F, G and SH proteins were constructed and cell fusion activity was investigated under T7 RNA polymerase. F protein alone induced cell fusion at a lower concentration than previously reported, and co-expression of F and SH proteins induced cell fusion more efficiently than F protein alone. Palivizumab is the only prophylactic agent against RSV infection. Palivizumab-resistant strains having mutations of the F protein of K272E and S275F were reported. These mutations were introduced into an F-expression plasmid, and exhibited no inhibition of cell fusion with palivizumab. Among the RSV F protein mutants, N276S has been reported to have partial resistance against palivizumab, but the F expression plasmid with the N276S mutation showed a reduction in cell fusion in the presence of palivizumab, showing no resistance to palivizumab. The present expression system was useful for investigating the mechanisms of RSV cell fusion. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Bovine parainfluenza virus type 3 (PIV3) expressing the respiratory syncytial virus (RSV) attachment and fusion proteins protects hamsters from challenge with human PIV3 and RSV.

    Science.gov (United States)

    Haller, Aurelia A; Mitiku, Misrach; MacPhail, Mia

    2003-08-01

    Parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) are the main causes of ubiquitous acute respiratory diseases of infancy and early childhood, causing 20-25 % of pneumonia and 45-50 % of bronchiolitis in hospitalized children. The primary goal of this study was to create an effective and safe RSV vaccine based on utilizing attenuated bovine PIV3 (bPIV3) as a virus vector backbone. bPIV3 had been evaluated in human clinical trials and was shown to be attenuated and immunogenic in children as young as 2 months of age. The ability of bPIV3 to function as a virus vaccine vector was explored further by introducing the RSV attachment (G) and fusion (F) genes into the bPIV3 RNA genome. The resulting virus, bPIV3/RSV(I), contained an insert of 2900 nt, comprising two translationally competent transcription units. Despite this increase in genetic material, the virus replicated to high titres in Vero cells. This recombinant virus expressed the RSV G and F proteins sufficiently to evoke a protective immune response in hamsters upon challenge with RSV or human PIV3 and to elicit RSV neutralizing and PIV3 haemagglutinin inhibition serum antibodies. In effect, a bivalent vaccine was produced that could protect vaccinees from RSV as well as PIV3. Such a vaccine would vastly reduce the respiratory disease burden, the associated hospitalization costs and, most importantly, decrease morbidity and mortality of infants, immunocompromised individuals and the elderly.

  17. Genetic variability of respiratory syncytial virus A in hospitalized children in the last five consecutive winter seasons in Central Spain.

    Science.gov (United States)

    Calderón, Ana; Pozo, Francisco; Calvo, Cristina; García-García, Mluz; González-Esguevillas, Mónica; Molinero, Mar; Casas, Inmaculada

    2017-05-01

    Human respiratory syncytial virus group A (RSV-A) was detected in symptomatic hospital attended children in Central Spain for a continuous time period, September 2010 to April 2015. In order to accurately describe the epidemiology of this virus, the genetic diversity of the complete G gene and the clinical manifestations observed were jointly analyzed. Out of 3,011 respiratory specimens taken from 2,308 children, 640 were positive to RSV (21.3%) and 405 were RSV-A (63.2%). Complete G gene sequences of 166 randomly selected RSV-A virus identified NA1 and ON1 genotypes. In 2011-2012, ON1 emerged sporadically and become dominant in 2012-2013 with 38 cases (70%). In 2014-2015, all the 44 sequences contained the 72-nt duplication (100%). Clinical diagnosis of children with ON1 genotype were bronchiolitis in 55 (62.5%), recurrent wheezing or asthma exacerbations in 22 (25%), laryngotracheobronchitis in 3 (3.4%), and upper respiratory tract infections in eight. Results showed replacement and substitution of circulating NA1 genotype with the new ON1 genotype. Nevertheless, at this stage, none of the RSV-A genotypes identified have resulted in significant clinical differences. The amino acid composition of the complete G gene ON1 sequences demonstrated an accumulation of single changes not related with different clinical presentation. J. Med. Virol. 89:767-774, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Non-typeable Haemophilus influenzae protects human airway epithelial cells from a subsequent respiratory syncytial virus challenge.

    Science.gov (United States)

    Hartwig, Stacey M; Ketterer, Margaret; Apicella, Michael A; Varga, Steven M

    2016-11-01

    Respiratory syncytial virus (RSV) and the common commensal and opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) both serve as a frequent cause of respiratory infection in children. Although it is well established that some respiratory viruses can increase host susceptibility to secondary bacterial infections, few studies have examined how commensal bacteria could influence a secondary viral response. Here, we examined the impact of NTHi exposure on a subsequent RSV infection of human bronchial epithelial cells (16HBE14o-). Co-culture of 16HBE14o- cells with NTHi resulted in inhibition of viral gene expression following RSV infection. 16HBE14o- cells co-cultured with heat-killed NTHi failed to protect against an RSV infection, indicating that protection requires live bacteria. However, NTHi did not inhibit influenza A virus replication, indicating that NTHi-mediated protection was RSV-specific. Our data demonstrates that prior exposure to a commensal bacterium such as NTHi can elicit protection against a subsequent RSV infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Bovine respiratory syncytial virus seroprevalence and risk factors in feedlot cattle from Córdoba and Santa Fe, Argentina.

    Science.gov (United States)

    Ferella, Alejandra; Pérez Aguirreburualde, María Sol; Margineda, Carlos; Aznar, Natalia; Sammarruco, Ayelen; Dus Santos, María Jose; Mozgovoj, Marina

    2017-11-30

    Bovine respiratory syncytial virus (BRSV) is one of the causative agents of respiratory disease in cattle all over the world, leading to important economic losses. The aim of this work was to determine the seroprevalence of BRSV in feedlot cattle of Argentina and the risk factors associated with the disease. Results showed a high individual seroprevalence of 78.64% (95% confidence interval adjusted [CI]=66.55-90.75%) against the virus. Positive association was found between the presence of high BRSV neutralizing antibody titers, and the following risk factors: cattle age, source of animals, presence of clinical respiratory signs and herd size. This work contributes to updating the understanding of its epidemiology in Argentinean feedlots and poses the need for reevaluating vaccination strategies against this virus in order to control infection and its impact on productivity. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. [How I manage respiratory syncytial virus, human herpesvirus 6 and adenovirus reactivation or infection after allogeneic stem cell transplantation: a report of the SFGM-TC].

    Science.gov (United States)

    Deconinck, E; Dalle, J-H; Berceanu, A; Chevallier, P; Duléry, R; Garnier, A; Huynh, A; Labussière-Wallet, H; Nguyen Quoc, S; Dewilde, A; Ramon, P; Yakoub-Agha, I

    2013-08-01

    In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of virus respiratory syncytial virus (RSV), human herpes virus 6 (HHV6) or adenovirus allogeneic Stem Cell Transplantation. Copyright © 2013. Published by Elsevier SAS.

  1. Host cell entry of respiratory syncytial virus involves macropinocytosis followed by proteolytic activation of the F protein.

    Directory of Open Access Journals (Sweden)

    Magdalena Anna Krzyzaniak

    Full Text Available Respiratory Syncytial Virus (RSV is a highly pathogenic member of the Paramyxoviridae that causes severe respiratory tract infections. Reports in the literature have indicated that to infect cells the incoming viruses either fuse their envelope directly with the plasma membrane or exploit clathrin-mediated endocytosis. To study the entry process in human tissue culture cells (HeLa, A549, we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. A variety of perturbants were employed to characterize the cellular processes involved. We found that immediately after binding to cells RSV activated a signaling cascade involving the EGF receptor, Cdc42, PAK1, and downstream effectors. This led to a series of dramatic actin rearrangements; the cells rounded up, plasma membrane blebs were formed, and there was a significant increase in fluid uptake. If these effects were inhibited using compounds targeting Na⁺/H⁺ exchangers, myosin II, PAK1, and other factors, no infection was observed. The RSV was rapidly and efficiently internalized by an actin-dependent process that had all hallmarks of macropinocytosis. Rather than fusing with the plasma membrane, the viruses thus entered Rab5-positive, fluid-filled macropinosomes, and fused with the membranes of these on the average 50 min after internalization. Rab5 was required for infection. To find an explanation for the endocytosis requirement, which is unusual among paramyxoviruses, we analyzed the fusion protein, F, and could show that, although already cleaved by a furin family protease once, it underwent a second, critical proteolytic cleavage after internalization. This cleavage by a furin-like protease removed a small peptide from the F1 subunits, and made the virus infectious.

  2. Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children.

    Science.gov (United States)

    Mazur, Natalie I; Bont, Louis; Cohen, Adam L; Cohen, Cheryl; von Gottberg, Anne; Groome, Michelle J; Hellferscee, Orienka; Klipstein-Grobusch, Kerstin; Mekgoe, Omphile; Naby, Fathima; Moyes, Jocelyn; Tempia, Stefano; Treurnicht, Florette K; Venter, Marietje; Walaza, Sibongile; Wolter, Nicole; Madhi, Shabir A

    2017-02-15

    Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged HIV-uninfected children with respiratory syncytial virus (RSV)-associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39-1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6-7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0-4.5; P = .05) compared with RSV monoinfection. RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. One-step multiplex real time RT-PCR for the detection of bovine respiratory syncytial virus, bovine herpesvirus 1 and bovine parainfluenza virus 3.

    Science.gov (United States)

    Thonur, Leenadevi; Maley, Madeleine; Gilray, Janice; Crook, Tara; Laming, Ellie; Turnbull, Dylan; Nath, Mintu; Willoughby, Kim

    2012-03-28

    Detection of respiratory viruses in veterinary species has traditionally relied on virus detection by isolation or immunofluorescence and/or detection of circulating antibody using ELISA or serum neutralising antibody tests. Multiplex real time PCR is increasingly used to diagnose respiratory viruses in humans and has proved to be superior to traditional methods. Bovine respiratory disease (BRD) is one of the most common causes of morbidity and mortality in housed cattle and virus infections can play a major role. We describe here a one step multiplex reverse transcriptase quantitative polymerase chain reaction (mRT-qPCR) to detect the viruses commonly implicated in BRD. A mRT-qPCR assay was developed and optimised for the simultaneous detection of bovine respiratory syncytial virus (BRSV), bovine herpes virus type 1 (BoHV-1) and bovine parainfluenza virus type 3 (BPI3 i & ii) nucleic acids in clinical samples from cattle. The assay targets the highly conserved glycoprotein B gene of BoHV-1, nucleocapsid gene of BRSV and nucleoprotein gene of BPI3. This mRT-qPCR assay was assessed for sensitivity, specificity and repeatability using in vitro transcribed RNA and recent field isolates. For clinical validation, 541 samples from clinically affected animals were tested and mRT-qPCR result compared to those obtained by conventional testing using virus isolation (VI) and/or indirect fluorescent antibody test (IFAT). The mRT-qPCR assay was rapid, highly repeatable, specific and had a sensitivity of 97% in detecting 102 copies of BRSV, BoHV-1 and BPI3 i & ii. This is the first mRT-qPCR developed to detect the three primary viral agents of BRD and the first multiplex designed using locked nucleic acid (LNA), minor groove binding (MGB) and TaqMan probes in one reaction mix. This test was more sensitive than both VI and IFAT and can replace the aforesaid methods for virus detection during outbreaks of BRD.

  4. Immunoprotectivity of HLA-A2 CTL peptides derived from respiratory syncytial virus fusion protein in HLA-A2 transgenic mouse.

    Directory of Open Access Journals (Sweden)

    Hsiao-Yun Shao

    Full Text Available Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV-induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F of respiratory syncytial virus (RSV and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33-41, 13 (F214-222, 14 (F273-281, and 23 (F559-567, were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-γ and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg mice pre-immunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18 but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine.

  5. Development of TaqMan RT-qPCR for the detection of type A human respiratory syncytial virus.

    Science.gov (United States)

    Abdel-Moneim, Ahmed S; Shehab, Gaber M; Alsulaimani, Adnan A; Al-Malky, Mater I R

    2017-06-01

    The human respiratory syncytial virus is a common respiratory pathogen in children. Improved diagnosis of the virus is dependent on the development of tools for the rapid detection and estimation of the viral loads. In the current study, RT-qPCR using TaqMan hydrolysis probe based on the F gene detection was developed to identify and quantify hRSV in clinical samples. The assay was validated by comparing the results with a commercially available RT-qPCR kit. The newly developed assay was sensitive in detecting hRSV positive samples (59/126) which were equivalent to those detected by the commercial kit (57/126) with a detection limit of 1 × 10 2 copies/mL. A high correlation was found between the results of the newly developed assay and the commercial one. It was concluded that the newly developed RT-qPCR assay can be used as a sensitive detection tool for hRSV-A. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Monitoring epidemic viral respiratory infections using one-step real-time triplex RT-PCR targeting influenza A and B viruses and respiratory syncytial virus.

    Science.gov (United States)

    Papillard-Marechal, Solesne; Enouf, Vincent; Schnuriger, Aurélie; Vabret, Astrid; Macheras, Edouard; Rameix-Welti, Marie-Anne; Page, Bernard; Freymuth, François; van der Werf, Sylvie; Garbarg-Chenon, Antoine; Chevallier, Bertrand; Gaillard, Jean-Louis; Gault, Elyanne

    2011-04-01

    Rapid and specific diagnosis of influenza A/B and respiratory syncytial virus (RSV) viruses is needed for optimal management of patients with acute respiratory infections. In this study, a one-step triplex real-time RT-PCR assay was developed for rapid diagnosis of influenza A/B and RSV infections to optimize diagnosis efficiency of acute respiratory infections. Cell-culture supernatants and clinical samples were used to evaluate specificity and sensitivity of the assay. The assay was used routinely during two winter epidemics for testing respiratory specimens from 2,417 patients. The limit of detection in cell-culture supernatant was 1-10 plaque forming units/input (influenza A/B) and 2 × 10(-2) 50% tissue culture infectious dose/input (RSV). In clinical samples, the assay was as sensitive as commercial molecular assays for the detection of each influenza A/B and RSV (Flu-A/B and RSV-A/B r-gene™) individually, and far more sensitive than antigen detection. During the winter 2008-2009, the assay identified 145 RSV, 42 influenza A, and one mixed RSV-influenza A infections among 298 patients. The next winter, the assay was used in two independent hospital laboratory settings. 776 patients were tested in one hospital and 1,343 in the other, resulting in 184 and 501 RSV, 133 and 150 influenza A, and 1 and 11 mixed RSV-influenza A infections, respectively, being detected. This new user-friendly assay allows rapid (within hours), effective molecular diagnosis of single or mixed infections involving influenza A (including seasonal A H1N1 and H3N2, and A(H1N1) 2009), influenza B, and RSV(A/B). The assay is very valuable for managing patients during winter epidemics when influenza and respiratory syncytial viruses co-circulate. Copyright © 2011 Wiley-Liss, Inc.

  7. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate.

    Directory of Open Access Journals (Sweden)

    Jerome Deval

    2015-06-01

    Full Text Available Respiratory syncytial virus (RSV causes severe lower respiratory tract infections, yet no vaccines or effective therapeutics are available. ALS-8176 is a first-in-class nucleoside analog prodrug effective in RSV-infected adult volunteers, and currently under evaluation in hospitalized infants. Here, we report the mechanism of inhibition and selectivity of ALS-8176 and its parent ALS-8112. ALS-8176 inhibited RSV replication in non-human primates, while ALS-8112 inhibited all strains of RSV in vitro and was specific for paramyxoviruses and rhabdoviruses. The antiviral effect of ALS-8112 was mediated by the intracellular formation of its 5'-triphosphate metabolite (ALS-8112-TP inhibiting the viral RNA polymerase. ALS-8112 selected for resistance-associated mutations within the region of the L gene of RSV encoding the RNA polymerase. In biochemical assays, ALS-8112-TP was efficiently recognized by the recombinant RSV polymerase complex, causing chain termination of RNA synthesis. ALS-8112-TP did not inhibit polymerases from host or viruses unrelated to RSV such as hepatitis C virus (HCV, whereas structurally related molecules displayed dual RSV/HCV inhibition. The combination of molecular modeling and enzymatic analysis showed that both the 2'F and the 4'ClCH2 groups contributed to the selectivity of ALS-8112-TP. The lack of antiviral effect of ALS-8112-TP against HCV polymerase was caused by Asn291 that is well-conserved within positive-strand RNA viruses. This represents the first comparative study employing recombinant RSV and HCV polymerases to define the selectivity of clinically relevant nucleotide analogs. Understanding nucleotide selectivity towards distant viral RNA polymerases could not only be used to repurpose existing drugs against new viral infections, but also to design novel molecules.

  8. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  9. Th17 cytokines are critical for respiratory syncytial virus-associated airway hyperreponsiveness through regulation by complement C3a and tachykinins.

    Science.gov (United States)

    Bera, Monali M; Lu, Bao; Martin, Thomas R; Cui, Shun; Rhein, Lawrence M; Gerard, Craig; Gerard, Norma P

    2011-10-15

    Respiratory syncytial virus (RSV) infection is associated with serious lung disease in infants and immunocompromised individuals and is linked to development of asthma. In mice, acute RSV infection causes airway hyperresponsiveness (AHR), inflammation, and mucus hypersecretion. Infected cells induce complement activation, producing the anaphylatoxin C3a. In this paper, we show RSV-infected wild-type mice produce Th17 cytokines, a response not previously associated with viral infections. Mice deficient in the C3aR fail to develop AHR following acute RSV infection, and production of Th17 cytokines was significantly attenuated. Tachykinin production also has been implicated in RSV pathophysiology, and tachykinin receptor-null mice were similarly protected from developing AHR. These animals were also deficient in production of Th17 cytokines. Tachykinin release was absent in mice deficient in C3aR, whereas C3a levels were unchanged in tachykinin receptor-null animals. Thus, our data reveal a crucial sequence following acute RSV infection where initial C3a production causes tachykinin release, followed by activation of the IL-17A pathway. Deficiency of either receptor affords protection from AHR, identifying two potential therapeutic targets.

  10. Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Yuanhui [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); He, Jinsheng, E-mail: jshhe@bjtu.edu.cn [College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Zheng, Xianxian [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wu, Qiang [Department of Pathology, Anhui Medical University, Hefei, Anhui, 230032 (China); Zhang, Mei; Wang, Xiaobo [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wang, Yan [Department of Pathology, Anhui Medical University, Hefei, Anhui, 230032 (China); Xie, Can; Tang, Qian; Wei, Wei [Department of Immunology, Anhui Medical University, Hefei, Anhui, 230032 (China); Wang, Min; Song, Jingdong; Qu, Jianguo [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); Zhang, Ying; Wang, Xin [College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China); Hong, Tao [Institute of Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 (China); College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing, 100044 (China)

    2009-04-17

    Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection.

  11. Chimeric bovine/human parainfluenza virus type 3 expressing respiratory syncytial virus (RSV) F glycoprotein: effect of insert position on expression, replication, immunogenicity, stability, and protection against RSV infection.

    Science.gov (United States)

    Liang, Bo; Munir, Shirin; Amaro-Carambot, Emerito; Surman, Sonja; Mackow, Natalie; Yang, Lijuan; Buchholz, Ursula J; Collins, Peter L; Schaap-Nutt, Anne

    2014-04-01

    A recombinant chimeric bovine/human parainfluenza type 3 virus (rB/HPIV3) vector expressing the respiratory syncytial virus (RSV) fusion F glycoprotein previously exhibited disappointing levels of RSV F immunogenicity and genetic stability in children (D. Bernstein et al., Pediatr. Infect. Dis. J. 31:109-114, 2012; C.-F. Yang et al., Vaccine 31:2822-2827, 2013). To investigate parameters that might affect vaccine performance and stability, we constructed and characterized rB/HPIV3 viruses expressing RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions. There was a 30- to 69-fold gradient in RSV F expression from the first to the sixth position. The inserts moderately attenuated vector replication in vitro and in the upper and lower respiratory tracts of hamsters: this was not influenced by the level of RSV F expression and syncytium formation. Surprisingly, inserts in the second, third, and sixth positions conferred increased temperature sensitivity: this was greatest for the third position and was the most attenuating in vivo. Each rB/HPIV3 vector induced a high titer of neutralizing antibodies in hamsters against RSV and HPIV3. Protection against RSV challenge was greater for position 2 than for position 6. Evaluation of insert stability suggested that RSV F is under selective pressure to be silenced during vector replication in vivo, but this was not exacerbated by a high level of RSV F expression and generally involved a small percentage of recovered vector. Vector passaged in vitro accumulated mutations in the HN open reading frame, causing a dramatic increase in plaque size that may have implications for vaccine production and immunogenicity. The research findings presented here will be instrumental for improving the design of a bivalent pediatric vaccine for respiratory syncytial virus and parainfluenza virus type 3, two major causes of severe respiratory tract infection in infants and young children. Moreover, this

  12. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV: consequences of deficient interferon-dependent antiviral defense

    Directory of Open Access Journals (Sweden)

    Hubbard Gene B

    2011-01-01

    Full Text Available Abstract Background Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells. Methods The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors Results We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/β-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The

  13. Design and Characterization of Epitope-Scaffold Immunogens That Present the Motavizumab Epitope from Respiratory Syncytial Virus

    Energy Technology Data Exchange (ETDEWEB)

    McLellan, Jason S.; Correia, Bruno E.; Chen, Man; Yang, Yongping; Graham, Barney S.; Schief, William R.; Kwong, Peter D. (UWASH); (NIH)

    2012-06-28

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 {angstrom} resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required.

  14. Bovine respiratory disease associated with Histophilus somni and bovine respiratory syncytial virus in a beef cattle feedlot from Southeastern Brazil

    Directory of Open Access Journals (Sweden)

    Selwyn Arligton Headley

    2017-03-01

    Full Text Available Bovine respiratory disease (BRD is a complex multifactorial and multi-etiological disease entity that is responsible for the morbidity and mortality particularly in feedlot cattle from North America. Information relative to the occurrence of BRD in Brazil and the associated infectious agents are lacking. This study investigated the participation of infectious agents of BRD in a beef cattle feedlot from Southeastern Brazil. Nasopharyngeal swabs of 11% (10/90 of cattle (n, 450 with clinical manifestations of respiratory distress were analyzed by targeting specific genes of the principal infectious pathogens of BRD. In addition, pulmonary fragments of one the animals that died were collected for histopathological and molecular diagnoses. The nucleic acids of Histophilus somni and bovine respiratory syncytial virus (BRSV were identified in 20% (2/10 of the nasopharyngeal swabs of the animals with respiratory distress; another contained only BRSV RNA. Moreover, the nucleic acids of both infectious agents were amplified from the pulmonary fragments of the animal that died with histopathological evidence of bronchopneumonia and interstitial pneumonia; the nasopharyngeal swab of this animal also contained the nucleic acids of both pathogens. Additionally, all PCR and/or RT-PCR assays designed to detect the specific genes of Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, bovine viral diarrhea virus, bovine herpesvirus -1, bovine parainfluenza virus-3, and bovine coronavirus yielded negative results. Phylogenetic analyses suggest that the isolates of H. somni circulating in Brazil are similar to those identified elsewhere, while there seem to be diversity between the isolates of BRSV within cattle herds from different geographical locations of Brazil.

  15. Preclinical Characterization of PC786, an Inhaled Small-Molecule Respiratory Syncytial Virus L Protein Polymerase Inhibitor.

    Science.gov (United States)

    Coates, Matthew; Brookes, Daniel; Kim, Young-In; Allen, Heather; Fordyce, Euan A F; Meals, Elizabeth A; Colley, Thomas; Ciana, Claire-Lise; Parra, Guillaume F; Sherbukhin, Vladimir; Stockwell, Jennifer A; Thomas, Jennifer C; Hunt, S Fraser; Anderson-Dring, Lauren; Onions, Stuart T; Cass, Lindsey; Murray, Peter J; Ito, Kazuhiro; Strong, Pete; DeVincenzo, John P; Rapeport, Garth

    2017-09-01

    Although respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children, attempts to develop an effective therapy have so far proved unsuccessful. Here we report the preclinical profiles of PC786, a potent nonnucleoside RSV L protein polymerase inhibitor, designed for inhalation treatment of RSV infection. PC786 demonstrated a potent and selective antiviral activity against laboratory-adapted or clinical isolates of RSV-A (50% inhibitory concentration [IC 50 ], <0.09 to 0.71 nM) and RSV-B (IC 50 , 1.3 to 50.6 nM), which were determined by inhibition of cytopathic effects in HEp-2 cells without causing detectable cytotoxicity. The underlying inhibition of virus replication was confirmed by PCR analysis. The effects of PC786 were largely unaffected by the multiplicity of infection (MOI) and were retained in the face of established RSV replication in a time-of-addition study. Persistent anti-RSV effects of PC786 were also demonstrated in human bronchial epithelial cells. In vivo intranasal once daily dosing with PC786 was able to reduce the virus load to undetectable levels in lung homogenates from RSV-infected mice and cotton rats. Treatment with escalating concentrations identified a dominant mutation in the L protein (Y1631H) in vitro In addition, PC786 potently inhibited RSV RNA-dependent RNA polymerase (RdRp) activity in a cell-free enzyme assay and minigenome assay in HEp-2 cells (IC 50 , 2.1 and 0.5 nM, respectively). Thus, PC786 was shown to be a potent anti-RSV agent via inhibition of RdRp activity, making topical treatment with this compound a novel potential therapy for the treatment of human RSV infections. Copyright © 2017 Coates et al.

  16. [Preliminary analysis on respiratory syncytial virus identified in children with acute respiratory infections in Tibet Autonomous Region, China].

    Science.gov (United States)

    Deng, Jie; Zhu, Ru-Nan; Qian, Yuan; Sun, Yu; Zhao, Lin-Qing; Wang, Fang; Wu, Hong; Shan, Min-Na; Deji, Mei-Duo

    2012-03-01

    To understand the role of respiratory syncytial virus (RSV) in children with acute respiratory infections (ARI) in Tibet Autonomous Region and the contribution of two major groups of RSV, nasopharyngeal aspirates (NPA) were collected from hospitalized children with ARI in Department of Pediatrics, Tibet People's Hospital in Lasa, Tibet from April to July in 2011 and tested for seven common respiratory viruses and human metapneumovirus (hMPV) by direct immunofluorescence assay (DFA). Total RNAs were extracted from RSV positive samples by DFA and reverse transcripted to cDNA. Nested-PCR was employed to determine the genogroups of RSV, which were confirmed by real time-PCR and sequence analysis for G protein encoding gene. The Characteristics and variations of G genes from RSV in this project were identified by sequence comparison with those G genes in GenBank. Out of 167 samples, 65 were positive for respiratory viruses with a total positive rate of 38.9%, including 45 (69.2%, 45/65)positive samples for RSV. Among 42 samples that were positive for RSV and genotyped, 40 were identified as group A and 2 as group B. Sequence analysis of full-length G genes for 7 RSV of group A indicated that all of these belonged to subgroup GA2. The nucleotide identities between RSVs from Tibet and prototype A2 strain were 90.7%-91.8%, with 86.5%-87.2% identities of amino acid. The mutations of amino acids were mainly located in both ends of a highly conserved region in the ectodomain of the G proteins. The data indicated that RSV was the most important viral etiologic agent of ARI in spring of 2011 in Tibet and group A of RSV was predominant during the study period. High divergence existed in the ectodomain of G proteins of RSVs from Tibet.

  17. The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years

    Directory of Open Access Journals (Sweden)

    Alfonsina Trento

    2017-11-01

    Full Text Available The influence of age and maternal antibodies on the antibody responses to human respiratory syncytial virus (hRSV glycoproteins in very young children has been a matter of controversy. Both, immaturity of the immune system at very early age and suppression of the host immune response by high level of maternal antibodies have been claimed to limit the host antibody response to virus infection and to jeopardize the use of hRSV vaccines under development in that age group. Hence, the antibody responses to the two major hRSV glycoproteins (F and G were evaluated in children younger than 2 years, hospitalized with laboratory confirmed hRSV bronchiolitis. A strong negative correlation was found between the titre of circulating ELISA antibodies directed against either prefusion or postfusion F in the acute phase, but not age, and their fold change at convalescence. These changes correlated also with the level of circulating neutralizing antibodies in sera. As reported in adults, most neutralizing antibodies in a subset of tested sera could not be depleted with postfusion F, suggesting that they were mostly directed against prefusion-specific epitopes. In contrast, a weak negative association was found for group-specific anti-G antibodies in the acute phase and their fold change at convalescence only after correcting for the antigenic group of the infecting virus. In addition, large discrepancies were observed in some individuals between the antibody responses specific for F and G glycoproteins. These results illustrate the complexity of the anti-hRSV antibody responses in children experiencing a primary severe infection and the influence of preexisting maternal antibodies on the host response, factors that should influence hRSV serological studies as well as vaccine development.

  18. Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study.

    Science.gov (United States)

    Higdon, Melissa M; Le, Tham; O'Brien, Katherine L; Murdoch, David R; Prosperi, Christine; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Scott, J Anthony G; Thea, Donald M; Awori, Juliet O; Baillie, Vicky L; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N; Driscoll, Amanda J; Ebruke, Bernard E; Endtz, Hubert P; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A; Moore, David P; Park, Daniel E; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D; Zeger, Scott L; Deloria Knoll, Maria; Madhi, Shabir A

    2017-06-15

    Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  19. Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology.

    Science.gov (United States)

    Wong, Terianne M; Petrovsky, Nikolai; Bissel, Stephanie J; Wiley, Clayton A; Ross, Ted M

    2016-08-02

    Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax™. Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which Advax TM adjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (∼10E+3pfu/g) in mice administered vaccine with either Advax TM adjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with Advax TM was similar to Imject Alum. Overall, RSV vaccine formulated with Advax TM had high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared

  20. Molecular characteristics and successful management of a respiratory syncytial virus outbreak among pediatric patients with hemato-oncological disease.

    Science.gov (United States)

    Baier, Claas; Haid, Sibylle; Beilken, Andreas; Behnert, Astrid; Wetzke, Martin; Brown, Richard J P; Schmitt, Corinna; Ebadi, Ella; Hansen, Gesine; Schulz, Thomas F; Pietschmann, Thomas; Bange, Franz-Christoph

    2018-01-01

    Respiratory syncytial virus (RSV) is responsible for upper and lower respiratory tract infection in adults and children. Especially immunocompromised patients are at high risk for a severe course of infection, and mortality is increased. Moreover RSV can spread in healthcare settings and can cause outbreaks. Herein we demonstrate the successful control and characteristics of a RSV outbreak that included 8 patients in our Department of Pediatric Hematology and Oncology. We performed an epidemiologic investigation and a molecular analysis of the outbreak strains. Moreover we present the outbreak control bundle and our concept for RSV screening in the winter season. RSV A and B strains caused the outbreak. RSV B strains affected 3 patients, 2 of whom were co-infected with RSV A. Exactly this RSV A strain was detected in another 5 patients. Our multimodal infection control bundle including prophylactic RSV screening was able to rapidly stop the outbreak. An infection control bundle in RSV outbreaks should address all potential transmission pathways. In pediatric settings the restriction of social activities might have a temporal negative impact on quality of life but helps to limit transmission opportunities. Molecular analysis allows better understanding of RSV outbreaks and, if done in a timely manner, might be helpful for guidance of infection control measures.

  1. A Preliminary Assessment of the Role of Ambient Nitric Oxide Exposure in Hospitalization with Respiratory Syncytial Virus Bronchiolitis

    Directory of Open Access Journals (Sweden)

    Nuredin I. Mohammed

    2016-06-01

    Full Text Available Some in vitro studies have indicated a possible link between respiratory syncytial virus (RSV infection and exposure to Nitric Oxide (NO. However, these studies used much higher NO concentrations than normally found in the ambient environment. This preliminary study explored whether an association was present with short-term exposure to NO in the environment. RSV-related admission data between November 2011 and February 2012 were obtained from Sheffield Children’s Hospital. The dates of admission were linked to contemporaneous ambient NO derived from sentinel air monitors. The case-crossover design was used to study the relationship between daily RSV admissions and NO, controlling for temperature and relative humidity. We found little evidence of association between daily RSV admission rates and exposure to ambient NO at different lags or average exposure across several lags. The findings should, however, be viewed with caution due to the low number of events observed during the time frame. It is possible that the apparent lack of association may be accounted for by the timing of the seasonal RSV epidemic in relation to peaks in NO concentrations. A larger study incorporating a wider range of RSV and NO peaks would determine whether said peaks enhanced the number of RSV hospitalizations in children.

  2. [Expression of heparanase in kidney of rats with respiratory syncytial virus nephropathy and its relationship with proteinurina].

    Science.gov (United States)

    Tao, Yu-Hong; Wang, Zheng; Zhou, Yan-Ru

    2014-03-01

    To explore the role of heparanase in the pathogenesis of respiratory syncytial virus (RSV) nephropathy in rats model. Twenty 150-200 g Sprague-Dawley (SD) rats (n = 5 per group) were inoculated with 6 x 10(6) PFU RSV and sacrificed on days 4, 8, 14 and 28 postinoculation (RSV4, RSV8, RSV14 and RSV29). Five SD rats inoculated with Dulbecco's minimum essential medium were served as normal control. The expression levels of heparanase protein and mRNA in the rat renal tissue of each group were determined by immunohistochemical staining and real-time quantitative RT-PCR respectively. The proteinurina was also measured and then the relationship between the expression level of heparanase and the 24-hour urinary protein was studied. The rats with RSV nephropathy exhibited higher proteinuria in comparison with normal rats, and the 24-hour urinary protein level was significantly different between each RSV nephropathy group (RSV14 > RSV8 > RSV28 > RSV4, P RSV8 > RSV4 > RSV28 , P < 0.05). There was a linear positive correlation between the expression level of renal heparanase mRNA and the quantity of 24-hour urinary protein (r = 0.725, P < 0.05). The increased expression of heparanase in kidney may be important to the loss of glomerular negative charge in glomerular basement membrane which is involved in the pathogenesis of RSV nephropathy in rats.

  3. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Viviane F Botosso

    2009-01-01

    Full Text Available Human respiratory syncytial virus (HRSV is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  4. Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, Kurt A.; Settembre, Ethan C.; Shaw, Christine A.; Dey, Antu K.; Rappuoli, Rino; Mandl, Christian W.; Dormitzer, Philip R.; Carfi, Andrea (Novartis)

    2012-02-07

    Respiratory syncytial virus (RSV), the main cause of infant bronchiolitis, remains a major unmet vaccine need despite more than 40 years of vaccine research. Vaccine candidates based on a chief RSV neutralization antigen, the fusion (F) glycoprotein, have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the prefusion and postfusion states, suggesting that postfusion F antigens might not efficiently elicit neutralizing antibodies. We have generated a homogeneous, stable, and reproducible postfusion RSV F immunogen that elicits high titers of neutralizing antibodies in immunized animals. The 3.2-{angstrom} X-ray crystal structure of this substantially complete RSV F reveals important differences from homology-based structural models. Specifically, the RSV F crystal structure demonstrates the exposure of key neutralizing antibody binding sites on the surface of the postfusion RSV F trimer. This unanticipated structural feature explains the engineered RSV F antigen's efficiency as an immunogen. This work illustrates how structural-based antigen design can guide the rational optimization of candidate vaccine antigens.

  5. Acute phase protein changes in calves during an outbreak of respiratory disease caused by bovine respiratory syncytial virus.

    Science.gov (United States)

    Orro, Toomas; Pohjanvirta, Tarja; Rikula, Ulla; Huovilainen, Anita; Alasuutari, Sakari; Sihvonen, Liisa; Pelkonen, Sinikka; Soveri, Timo

    2011-01-01

    Bovine acute phase proteins (APPs), lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), haptoglobin (Hp) and alpha(1)-acid glycoprotein (AGP) were evaluated as inflammatory markers during an outbreak of bovine respiratory disease (BRD) caused by bovine respiratory syncytial virus (BRSV). Calves (n = 10) presented mild to moderate signs of respiratory disease. Secondary bacterial infections, Pasteurella multocida and Mycoplasma dispar as major species, were detected in tracheobronchial lavage samples. Concentrations of SAA and LBP increased at week 1 had the highest values at week 3 and decreased at week 4 of outbreak. Some calves had high Hp concentrations at week 3, but AGP concentrations did not rise during respiratory disease. Higher SAA, LBP and Hp concentrations at a later stage of BRD (week 3) were associated with the low BRSV-specific IgG(1) production, suggesting that these calves had enhanced inflammatory response to the secondary bacterial infection. In conclusion, APPs (especially SAA and LBP) are sensitive markers of respiratory infection, and they may be useful to explore host response to the respiratory infections in clinical research. Copyright © 2009 Elsevier Ltd. All rights reserved.

  6. Nosocomial respiratory syncytial virus infections in the palivizumab-prophylaxis era with implications regarding high-risk infants.

    Science.gov (United States)

    Ashkenazi-Hoffnung, Liat; Dotan, Miri; Livni, Gilat; Amir, Jacob; Bilavsky, Efraim

    2014-09-01

    Although respiratory syncytial virus (RSV) infection continues to be a leading cause of infant hospitalization with a high transmission rate, recent data on nosocomial RSV infection are scarce. This study investigated the clinical and epidemiologic characteristics of nosocomial RSV infection in the palivizumab-prophylaxis era. The database of a tertiary pediatric medical center was searched for all hospitalized patients with RSV-positive respiratory disease in 2008-2010. Data were compared between patients with community-associated and nosocomial disease, and the qualification of the latter group for palivizumab was evaluated. Of the 873 children identified, 30 (3.4%) had a nosocomial infection. This group accounted for 0.06% of all admissions during the study period. The nosocomial infection group had higher rates of preterm birth and severe underlying disease than the community-associated RSV group and a longer mean hospital stay. The nosocomial infection group also had higher rates of intensive care unit admission and mechanical ventilation. Although 73% had underlying conditions, most (80%) did not qualify for RSV immunoprophylaxis, including 7 children (23%) with immune deficiency. Nosocomial RSV infection is a significant cause of morbidity among hospitalized infants, especially those with comorbidities and lengthy hospital stay, and is associated with a complicated clinical course. In addition to strict infection-control measures, extending palivizumab prophylaxis to additional selected high-risk populations should be considered. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  7. Past, Present and Future Approaches to the Prevention and Treatment of Respiratory Syncytial Virus Infection in Children.

    Science.gov (United States)

    Simões, Eric A F; Bont, Louis; Manzoni, Paolo; Fauroux, Brigitte; Paes, Bosco; Figueras-Aloy, Josep; Checchia, Paul A; Carbonell-Estrany, Xavier

    2018-03-01

    The REGAL (RSV Evidence - A Geographical Archive of the Literature) series has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This seventh and final publication covers the past, present and future approaches to the prevention and treatment of RSV infection among infants and children. A systematic review was undertaken of publications between January 1, 1995 and December 31, 2017 across PubMed, Embase and The Cochrane Library. Studies reporting data on the effectiveness and tolerability of prophylactic and therapeutic agents for RSV infection were included. Study quality and strength of evidence (SOE) were graded using recognized criteria. A further nonsystematic search of the published literature and Clinicaltrials.gov on antiviral therapies and RSV vaccines currently in development was also undertaken. The systematic review identified 1441 studies of which 161 were included. Management of RSV remains centered around prophylaxis with the monoclonal antibody palivizumab, which has proven effective in reducing RSV hospitalization (RSVH) in preterm infants half-life are currently entering phase 3 trials. There are approximately 15 RSV vaccines in clinical development targeting the infant directly or indirectly via the mother. Palivizumab remains the only product licensed for RSV prophylaxis, and only available for high-risk infants. For the general population, there are several promising vaccines and monoclonal antibodies in various stages of clinical development, with the aim to significantly reduce the global healthcare impact of this common viral infection. AbbVie.

  8. Prevalence and clinical features of respiratory syncytial virus in children hospitalized for community-acquired pneumonia in northern Brazil

    Directory of Open Access Journals (Sweden)

    Lamarão Letícia

    2012-05-01

    Full Text Available Abstract Background Childhood pneumonia and bronchiolitis is a leading cause of illness and death in young children worldwide with Respiratory Syncytial Virus (RSV as the main viral cause. RSV has been associated with annual respiratory disease outbreaks and bacterial co-infection has also been reported. This study is the first RSV epidemiological study in young children hospitalized with community-acquired pneumonia (CAP in Belém city, Pará (Northern Brazil. Methods With the objective of determining the prevalence of RSV infection and evaluating the patients’ clinical and epidemiological features, we conducted a prospective study across eight hospitals from November 2006 to October 2007. In this study, 1,050 nasopharyngeal aspirate samples were obtained from hospitalized children up to the age of three years with CAP, and tested for RSV antigen by direct immunofluorescence assay and by Reverse Transcription Polymerase Chain Reaction (RT-PCR for RSV Group identification. Results RSV infection was detected in 243 (23.1% children. The mean age of the RSV-positive group was lower than the RSV-negative group (12.1 months vs 15.5 months, pppppp Conclusion The present study highlights the relevance of RSV infection in hospitalized cases of CAP in our region; our findings warrant the conduct of further investigations which can help design strategies for controlling the disease.

  9. Molecular characteristics and successful management of a respiratory syncytial virus outbreak among pediatric patients with hemato-oncological disease

    Directory of Open Access Journals (Sweden)

    Claas Baier

    2018-02-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is responsible for upper and lower respiratory tract infection in adults and children. Especially immunocompromised patients are at high risk for a severe course of infection, and mortality is increased. Moreover RSV can spread in healthcare settings and can cause outbreaks. Herein we demonstrate the successful control and characteristics of a RSV outbreak that included 8 patients in our Department of Pediatric Hematology and Oncology. Methods We performed an epidemiologic investigation and a molecular analysis of the outbreak strains. Moreover we present the outbreak control bundle and our concept for RSV screening in the winter season. Results RSV A and B strains caused the outbreak. RSV B strains affected 3 patients, 2 of whom were co-infected with RSV A. Exactly this RSV A strain was detected in another 5 patients. Our multimodal infection control bundle including prophylactic RSV screening was able to rapidly stop the outbreak. Conclusion An infection control bundle in RSV outbreaks should address all potential transmission pathways. In pediatric settings the restriction of social activities might have a temporal negative impact on quality of life but helps to limit transmission opportunities. Molecular analysis allows better understanding of RSV outbreaks and, if done in a timely manner, might be helpful for guidance of infection control measures.

  10. The impact of severe respiratory syncytial virus on the child, caregiver, and family during hospitalization and recovery.

    Science.gov (United States)

    Leidy, Nancy Kline; Margolis, Mary Kay; Marcin, James P; Flynn, Jennifer A; Frankel, Lorry R; Johnson, Susan; Langkamp, Diane; Simoes, Eric A F

    2005-06-01

    To quantify the magnitude of child, caregiver, and family distress associated with hospitalization for severe respiratory syncytial virus (RSV) and the posthospitalization recovery period. A prospective study of 46 RSV-hospitalized infants and children family health and functioning (Family Adaptability and Cohesion Evaluation Scale II) were recorded. The mean age of the sample was 10.2 months; 51% of the subjects were male. The average duration of hospital stay for the RSV group was 5.8 +/- 8 days. Most patients received supplemental oxygen (76%) and were monitored for apnea (60%). The mean age of the caregivers (93% mothers) was 29 years. During hospitalization, the RSV-infected patients' health and functional status were significantly poorer than those of control subjects. Caregivers of RSV-infected children reported more stress, greater anxiety, poorer health, and poorer family health and functioning. As long as 60 days after discharge, caregivers of RSV-infected children reported the children's health as significantly poorer and were personally more anxious, compared with control subjects. RSV-related hospitalization creates significant distress for infants and children, caregivers, and families, with some effects extending as long as 60 days after discharge.

  11. Inhibition of priming for bovine respiratory syncytial virus-specific protective immune responses following parenteral vaccination of passively immune calves.

    Science.gov (United States)

    Ellis, John; Gow, Sheryl; Bolton, Michael; Burdett, William; Nordstrom, Scott

    2014-12-01

    The effect of maternal antibodies (MatAb) on immunological priming by neonatal parenteral vaccination for bovine respiratory syncytial virus (BRSV) was addressed for the first time in experimental infection in 34 Holstein calves. Both vaccinated and control calves developed moderate to severe respiratory disease characteristic of acute BRSV infection. There were no differences in clinical signs, BRSV shed, arterial oxygen concentrations, or mortality between vaccinated and control calves after BRSV challenge approximately 11 wk after vaccination. There were no anamnestic antibody or cytokine responses in the vaccinates after challenge. Lung lesions were extensive in both groups, and although there was a statistically significant (P = 0.05) difference between groups, this difference was considered not biologically significant. These data indicate that stimulation of protective immune responses was inhibited by maternal antibodies when a combination modified-live BRSV vaccine was administered parenterally to young passively immune calves. Alternate routes of administration or different vaccine formulations should be used to successfully immunize young calves with good passive antibody transfer.

  12. [Clinical and epidemiological differences between Bordetella pertussis and respiratory syncytial virus infections in infants: a matched case control study].

    Science.gov (United States)

    Giménez-Sánchez, Francisco; Cobos-Carrascosa, Elena; Sánchez-Forte, Miguel; López-Sánchez, María Ángeles; González-Jiménez, Yolanda; Azor-Martínez, Ernestina

    2014-01-01

    An increase in cases of pertussis, mainly in young infants, has been reported in the last few years. The clinical presentation of this disease is very similar to that produced by respiratory syncytial virus (RSV), which makes the diagnosis difficult. To compare the clinical and epidemiological characteristics between Bordetella pertussis and RSV infections in infants admitted to hospital. An analytical matched case-control study was conducted during the period 2008-2011. Cases were defined as infants admitted with pertussis confirmed by PCR in nasopharyngeal aspirate. Each case was matched by age, sex and date of admission to two controls defined as patients with RSV infection detected by immunochromatography in nasal aspirate. Demographic, clinical, laboratory data were compared. Seventy eight patients (26 cases of pertussis and 52 controls RSV+) were included. Sociodemographic characteristics were similar in both groups. Cases had more days of symptoms prior to admission, longer hospital stays, and increased frequency of epidemic family environment. Apnoea and cyanosis were more frequent. Cases of pertussis were more likely to have apnoea, cyanosis, and lymphocytosis while RSV infections had more frequent fever, vomiting and respiratory distress. The clinical presentations of pertussis and RSV infection are similar, but there are some characteristics that can help to distinguish between them. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

    Directory of Open Access Journals (Sweden)

    Tzeng-Jih Lin

    2013-12-01

    Full Text Available Human respiratory syncytial virus (HRSV infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata is a common ingredient of Ge-Gen-Tang (Kakkon-to and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to, which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2 and lower (A549 respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001 against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001 by inhibiting viral attachment (p < 0.0001 and penetration (p < 0.0001. However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

  14. Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru.

    Directory of Open Access Journals (Sweden)

    Andrew Wu

    Full Text Available The disease burden and risk factors for respiratory syncytial virus (RSV and human metapneumovirus (MPV infections among children living in remote, rural areas remain unclear.We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI, including lower respiratory tract infection (LRTI, were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression.Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05 among children with RSV (clinic 41% and hospital 5.3% and MPV ARI (38% and 3.5% when compared with other viral infections (23% and 0.7% and infections without virus detected (24% and 0.6%. In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03, the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38, residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents. Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01.In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses

  15. Detection of antibodies and risk factors for infection with bovine respiratory syncytial virus and parainfluenza virus 3 in dual-purpose farms in Colima, Mexico.

    Science.gov (United States)

    Figueroa-Chávez, Daniel; Segura-Correa, José C; García-Márquez, Luís Jorge; Pescador-Rubio, Alfonso; Valdivia-Flores, Arturo Gerardo

    2012-10-01

    A cross-sectional study was carried out, from November 2007 to March 2008, to estimate the prevalence of and to determine risk factors associated with bovine syncytial respiratory virus (BRSV) and parainfluenza 3 virus (PIV3) in dual-purpose herds in Colima, México. One hundred and seventy-six sera from 33 herds for PIV3 and 232 sera from 44 herds for BRSV were used. Sera were analyzed by indirect ELISA for the detection of antibodies against BRSV and PIV3 in cattle herds to determine the seroprevalence of respiratory diseases. The apparent and true prevalences for PIV3 were 60.8% and 54.4% and for BRSV 52.2% and 50.8%, respectively. The percentage of herds showing at least one positive animal was 78.7% for PIV3, and 93.2% for BRSV. Age (≤ 12, 13-48, and >48 months old) and respiratory signs (no, yes) showed significant association (P < 0.05) with PIV3 and age with BRSV. This study showed that animals were exposed to both viruses and that age was the main risk factor. The need to establish new vaccination plans to effectively protect cattle against those infections in the state of Colima, Mexico is suggested.

  16. Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.

    Science.gov (United States)

    Munday, Diane C; Howell, Gareth; Barr, John N; Hiscox, Julian A

    2015-03-01

    The aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (HRSV), a major cause of paediatric illness. Quantitative proteomics, underpinned by stable isotope labelling with amino acids in cell culture, coupled to LC-MS/MS, was applied to mitochondrial fractions prepared from HRSV-infected and mock-infected cells 12 and 24 h post-infection. Datasets were analysed using ingenuity pathway analysis, and the results were validated and characterised using bioimaging, targeted inhibition and gene depletion. The data quantitatively indicated that antiviral signalling proteins converged on mitochondria during HRSV infection. The mitochondrial receptor protein Tom70 was found to act in an antiviral manner, while its chaperone, Hsp90, was confirmed to be a positive viral factor. Proteins associated with different organelles were also co-enriched in the mitochondrial fractions from HRSV-infected cells, suggesting that alterations in organelle dynamics and membrane associations occur during virus infection. Protein and pathway-specific alterations occur to the mitochondrial proteome in a spatial and temporal manner during HRSV infection, suggesting that this organelle may have altered functions. These could be targeted as part of potential therapeutic strategies to disrupt virus biology. © 2014 Royal Pharmaceutical Society.

  17. Respiratory Syncytial Virus Infections in Infants: Detel1ninants of Clinical Severity

    NARCIS (Netherlands)

    A.H. Brandenburg (Afke)

    2000-01-01

    textabstractIn 1955 a virus was isolated by Morris et al. from a chimpanzee with an upper respiratory tract infection. This apparently new virus was originally called chimpanzee coryza agent. Soon aftclwards, when it was isolated from children with respiratory disease, it became clear that this

  18. Risk of nosocomial respiratory syncytial virus infection and effectiveness of control measures to prevent transmission events: a systematic review.

    Science.gov (United States)

    French, Clare E; McKenzie, Bruce C; Coope, Caroline; Rajanaidu, Subhadra; Paranthaman, Karthik; Pebody, Richard; Nguyen-Van-Tam, Jonathan S; Higgins, Julian P T; Beck, Charles R

    2016-07-01

    Respiratory syncytial virus (RSV) causes a significant public health burden, and outbreaks among vulnerable patients in hospital settings are of particular concern. We reviewed published and unpublished literature from hospital settings to assess: (i) nosocomial RSV transmission risk (attack rate) during outbreaks, (ii) effectiveness of infection control measures. We searched the following databases: MEDLINE, EMBASE, CINAHL, Cochrane Library, together with key websites, journals and grey literature, to end of 2012. Risk of bias was assessed using the Cochrane risk of bias tool or Newcastle-Ottawa scale. A narrative synthesis was conducted. Forty studies were included (19 addressing research question one, 21 addressing question two). RSV transmission risk varied by hospital setting; 6-56% (median: 28·5%) in neonatal/paediatric settings (n = 14), 6-12% (median: 7%) in adult haematology and transplant units (n = 3), and 30-32% in other adult settings (n = 2). For question two, most studies (n = 13) employed multi-component interventions (e.g. cohort nursing, personal protective equipment (PPE), isolation), and these were largely reported to be effective in reducing nosocomial transmission. Four studies examined staff PPE; eye protection appeared more effective than gowns and masks. One study reported on RSV prophylaxis for patients (RSV-Ig/palivizumab); there was no statistical evidence of effectiveness although the sample size was small. Overall, risk of bias for included studies tended to be high. We conclude that RSV transmission risk varies widely during hospital outbreaks. Although multi-component control strategies appear broadly successful, further research is required to disaggregate the effectiveness of individual components including the potential role of palivizumab prophylaxis. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  19. Genetic Variability of Group A Human Respiratory Syncytial Virus Strains Circulating in Germany from 1998 to 2007▿ †

    Science.gov (United States)

    Reiche, Janine; Schweiger, Brunhilde

    2009-01-01

    The variability between respiratory syncytial virus (RSV) strains is one of the features of RSV infections that might contribute to the ability of the virus to infect people repeatedly and cause yearly outbreaks. To study the molecular epidemiology of RSV, more than 1,400 RSV isolates from human nasopharyngeal aspirates or nasal or throat swabs from patients with respiratory illness were identified and differentiated by TaqMan reverse transcription-PCR into groups A and B. RSV group A was dominant in seven out of nine epidemic seasons. Phylogenetic analysis revealed that RSV group A genotypes GA2 and GA5 circulated from 1998 to 2007. Genotype GA7 was present in only two seasons (1999 to 2000 and 2002 to 2003). Comparison of the synonymous mutation/nonsynonymous mutation ratios showed greater evidence for selection pressure for genotype GA2 (1.18) than for GA5 (4.34). Partial protein sequences were predicted to encode G proteins of 298 amino acids in length and in a few cases of G proteins of 297 amino acids in length. Amino acid analysis also revealed genotype-specific amino acid substitutions: two substitutions for genotype GA2, seven for GA5, and three for GA7. Two to four putative, genotype-specific N-linked glycosylation sites were determined. Predicted O-glycosylation sites included 22 to 34 residues. This study provides for the first time data on the circulation pattern of RSV group A genotypes and their molecular characterization in Germany during nine consecutive epidemic seasons. PMID:19386848

  20. Whole genome sequencing and evolutionary analysis of human respiratory syncytial virus A and B from Milwaukee, WI 1998-2010.

    Directory of Open Access Journals (Sweden)

    Cecilia Rebuffo-Scheer

    Full Text Available BACKGROUND: Respiratory Syncytial Virus (RSV is the leading cause of lower respiratory-tract infections in infants and young children worldwide. Despite this, only six complete genome sequences of original strains have been previously published, the most recent of which dates back 35 and 26 years for RSV group A and group B respectively. METHODOLOGY/PRINCIPAL FINDINGS: We present a semi-automated sequencing method allowing for the sequencing of four RSV whole genomes simultaneously. We were able to sequence the complete coding sequences of 13 RSV A and 4 RSV B strains from Milwaukee collected from 1998-2010. Another 12 RSV A and 5 RSV B strains sequenced in this study cover the majority of the genome. All RSV A and RSV B sequences were analyzed by neighbor-joining, maximum parsimony and Bayesian phylogeny methods. Genetic diversity was high among RSV A viruses in Milwaukee including the circulation of multiple genotypes (GA1, GA2, GA5, GA7 with GA2 persisting throughout the 13 years of the study. However, RSV B genomes showed little variation with all belonging to the BA genotype. For RSV A, the same evolutionary patterns and clades were seen consistently across the whole genome including all intergenic, coding, and non-coding regions sequences. CONCLUSIONS/SIGNIFICANCE: The sequencing strategy presented in this work allows for RSV A and B genomes to be sequenced simultaneously in two working days and with a low cost. We have significantly increased the amount of genomic data that is available for both RSV A and B, providing the basic molecular characteristics of RSV strains circulating in Milwaukee over the last 13 years. This information can be used for comparative analysis with strains circulating in other communities around the world which should also help with the development of new strategies for control of RSV, specifically vaccine development and improvement of RSV diagnostics.

  1. One-step multiplex real time RT-PCR for the detection of bovine respiratory syncytial virus, bovine herpesvirus 1 and bovine parainfluenza virus 3

    Directory of Open Access Journals (Sweden)

    Thonur Leenadevi

    2012-03-01

    Full Text Available Abstract Background Detection of respiratory viruses in veterinary species has traditionally relied on virus detection by isolation or immunofluorescence and/or detection of circulating antibody using ELISA or serum neutralising antibody tests. Multiplex real time PCR is increasingly used to diagnose respiratory viruses in humans and has proved to be superior to traditional methods. Bovine respiratory disease (BRD is one of the most common causes of morbidity and mortality in housed cattle and virus infections can play a major role. We describe here a one step multiplex reverse transcriptase quantitative polymerase chain reaction (mRT-qPCR to detect the viruses commonly implicated in BRD. Results A mRT-qPCR assay was developed and optimised for the simultaneous detection of bovine respiratory syncytial virus (BRSV, bovine herpes virus type 1 (BoHV-1 and bovine parainfluenza virus type 3 (BPI3 i & ii nucleic acids in clinical samples from cattle. The assay targets the highly conserved glycoprotein B gene of BoHV-1, nucleocapsid gene of BRSV and nucleoprotein gene of BPI3. This mRT-qPCR assay was assessed for sensitivity, specificity and repeatability using in vitro transcribed RNA and recent field isolates. For clinical validation, 541 samples from clinically affected animals were tested and mRT-qPCR result compared to those obtained by conventional testing using virus isolation (VI and/or indirect fluorescent antibody test (IFAT. Conclusions The mRT-qPCR assay was rapid, highly repeatable, specific and had a sensitivity of 97% in detecting 102 copies of BRSV, BoHV-1 and BPI3 i & ii. This is the first mRT-qPCR developed to detect the three primary viral agents of BRD and the first multiplex designed using locked nucleic acid (LNA, minor groove binding (MGB and TaqMan probes in one reaction mix. This test was more sensitive than both VI and IFAT and can replace the aforesaid methods for virus detection during outbreaks of BRD.

  2. Chimeric Bovine Respiratory Syncytial Virus with Attachment and Fusion Glycoproteins Replaced by Bovine Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase and Fusion Proteins

    Science.gov (United States)

    Stope, Matthias B.; Karger, Axel; Schmidt, Ulrike; Buchholz, Ursula J.

    2001-01-01

    Chimeric bovine respiratory syncytial viruses (BRSV) expressing glycoproteins of bovine parainfluenza virus type 3 (BPIV-3) instead of BRSV glycoproteins were generated from cDNA. In the BRSV antigenome cDNA, the open reading frames of the major BRSV glycoproteins, attachment protein G and fusion protein F, were replaced individually or together by those of the BPIV-3 hemagglutinin-neuraminidase (HN) and/or fusion (F) glycoproteins. Recombinant virus could not be recovered from cDNA when the BRSV F open reading frame was replaced by the BPIV-3 F open reading frame. However, cDNA recovery of the chimeric virus rBRSV-HNF, with both glycoproteins replaced simultaneously, and of the chimeric virus rBRSV-HN, with the BRSV G protein replaced by BPIV-3 HN, was successful. The replication rates of both chimeras were similar to that of standard rBRSV. Moreover, rBRSV-HNF was neutralized by antibodies specific for BPIV-3, but not by antibodies specific to BRSV, demonstrating that the BRSV glycoproteins can be functionally replaced by BPIV-3 glycoproteins. In contrast, rBRSV-HN was neutralized by BRSV-specific antisera, but not by BPIV-3 specific sera, showing that infection of rBRSV-HN is mediated by BRSV F. Hemadsorption of cells infected with rBRSV-HNF and rBRSV-HN proved that BPIV-3 HN protein expressed by rBRSV is functional. Colocalization of the BPIV-3 glycoproteins with BRSV M protein was demonstrated by confocal laser scan microscopy. Moreover, protein analysis revealed that the BPIV-3 glycoproteins were present in chimeric virions. Taken together, these data indicate that the heterologous glycoproteins were not only expressed but were incorporated into the envelope of recombinant BRSV. Thus, the envelope glycoproteins derived from a member of the Respirovirus genus can together functionally replace their homologs in a Pneumovirus background. PMID:11533200

  3. The relationship between antibody status to bovine corona virus and bovine respiratory syncytial virus and disease incidence, reproduction and herd characteristics in dairy herds

    Directory of Open Access Journals (Sweden)

    Tråvén Madeleine

    2010-06-01

    Full Text Available Abstract Background Bovine respiratory syncytial virus (BRSV and bovine corona virus (BCV affects cattle worldwide. Our objective was to evaluate the effects of these infections on general health and reproduction parameters measurable on herd level and to explore the association between antibody status and some herd characteristics. Methods We collected a pooled milk sample from five primiparous cows from 79 Swedish dairy herds in September 2006. The samples were analysed for immunoglobulin G antibodies to BCV and BRSV with indirect enzyme-linked immunosorbent assays. Herd level data from 1 September 2005 to 30 August 2006 were accessed retrospectively. The location of the herds was mapped using a geographical information system. Results Ten herds were antibody negative to both viruses and were compared with 69 herds positive to BCV or BRSV or both. Positive herds had a higher (P = 0.001 bulk tank milk somatic cell count (BMSCC compared with negative herds. The medians for all other analyzed health and reproductive parameters were consistently in favour of the herds negative to both viruses although the differences were not statistically significant. A higher proportion (P = 0.01 of herds used professional technicians for artificial insemination, rather than farm personnel, amongst the 33 herds negative to BCV compared with the 46 positive herds. Conclusions Our result shows that herds that were antibody positive to BCV and/or BRSV had a higher BMSCC compared with herds negative to BCV and BRSV. There was also tendency that negative herds had a better general herd health compared with positive. A higher proportion amongst the BCV negative herds used external technicians for AI instead of farm personnel, indicating that it is possible to avoid infection although having regular visits. Negative herds were located in close proximity to positive herds, indicating that local spread and airborne transmission between herds might not be of great

  4. Evidence that maturation of the N-linked glycans of the respiratory syncytial virus (RSV) glycoproteins is required for virus-mediated cell fusion: The effect of α-mannosidase inhibitors on RSV infectivity

    International Nuclear Information System (INIS)

    McDonald, Terence P.; Jeffree, Chris E.; Li, Ping; Rixon, Helen W. McL.; Brown, Gaie; Aitken, James D.; MacLellan, Kirsty; Sugrue, Richard J.

    2006-01-01

    Glycan heterogeneity of the respiratory syncytial virus (RSV) fusion (F) protein was demonstrated by proteomics. The effect of maturation of the virus glycoproteins-associated glycans on virus infectivity was therefore examined using the α-mannosidase inhibitors deoxymannojirimycin (DMJ) and swainsonine (SW). In the presence of SW the N-linked glycans on the F protein appeared in a partially mature form, whereas in the presence of DMJ no maturation of the glycans was observed. Neither inhibitor had a significant effect on G protein processing or on the formation of progeny virus. Although the level of infectious virus and syncytia formation was not significantly affected by SW-treatment, DMJ-treatment correlated with a one hundred-fold reduction in virus infectivity. Our data suggest that glycan maturation of the RSV glycoproteins, in particular those on the F protein, is an important step in virus maturation and is required for virus infectivity

  5. Recombinant subgroup B human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats.

    Science.gov (United States)

    Lemon, Ken; Nguyen, D Tien; Ludlow, Martin; Rennick, Linda J; Yüksel, Selma; van Amerongen, Geert; McQuaid, Stephen; Rima, Bert K; de Swart, Rik L; Duprex, W Paul

    2015-03-01

    Human respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro and in vivo models of HRSV focus almost exclusively on subgroup A viruses. Here, a recombinant (r) subgroup B virus (rHRSV(B05)) was generated based on a consensus genome sequence obtained directly from an unpassaged clinical specimen from a hospitalized infant. An additional transcription unit containing the gene encoding enhanced green fluorescent protein (EGFP) was introduced between the phosphoprotein and matrix genes (position 5) of the genome to generate rHRSV(B05)EGFP(5). The recombinant viruses replicated efficiently in both HEp-2 cells and in well-differentiated normal human bronchial cells grown at air-liquid interface. Intranasal infection of cotton rats (Sigmodon hispidus) resulted in high numbers of EGFP(+) cells in epithelia of the nasal septum and conchae. When administered in a relatively large inoculum volume, the virus also replicated efficiently in bronchiolar epithelial cells and spread extensively in both the upper and lower respiratory tracts. Virus replication was not observed in ciliated epithelial cells of the trachea. This is the first virulent rHRSV strain with the genetic composition of a currently circulating wild-type virus. In vivo tracking of infected cells by means of EGFP fluorescence in the absence of cytopathic changes increases the sensitivity of virus detection in HRSV pathogenesis studies. Virology as a discipline has depended on monitoring cytopathic effects following virus culture in vitro. However, wild-type viruses isolated from patients often do not cause significant changes to infected cells, necessitating blind passage. This can lead to genetic and phenotypic changes and the generation of high-titer, laboratory-adapted viruses with

  6. Detection of antibodies and risk factors for infection with bovine respiratory syncytial virus and parainfluenza virus-3 in beef cattle of Yucatan, Mexico.

    Science.gov (United States)

    Solís-Calderón, J J; Segura-Correa, J C; Aguilar-Romero, F; Segura-Correa, V M

    2007-11-15

    We collected blood samples from 756 > or =2-year-old cattle in 54 herds in Yucatan, Mexico, and used all of those to determine the antibody seroprevalences (in an indirect enzyme-linked inmunosorbance assay) to bovine respiratory syncytial virus (BRSV) and risk factors for animal-level seropositivity. We used 728 of the same samples (from 52 of the same herds) to do the same for parainfluenza virus-3 (PIV3). Cattle were selected by two-stage cluster sampling. Herd-level and animal-level risk factors were obtained through a personal interview. We analyzed the data by using a random-effects multivariable logistic regression model for clustered observations. All herds had at least 3 (BRSV) or 5 (PIV3) seropositive animals. The animal-level true seroprevalences were: 90.8% (86.5, 95.2%) and 85.6% (80.9, 90.4%) for BRSV and PIV3, respectively. Animals in large herds and old animals had the highest odds of being seropositives to BRSV, and those risk factors plus animals born on the farm for PIV3 infection.

  7. Diagnosis of enzootic pneumonia in Danish cattle: reverse transcription-polymerase chain reaction assay for detection of bovine respiratory syncytial virus in naturally and experimentally infected cattle

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tjørnehøj, Kirsten; Viuff, B.

    1999-01-01

    A reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for detection of bovine respiratory syncytial virus (BRSV) in lung tissue of naturally and experimentally infected cattle. Primers were selected from the gene coding the F fusion protein, which is relatively conserved...... among BRSV isolates. The RT-PCR assay was highly specific, it yielded positive reactions only when performed on BRSV-infected cell cultures or tissues. The detection limit of the RT-PCR assay was assessed as 5 TCID50. BRSV was detected in tissues of the respiratory tract and in the tracheobroncheal...

  8. Burden of influenza, respiratory syncytial virus, and other respiratory viruses and the completeness of respiratory viral identification among respiratory inpatients, Canada, 2003-2014.

    Science.gov (United States)

    Schanzer, Dena L; Saboui, Myriam; Lee, Liza; Nwosu, Andrea; Bancej, Christina

    2018-01-01

    A regression-based study design has commonly been used to estimate the influenza burden; however, these estimates are not timely and many countries lack sufficient virological data. Alternative approaches that would permit a timelier assessment of the burden, including a sentinel surveillance approach recommended by the World Health Organization (WHO), have been proposed. We aimed to estimate the hospitalization burden attributable to influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) and to assess both the completeness of viral identification among respiratory inpatients in Canada and the implications of adopting other approaches. Respiratory inpatient records were extracted from the Canadian Discharge Abstract Database from 2003 to 2014. A regression model was used to estimate excess respiratory hospitalizations attributable to influenza, RSV, and ORV by age group and diagnostic category and compare these estimates with the number with a respiratory viral identification. An estimated 33 (95% CI: 29, 38), 27 (95% CI: 22, 33), and 27 (95% CI: 18, 36) hospitalizations per 100 000 population per year were attributed to influenza, RSV, and ORV, respectively. An influenza virus was identified in an estimated 78% (95% CI: 75, 81) and 17% (95% CI: 15, 21) of respiratory hospitalizations attributed to influenza for children and adults, respectively, and 75% of influenza-attributed hospitalizations had an ARI diagnosis. Hospitalization rates with respiratory viral identification still underestimate the burden. Approaches based on acute respiratory case definitions will likely underestimate the burden as well, although each proposed method should be compared with regression-based estimates of influenza-attributed burden as a way of assessing their validity. © 2017 The Authors. Influenza and Other Respiratory Viruses. Published by John Wiley & Sons Ltd.

  9. Epidemiology and Molecular Characterization of Human Respiratory Syncytial Virus in Senegal after Four Consecutive Years of Surveillance, 2012–2015

    Science.gov (United States)

    Cisse, El Hadj Abdel Kader; Kiori, Davy E.; Sarr, Fatoumata Diene; Sy, Sara; Goudiaby, Debora; Richard, Vincent; Niang, Mbayame Ndiaye

    2016-01-01

    Background The burden of respiratory syncytial virus (RSV) infection remains poorly defined in Africa. To address this, we carried out a descriptive and retrospective pilot study, with a focus on the epidemiology of RSV in Senegal after 4 years of surveillance. Methodology and Results From January 2012 to October 2015 swabs were collected from consenting ILI outpatients. Viral detection was performed using RV16 kit enabling direct subtyping of RSV-A and B. For the molecular characterization of HRSV, the second hypervariable region of the Glycoprotein (G) gene was targeted for sequencing. We enrolled 5338 patients with 2803 children younger than five years of age (52.5%). 610 (11.4%) were positive for RSV infection: 276 (45.2%) were group A infections, 334 (54.8%) were group B infections and 21 (3.4%) were A/B co-infections. RSV detection rate is significantly higher (P Senegal clustered with strains that were previously assigned NA1 and novel ON1 genotype sequences. RSV-B sequences from Senegal clustered with the BA9 genotype. At the amino acid level, RSV-A strains from Senegal show proximity with the genotype ON1 characterized by a 72 nt insertion in G, resulting in 24 extra amino acids of which 23 are duplications of aa 261–283. Conclusion Globally our results show a clear circulation pattern of RSV in the second half of each year, between June and September and possibly extending into November, with children under 5 being more susceptible. Molecular studies identified the novel strains ON1 and BA9 as the major genotypes circulating in Senegal between 2012 and 2015. PMID:27315120

  10. Epidemiology and Molecular Characterization of Human Respiratory Syncytial Virus in Senegal after Four Consecutive Years of Surveillance, 2012-2015.

    Science.gov (United States)

    Fall, Amary; Dia, Ndongo; Cisse, El Hadj Abdel Kader; Kiori, Davy E; Sarr, Fatoumata Diene; Sy, Sara; Goudiaby, Debora; Richard, Vincent; Niang, Mbayame Ndiaye

    2016-01-01

    The burden of respiratory syncytial virus (RSV) infection remains poorly defined in Africa. To address this, we carried out a descriptive and retrospective pilot study, with a focus on the epidemiology of RSV in Senegal after 4 years of surveillance. From January 2012 to October 2015 swabs were collected from consenting ILI outpatients. Viral detection was performed using RV16 kit enabling direct subtyping of RSV-A and B. For the molecular characterization of HRSV, the second hypervariable region of the Glycoprotein (G) gene was targeted for sequencing. We enrolled 5338 patients with 2803 children younger than five years of age (52.5%). 610 (11.4%) were positive for RSV infection: 276 (45.2%) were group A infections, 334 (54.8%) were group B infections and 21 (3.4%) were A/B co-infections. RSV detection rate is significantly higher (P Senegal clustered with strains that were previously assigned NA1 and novel ON1 genotype sequences. RSV-B sequences from Senegal clustered with the BA9 genotype. At the amino acid level, RSV-A strains from Senegal show proximity with the genotype ON1 characterized by a 72 nt insertion in G, resulting in 24 extra amino acids of which 23 are duplications of aa 261-283. Globally our results show a clear circulation pattern of RSV in the second half of each year, between June and September and possibly extending into November, with children under 5 being more susceptible. Molecular studies identified the novel strains ON1 and BA9 as the major genotypes circulating in Senegal between 2012 and 2015.

  11. Clinical course of community-acquired respiratory syncytial virus pneumonia in newborns hospitalized in neonatal intensive care unit.

    Science.gov (United States)

    Aydın, Banu; Zenciroğlu, Ayşegül; Dilli, Dilek; Okumuş, Nurullah; İpek, M Sah; Aydın, Mustafa; Uzunalıç, Nuran; Hakan, Nilay; Kundak, Ahmet Afşin; Dursun, Arzu; Karadağ, Nilgün; Korukluoğlu, Gülay

    2013-01-01

    Respiratory syncytial virus (RSV) is a major cause of pneumonia in infants worldwide. We aimed to evaluate the clinical course of community-acquired RSV pneumonia in newborns hospitalized in neonatal intensive care unit. All the newborns diagnosed as pneumonia were prospectively evaluated for RSV infection between November 2010 and April 2011. Fifty-four specimens of nasopharyngeal secretions were tested in parallel with the RAT and the multiplex real time polymerase chain reaction (RT- PCR). Downes' score was used to assess the disease severity in patients with pneumonia. RAT has a sensitivity of 90% and a specificity of 78.5%, as the PCR technique target assay. Four of the patients with RSV pneumonia had secundum atrial septal defect (ASD) and all of four needed mechanical ventilation support. The first day Downes' score was positively correlated with time of intravenous fluid requirement (p= 0.001, r= 0.48), total oxygen need (p= 0.000, r= 0.63), and re-enteral feeding (p= 0.001, r= 0.46). Blood pH (p= 0.031, r= 0.46) were negatively correlated with Downes' score. The second day Downes' score was higher in patients with ASD than those of without ASD (3.8 ± 2.6 vs. 2 ± 1.1, p= 0.01). The most possible risk factor for longer hospital stay was the higher second day Downes' score (p= 0.02 OR: 1.9, CI 95% (1.1-3.2). All infants were discharged from hospital in a good health. RAT is sensitive and specific in detecting RSV infections in newborns. Physicians may use Downes' score for evaluation of disease severity in infants with RSV pneumonia. In these patients, ASD has increased the disease severity.

  12. Epidemiology and risk factors for severe respiratory syncytial virus infections requiring pediatric intensive care admission in Hong Kong children.

    Science.gov (United States)

    Leung, T F; Lam, D S Y; Miu, T Y; Hon, K L; Chau, C S K; Ku, S W; Lee, R S Y; Chow, P Y; Chiu, W K; Ng, D K K

    2014-04-01

    Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in young children. However, there are limited data on severe RSV infection requiring pediatric intensive care unit (PICU) admission. This retrospective study described features of RSV-associated PICU admissions in Hong Kong and investigated factors for mortality and duration of PICU stay. Children with laboratory-confirmed RSV infection and admitted to the PICUs of all eight government hospitals in Hong Kong between January 2009 and June 2011 were identified from computerized auditing systems and PICU databases. RSV in respiratory samples was detected by direct immunofluorescence and/or viral culture. The relationships between mortality and PICU duration and demographic and clinical factors were analyzed. A total of 118 (2.4 %) PICU admissions were identified among 4,912 RSV-positive pediatric cases in all hospitals. Sixty-five (55.6 %) patients were infants. PICU admissions were higher between October and March. Eight (6.8 %) patients died, but only two were infants. RSV-associated mortality was related to prior sick contact, presence of older siblings, neurodevelopmental conditions, chromosomal and genetic diseases, and bacterial co-infections, but none was significant following logistic regression analyses (odds ratio 9.36, 95 % confidence interval 0.91-96.03 for prior sick contact, p = 0.060). Chronic lung disease was the only risk factor for the duration of PICU admission (β = 0.218, p = 0.017). The majority of RSV-infected children do not require PICU support. There is winter seasonality for RSV-associated PICU admission in Hong Kong. Prior sick contact is the only risk factor for RSV-associated mortality, whereas the presence of chronic lung disease is associated with longer PICU stay. The current risk-based approach of RSV prophylaxis may not be effective in reducing severe RSV infections.

  13. Respiratory syncytial virus: a systematic scientometric analysis of the global publication output and the gender distribution of publishing authors.

    Science.gov (United States)

    Brüggmann, Dörthe; Köster, Corinna; Klingelhöfer, Doris; Bauer, Jan; Ohlendorf, Daniela; Bundschuh, Matthias; Groneberg, David A

    2017-07-26

    Worldwide, the respiratory syncytial virus (RSV) represents the predominant viral agent causing bronchiolitis and pneumonia in children. To conduct research and tackle existing healthcare disparities, RSV-related research activities around the globe need to be described. Hence, we assessed the associated scientific output (represented by research articles) by geographical, chronological and socioeconomic criteria and analysed the authors publishing in the field by gender. Also, the 15 most cited articles and the most prolific journals were identified for RSV research. Retrospective, descriptive study. The NewQIS (New Quality and Quantity Indices in Science) platform was employed to identify RSV-related articles published in the Web of Science until 2013. We performed a numerical analysis of all articles, and examined citation-based aspects (eg, citation rates); results were visualised by density equalising mapping tools. We identified 4600 RSV-related articles. The USA led the field; US-American authors published 2139 articles (46.5%% of all identified articles), which have been cited 83 000 times. When output was related to socioeconomic benchmarks such as gross domestic product or Research and Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in leading positions. A total of 614 articles on RSV (13.34% of all articles) were attributed to scientific collaborations. These were primarily established between high-income countries. The gender analysis indicated that male scientists dominated in all countries except Brazil. The majority of RSV-related research articles originated from high-income countries whereas developing nations showed only minimal publication productivity and were barely part of any collaborative networks. Hence, research capacity in these nations should be increased in order to assist in addressing inequities in resource allocation and the clinical burden of RSV in these countries. © Article author(s) (or their employer

  14. Reversion of somatic mutations of the respiratory syncytial virus-specific human monoclonal antibody Fab19 reveal a direct relationship between association rate and neutralizing potency.

    Science.gov (United States)

    Bates, John T; Keefer, Christopher J; Utley, Thomas J; Correia, Bruno E; Schief, William R; Crowe, James E

    2013-04-01

    The role of affinity in determining neutralizing potency of mAbs directed against viruses is not well understood. We investigated the kinetic, structural, and functional advantage conferred by individual naturally occurring somatic mutations in the Ab H chain V region of Fab19, a well-described neutralizing human mAb directed to respiratory syncytial virus. Comparison of the affinity-matured Ab Fab19 with recombinant Fab19 Abs that were variants containing reverted amino acids from the inferred unmutated ancestor sequence revealed the molecular basis for affinity maturation of this Ab. Enhanced binding was achieved through mutations in the third H chain CDR (HCDR3) that conferred a markedly faster on-rate and a desirable increase in antiviral neutralizing activity. In contrast, most somatic mutations in the HCDR1 and HCDR2 regions did not significantly enhance Ag binding or antiviral activity. We observed a direct relationship between the measured association rate (Kon) for F protein and antiviral activity. Modeling studies of the structure of the Ag-Ab complex suggested the HCDR3 loop interacts with the antigenic site A surface loop of the respiratory syncytial virus F protein, previously shown to contain the epitope for this Ab by experimentation. These studies define a direct relationship of affinity and neutralizing activity for a viral glycoprotein-specific human mAb.

  15. Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

    Science.gov (United States)

    Kashiwagi, Tomoko; Okada, Yukiko; Nomoto, Ken

    2018-02-01

    The aim of this study was to assess the safety and effectiveness of palivizumab for the prevention of lower respiratory tract infection (LRI) caused by respiratory syncytial virus (RSV) in children with immunocompromised conditions or Down syndrome. In this multicenter, post-marketing surveillance study (December 2013 to December 2015), children aged ≤24 months with immunocompromised conditions or Down syndrome (without hemodynamically significant congenital heart disease) receiving palivizumab immunoprophylaxis during two RSV seasons were observed until 30 days after the final palivizumab injection. Safety [adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), serious ADRs (SADRs)] and effectiveness (frequency, incidence, and duration of hospitalization due to RSV infections) were assessed. Of 304 patients receiving palivizumab, 167 (54.9%) had immunocompromised conditions, and 138 (45.4%) had Down syndrome; 260 (85.5%) completed palivizumab immunoprophylaxis. The annual mean (±standard deviation) number of doses was 5.3 (±2.4) per season. Overall, 220 AEs occurred in 99 patients (32.6%), including 89 SAEs in 53 patients (17.4%). Of these, 33 AEs in 25 patients (8.22%) were considered ADRs, and 13 ADRs in 11 patients (3.62%) were considered SADRs. In four patients, five SADRs (nephroblastoma and asthma in the same patient, septic shock, device-related infection, and drug-induced liver injury) were previously unreported; however, none were considered drug-related. During the observation period, five RSV infections occurred and two patients required hospitalization. Palivizumab was generally safe and effective for the prevention of LRI caused by RSV in newborns, infants, and children with immunocompromised conditions or Down syndrome up to the age of 24 months.

  16. Risk factors for admission and the role of respiratory syncytial virus ...

    African Journals Online (AJOL)

    Secretions were tested with monoclonal antibodies for RSV and pooled respiratory viruses; shell vial cultures were also established. Permission was requested from parents of RSV-infected subjects for blood draws for specific cytotoxic T-cell assays and CD4/CD8 cells on admission and repeat CTL on day 7. Results.

  17. Fc gamma receptors in respiratory syncytial virus infections: implications for innate immunity

    NARCIS (Netherlands)

    Jans, J.; Vissers, M.E.P.; Heldens, J.G.; Jonge, M.I. de; Levy, O.; Ferwerda, G.

    2014-01-01

    RSV infections are a major burden in infants less than 3 months of age. Newborns and infants express a distinct immune system that is largely dependent on innate immunity and passive immunity from maternal antibodies. Antibodies can regulate immune responses against viruses through interaction with

  18. Respiratory syncytial virus (RSV bronchiolitis: comparative study of RSV groups A and B infected children

    Directory of Open Access Journals (Sweden)

    Selir M. Straliotto

    1994-03-01

    Full Text Available The grouping characteristics of 29 respiratory syncitial virus (RSV present in nasopharyngeal cells collectedfrom hospitalized children with bronchiolitis during the 1990RSVseason in Porto Alegre, RS, were analysed. Twenty-two were grouped as belonging to group A and 7 to group B. Cyanosis, oxigen therapy, cough, lenght of hospitalization and atelectasis were observed to be more frequently found within group B infected children. Other clinical signs and symptoms were similarly found in both groups.

  19. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    International Nuclear Information System (INIS)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga; Luque, Daniel; Terrón, María C.; Calder, Lesley J.; Melero, José A.

    2014-01-01

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV F occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV F , we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV F at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy

  20. Respiratory Syncytial Virus Preterm (32-36 Completed Weeks of Gestation) Risk Estimation Measure for RSV Hospitalization in Ireland: A Prospective Study.

    Science.gov (United States)

    Sheridan-Pereira, Margaret; Murphy, Joan; Sloan, Julie; Crispino, Gloria; Leahy, Anne; Corcoran, J David; Dempsey, Eugene; Elnazir, Basil; Gavin, Patrick; Sharif, Farhana; Gul, Rizwan; Satas, Salius; Murphy, John; Gormally, Siobhan; Shanaa, Issam; Waldron, David; Mc Mahon, Paul; Carson, John; Blanken, Maarten; Bont, Louis; Paes, Bosco

    2016-01-01

    In several countries, respiratory syncytial virus prophylaxis is offered to late preterm infants who are at escalated risk of respiratory syncytial virus hospitalization (RSVH). However, targeted prophylaxis should be informed by country-specific data. This study, which uniquely includes 36 weeks of gestational age (GA) infants, aims to establish the risk factors for RSVH in 32-36 weeks of GA infants in Ireland. A prospective observational study at 13 hospitals of laboratory-confirmed RSVH in nonprophylaxed 32-36 weeks of GA infants was conducted from July 2011 to February 2014. Baseline and first-year clinical data were analyzed by using SPSS software Version 22 (IBM Corp, Armonk, NY). Significant (P history of asthma (OR: 1.9; 95% CI: 1.01-3.39). Birth from 36 weeks to 36 + 6 days mitigated RSVH risk (relative risk: 0.58; 95% CI: 0.34-0.99); however, risk factors were similar to the 32-35 weeks of GA cohort. Neonatal respiratory morbidity or being Caucasian were the population-specific independent risk factors for RSVH in 32-36 weeks of GA in Ireland, whereas the other identified independent risk factors mirrored those established in previous studies.

  1. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Luque, Daniel; Terrón, María C. [Unidad de Microscopía Electrónica y Confocal, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Calder, Lesley J. [National Institute for Medical Research, MRC, Mill Hill, London NW7 1AA (United Kingdom); Melero, José A., E-mail: jmelero@isciii.es [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain)

    2014-07-15

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV{sub F} occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV{sub F}, we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV{sub F} at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy.

  2. [The most prevalent environmental risk factors in respiratory syncytial virus bronchiolitis in infants from 0 to 24 months in a seasonal study performed in two hospitals].

    Science.gov (United States)

    León-Carrillo, Beatriz; Baldris-Catafau, Judit; Jiménez-Martínez, Soledad

    2013-01-01

    Our aim is to describe the environmental aspects of children between 0 and 24 months, who arrived in the Emergency Department of the Hospital General de Cataluña and Hospital Parc Tauli (both within Barcelona province), and were diagnosed with respiratory syncytial virus bronchiolitis from November 2010 to February 2011. A cross-sectional observational study was conducted on children of both sexes, with ages from 0 to 24 months, and diagnosed with bronchiolitits respiratory syncytial virus +. Data was obtained by completing a non-validated questionnaire, with information provided by parents and the medical history. The most common features in the study were: a mean age of 3.8 months, most were males, with siblings of school age, mothers who did not smoke during pregnancy, were in a non-smoking environment in their home, and finally, less than 5 people living together in their home. The most common risk factors n order of prevalence were, having siblings of school age, male sex, and living in smoking environment. It was observed that the majority of children had risk associated factors associated, with only 8.2% of samples not presenting any risk factors. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  3. The Susceptibilities of Respiratory Syncytial Virus to Nucleolin Receptor Blocking and Antibody Neutralization are Dependent upon the Method of Virus Purification

    Directory of Open Access Journals (Sweden)

    Leanne M. Bilawchuk

    2017-08-01

    Full Text Available Respiratory Syncytial Virus (RSV that is propagated in cell culture is purified from cellular contaminants that can confound experimental results. A number of different purification methods have been described, including methods that utilize fast protein liquid chromatography (FPLC and gradient ultracentrifugation. Thus, the constituents and experimental responses of RSV stocks purified by ultracentrifugation in sucrose and by FPLC were analyzed and compared by infectivity assay, Coomassie stain, Western blot, mass spectrometry, immuno-transmission electron microscopy (TEM, and ImageStream flow cytometry. The FPLC-purified RSV had more albumin contamination, but there was less evidence of host-derived exosomes when compared to ultracentrifugation-purified RSV as detected by Western blot and mass spectrometry for the exosome markers superoxide dismutase [Cu-Zn] (SOD1 and the tetraspanin CD63. Although the purified virus stocks were equally susceptible to nucleolin-receptor blocking by the DNA aptamer AS1411, the FPLC-purified RSV was significantly less susceptible to anti-RSV polyclonal antibody neutralization; there was 69% inhibition (p = 0.02 of the sucrose ultracentrifugation-purified RSV, 38% inhibition (p = 0.03 of the unpurified RSV, but statistically ineffective neutralization in the FPLC-purified RSV (22% inhibition; p = 0.30. The amount of RSV neutralization of the purified RSV stocks was correlated with anti-RSV antibody occupancy on RSV particles observed by immuno-TEM. RSV purified by different methods alters the stock composition and morphological characteristics of virions that can lead to different experimental responses.

  4. The Heptad Repeat C Domain of the Respiratory Syncytial Virus Fusion Protein Plays a Key Role in Membrane Fusion.

    Science.gov (United States)

    Bermingham, Imogen M; Chappell, Keith J; Watterson, Daniel; Young, Paul R

    2018-02-15

    Respiratory syncytial virus (RSV) mediates host cell entry through the fusion (F) protein, which undergoes a conformational change to facilitate the merger of viral and host lipid membrane envelopes. The RSV F protein comprises a trimer of disulfide-bonded F 1 and F 2 subunits that is present on the virion surface in a metastable prefusion state. This prefusion form is readily triggered to undergo refolding to bring two heptad repeats (heptad repeat A [HRA] and HRB) into close proximity to form a six-helix bundle that stabilizes the postfusion form and provides the free energy required for membrane fusion. This process can be triggered independently of other proteins. Here, we have performed a comprehensive analysis of a third heptad repeat region, HRC (amino acids 75 to 97), an amphipathic α-helix that lies at the interface of the prefusion F trimer and is a major structural feature of the F 2 subunit. We performed alanine scanning mutagenesis from Lys-75 to Met-97 and assessed all mutations in transient cell culture for expression, proteolytic processing, cell surface localization, protein conformation, and membrane fusion. Functional characterization revealed a striking distribution of activity in which fusion-increasing mutations localized to one side of the helical face, while fusion-decreasing mutations clustered on the opposing face. Here, we propose a model in which HRC plays a stabilizing role within the globular head for the prefusion F trimer and is potentially involved in the early events of triggering, prompting fusion peptide release and transition into the postfusion state. IMPORTANCE RSV is recognized as the most important viral pathogen among pediatric populations worldwide, yet no vaccine or widely available therapeutic treatment is available. The F protein is critical for the viral replication process and is the major target for neutralizing antibodies. Recent years have seen the development of prefusion stabilized F protein-based approaches to

  5. Respiratory syncytial virus (RSV bronchiolitis: comparative study of RSV groups A and B infected children

    Directory of Open Access Journals (Sweden)

    Selir M. Straliotto

    1994-03-01

    Full Text Available The grouping characteristics of 29 respiratory syncitial virus (RSV present in nasopharyngeal cells collectedfrom hospitalized children with bronchiolitis during the 1990RSVseason in Porto Alegre, RS, were analysed. Twenty-two were grouped as belonging to group A and 7 to group B. Cyanosis, oxigen therapy, cough, lenght of hospitalization and atelectasis were observed to be more frequently found within group B infected children. Other clinical signs and symptoms were similarly found in both groups.Estudos recentes de amostras do vírus respiratório sincicial (VRS usando anticorpos monoclonais distiguiram duas variantes antigênicas, designadas como grupos A e B. Estes grupos foram estudados em 29 secreções de nasofaringe positivas para o VRS, provenientes de crianças hospitalizadas com bronquiolite durante surto de virose por VRS, em Porto Alegre, em 1990. Destas, 22 foram grupadas como pertencentes ao grupo A e 7 ao grupo B. Alguns achados clínicos como cianose, tosse, uso de oxigênio e dias de hospitalização foram mais freqüentemente observados em crianças infectadas coin o grupo B do VRS. Outros sinais e sintomas clínicos foram similarmente encontrados nos 2 grupos.

  6. Performance of a Novel Point-of-Care Molecular Assay for Detection of Influenza A and B Viruses and Respiratory Syncytial Virus (Enigma MiniLab) in Children with Acute Respiratory Infection.

    Science.gov (United States)

    Douthwaite, Sam T; Walker, Charlotte; Adams, Elisabeth J; Mak, Catherine; Vecino Ortiz, Andres; Martinez-Alier, Nuria; Goldenberg, Simon D

    2016-01-01

    The performance of the Enigma MiniLab assay for influenza A and B viruses and respiratory syncytial virus (RSV) was compared to a centralized laboratory respiratory virus panel. The positive and negative percent agreement for influenza A virus, influenza B virus, and RSV were 79.2% (95% confidence interval [95% CI], 57.8 to 92.9%) and 99.4% (95% CI, 98.4 to 99.9), 100% (95% CI, 47.8 to 100%) and 100% (95% CI, 99.3 to 100%), 98.5% (95% CI, 94.6 to 99.8%) and 94.5% (95% CI, 91.9 to 96.4%), respectively. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. CT-morphological characterization of respiratory syncytial virus (RSV) pneumonia in immune-compromised adults

    International Nuclear Information System (INIS)

    Mayer, J.L.; Kauczor, H.U.; Lehners, N.; Egerer, G.; Heussel, C.P.

    2014-01-01

    Characterization and follow-up evaluation of chest CT of RSV pneumonia in immune-compromised adults during a seasonal epidemic. Retrospective analysis of 132 chest CT examinations of 51 adult immune-compromised patients (29 m/22f, diameter 58 years) with clinical signs of pneumonia and positive RSV test in winter 2011/2012. Two experienced chest radiologists evaluated the morphology (bronchial wall thickening, tree-in-bud, nodules, halo, ground-glass opacities, consolidations, pleural fluid) of the CT scans by consensus. Pathological findings were in 86 % of the chest CT scans: Areas of ground-glass attenuation in 64 %, consolidations in 56 %, nodules in 55 % (diameter 8 mm in maximal diameter, with halo in 71 %), pleural fluid in 44 % (diameter 2 cm), tree-in-bud in 36 %, bronchial wall thickening in 27 % and more than one morphological finding in 72 %. There were no pathological CT findings in 14 % of patients with clinical symptoms of pneumonia because these patients did not undergo follow-up. Radiological progression was found in 45 % of patients and regression in 33 % in follow-up examinations. In 37 % an additional examination of the paranasal sinuses was performed and showed sinusitis in 63 % of cases. 90 % of the patients had sinusitis as well as pneumonia. In addition to RSV, a further pathogenic agent was found in bronchoalveolar lavage of five patients (Aspergillus spec., herpes simplex virus, Pseudomonas aeruginosa). The most characteristic signs in chest CT scans were at the beginning of pneumonia with nodules and tree-in-bud often combined with bronchial wall thickening. The following CT scans showed characteristic but not pathognomonic chest CT findings of RSV pneumonia. These morphological findings should be recognized seasonally (winter) especially at the beginning of the case of pneumonia. RSV-associated additional sinusitis is probably common and should be noticed.

  8. Development and evaluation of a Luminex multiplex serology assay to detect antibodies to bovine herpes virus 1, parainfluenza 3 virus, bovine viral diarrhoea virus, and bovine respiratory syncytial virus, with comparison to existing ELISA detection methods.

    Science.gov (United States)

    Anderson, Steve; Wakeley, Phil; Wibberley, Guy; Webster, Kath; Sawyer, Jason

    2011-03-07

    Detection of circulating antibodies to bovine herpes virus 1 (BHV-1), parainfluenza 3 virus (PI3V), bovine viral diarrhoea virus (BVDV) and bovine respiratory syncytial virus (BRSV) using ELISA is widely used for veterinary diagnostics and surveillance. In this paper, the potential of a multiplex serology test based on Luminex technology, where all antibodies are simultaneously detected in a single assay was investigated. The performance of "in-house" separate ELISAs which use relatively crude lysates of cultured virus as capture antigens, was compared to the multiplex assay where the same antigens were covalently bound to the fluorescent beads used in the Luminex platform. A panel of field serum samples was tested by the multiplex assay in parallel with the separate routine ELISAs to provide a comparison between tests. The BHV-1 and PI3V components of the multiplex test showed similar sensitivities and specificities to the separate "in-house" ELISAs. The performance of the BVDV and BRSV components was less successful and was attributed to relatively low signal strength for these antigens, leading to higher assay variability and a reduced ability to distinguish positive and negative samples compared to the "in-house" ELISAs. The results illustrated that antigens commonly used successfully in ELISAs cannot always be transferred for use in alternative assay systems. The use of recombinant BVDV E2 protein was investigated and was shown to lead to an appreciable increase in signal strength compared to the use of crude BVDV antigen in the Luminex system. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  9. Virus-induced exacerbations in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Daisuke eKurai

    2013-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses.COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage.In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.

  10. Identification of Respiratory Syncytial Virus Nonstructural Protein 2 Residues Essential for Exploitation of the Host Ubiquitin System and Inhibition of Innate Immune Responses.

    Science.gov (United States)

    Whelan, Jillian N; Tran, Kim C; van Rossum, Damian B; Teng, Michael N

    2016-07-15

    Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children worldwide. The RSV nonstructural protein 2 (NS2) is a multifunctional protein that primarily acts to antagonize the innate immune system by targeting STAT2 for proteasomal degradation. We investigated the structural determinants of NS2 important for interaction with the host ubiquitin system to degrade STAT2 during infection. We found that NS2 expression enhances ubiquitination of host proteins. Bioinformatics analysis provided a platform for identification of specific residues that limit NS2-induced ubiquitination. Combinations of multiple mutations displayed an additive effect on reducing NS2-induced ubiquitination. Using a reverse genetics system, we generated recombinant RSV (rRSV) containing NS2 ubiquitin mutations, which maintained their effect on ubiquitin expression during infection. Interestingly, STAT2 degradation activity was ablated in the NS2 ubiquitin mutant rRSV. In addition, NS2 ubiquitin mutations decreased rRSV replication, indicating a correlation between NS2's ubiquitin function and antagonism of innate immune signaling to enhance viral replication. Our approach of targeting NS2 residues required for NS2 inhibition of immune responses provides a mechanism for attenuating RSV for vaccine development. RSV has been circulating globally for more than 60 years, causing severe respiratory disease in pediatric, elderly, and immunocompromised populations. Production of a safe, effective vaccine against RSV is a public health priority. The NS2 protein is an effective target for prevention and treatment of RSV due to its antagonistic activity against the innate immune system. However, NS2-deleted RSV vaccine candidates rendered RSV overattenuated or poorly immunogenic. Alternatively, we can modify essential NS2 structural features to marginally limit viral growth while maintaining immune responses, providing the necessary balance between

  11. Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone.

    Science.gov (United States)

    Schmidt, Alexander C; Wenzke, Daniel R; McAuliffe, Josephine M; St Claire, Marisa; Elkins, William R; Murphy, Brian R; Collins, Peter L

    2002-02-01

    Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.

  12. Novel antiviral activity of mung bean sprouts against respiratory syncytial virus and herpes simplex virus -1: an in vitro study on virally infected Vero and MRC-5 cell lines.

    Science.gov (United States)

    Hafidh, Rand R; Abdulamir, Ahmed S; Abu Bakar, Fatimah; Sekawi, Zamberi; Jahansheri, Fatemeh; Jalilian, Farid Azizi

    2015-06-11

    New sources for discovering novel antiviral agents are desperately needed. The current antiviral products are both expensive and not very effective. The antiviral activity of methanol extract of mung bean sprouts (MBS), compared to Ribavarin and Acyclovir, on respiratory syncytial virus (RSV) and Herpes Simplex virus -1 (HSV-1) was investigated using cytotoxicity, virus yield reduction, virucidal activity, and prophylactic activity assays on Vero and MRC-5 cell lines. Moreover, the level of antiviral cytokines, IFNβ, TNFα, IL-1, and IL-6 was assessed in MBS-treated, virally infected, virally infected MBS-treated, and control groups of MRC-5 cells using ELISA. MBS extract showed reduction factors (RF) 2.2 × 10 and 0.5 × 10(2) for RSV and HSV-1, respectively. The 2 h incubation virucidal and prophylactic selectivity indices (SI) of MBS on RSV were 14.18 and 12.82 versus Ribavarin SI of 23.39 and 21.95, respectively, and on HSV-1, SI were 18.23 and 10.9 versus Acyclovir, 22.56 and 15.04, respectively. All SI values were >10 indicating that MBS has a good direct antiviral and prophylactic activities on both RSV and HSV-1. Moreover, interestingly, MBS extract induced vigorously IFNβ, TNFα, IL-1, and IL-6 cytokines in MRC-5 infected-treated group far more than other groups (P < 0.05) and induced TNFα and IL-6 in treated group more than infected group (P < 0.05). MBS extract has potent antiviral and to a lesser extent, prophylactic activities against both RSV and HSV-1, and in case of HSV-1, these activities were comparable to Acyclovir. Part of the underlying mechanism(s) of these activities is attributed to MBS potential to remarkably induce antiviral cytokines in human cells. Hence, we infer that MBS methanol extract could be used as such or as purified active component in protecting and treating RSV and HSV-1 infections. More studies are needed to pinpoint the exact active components responsible for the MBS antiviral activities.

  13. Herpes Simplex Virus 1 Glycoprotein M and the Membrane-Associated Protein UL11 Are Required for Virus-Induced Cell Fusion and Efficient Virus Entry

    Science.gov (United States)

    Kim, In-Joong; Chouljenko, Vladimir N.; Walker, Jason D.

    2013-01-01

    Herpes simplex virus 1 (HSV-1) facilitates virus entry into cells and cell-to-cell spread by mediating fusion of the viral envelope with cellular membranes and fusion of adjacent cellular membranes. Although virus strains isolated from herpetic lesions cause limited cell fusion in cell culture, clinical herpetic lesions typically contain large syncytia, underscoring the importance of cell-to-cell fusion in virus spread in infected tissues. Certain mutations in glycoprotein B (gB), gK, UL20, and other viral genes drastically enhance virus-induced cell fusion in vitro and in vivo. Recent work has suggested that gB is the sole fusogenic glycoprotein, regulated by interactions with the viral glycoproteins gD, gH/gL, and gK, membrane protein UL20, and cellular receptors. Recombinant viruses were constructed to abolish either gM or UL11 expression in the presence of strong syncytial mutations in either gB or gK. Virus-induced cell fusion caused by deletion of the carboxyl-terminal 28 amino acids of gB or the dominant syncytial mutation in gK (Ala to Val at amino acid 40) was drastically reduced in the absence of gM. Similarly, syncytial mutations in either gB or gK did not cause cell fusion in the absence of UL11. Neither the gM nor UL11 gene deletion substantially affected gB, gC, gD, gE, and gH glycoprotein synthesis and expression on infected cell surfaces. Two-way immunoprecipitation experiments revealed that the membrane protein UL20, which is found as a protein complex with gK, interacted with gM while gM did not interact with other viral glycoproteins. Viruses produced in the absence of gM or UL11 entered into cells more slowly than their parental wild-type virus strain. Collectively, these results indicate that gM and UL11 are required for efficient membrane fusion events during virus entry and virus spread. PMID:23678175

  14. Burden of paediatric respiratory syncytial virus disease and potential effect of different immunisation strategies: a modelling and cost-effectiveness analysis for England.

    Science.gov (United States)

    Cromer, Deborah; van Hoek, Albert Jan; Newall, Anthony T; Pollard, Andrew J; Jit, Mark

    2017-08-01

    Vaccines and prophylactic antibodies against respiratory syncytial virus (RSV) are in development and likely to be available in the next 5-10 years. The most efficient way to use these products when they become available is an important consideration for public health decision makers. We performed a multivariate regression analysis to estimate the burden of RSV in children younger than 5 years in England (UK), a representative high-income temperate country, and used these results to assess the potential effect of different RSV immunisation strategies (targeting vaccination for infants, or pregnant women, or prophylactic antibodies for neonates). We did a cost-effectiveness analysis for these strategies, implemented either separately or concurrently, and assessed the effect of restricting vaccination to certain months of the year. We estimated that RSV is responsible for 12 primary care consultations (95% CI 11·9-12·1) and 0·9 admissions to hospital annually per 100 children younger than 5 years (95% CI 0·89-0·90), with the major burden occurring in infants younger than 6 months. The most cost-effective strategy was to selectively immunise all children born before the start of the RSV season (maximum price of £220 [95% uncertainty interval (UI) 208-232] per vaccine, for an incremental cost-effectiveness ratio of £20 000 per quality-adjusted life-year). The maximum price per fully protected person that should be paid for the infant, newborn, and maternal strategies without seasonal restrictions was £192 (95% UI 168-219), £81 (76-86), and £54 (51-57), respectively. Nearly double the number of primary care consultations, and nearly five times the number of admissions to hospital occurred with RSV compared with influenza. RSV vaccine and antibody strategies are likely to be cost-effective if they can be priced below around £200 per fully protected person. A seasonal vaccination strategy is likely to provide the most direct benefits. Herd effects might

  15. Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS triggered by respiratory syncytial virus (RSV infection: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Jun Makino

    2017-01-01

    Full Text Available We present a unique and informative instance of respiratory syncytial virus (RSV infection associated with antiphospholipid syndrome (APS, and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

  16. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison with hemorrhagic pneumonia due to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Salomonsen Charlotte M

    2012-11-01

    Full Text Available Abstract Background Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV has been shown to augment infection with P. aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. Findings We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR and for human RSV by a commercial real-time PCR. RSV was not found. Conclusions This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

  17. Respiratory Syncytial Virus Infection as a Precipitant of Thyroid Storm in a Previously Undiagnosed Case of Graves' Disease in a Prepubertal Girl

    Directory of Open Access Journals (Sweden)

    Charlton RWilliam

    2011-03-01

    Full Text Available Graves' disease is less common in prepubertal than pubertal children, and initial presentation with thyroid storm is rare. We report an 11-year-old prepubertal Hispanic girl who presented with a one-day history of respiratory distress, fever, and dysphagia. She had exophthalmos, a diffuse bilateral goiter and was agitated, tachycardic, and hypertensive. Nasal swab was positive for respiratory syncytial virus (RSV. She was diagnosed with thyroid storm and admitted to the pediatric intensive care unit. While infection is a known precipitant of thyroid storm and RSV is a common pediatric infection, to the best of our knowledge, this is the first reported case of RSV infection apparently precipitating thyroid storm in a prepubertal child.

  18. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa.

    Science.gov (United States)

    Salomonsen, Charlotte M; Breum, Solvej Ø; Larsen, Lars E; Jakobsen, Jeanette; Høiby, Niels; Hammer, Anne S

    2012-11-26

    Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with P. aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR) and for human RSV by a commercial real-time PCR. RSV was not found. This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

  19. Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature.

    Science.gov (United States)

    Makino, Jun; Koshy, Sanjana; Bajaj, Sonal; Jeong, Young-Gwang; Perlman, David C

    2017-01-01

    We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

  20. An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV-associated acute lower respiratory infections in children

    Directory of Open Access Journals (Sweden)

    Simões Eric AF

    2011-04-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV is the leading cause of acute lower respiratory infections (ALRI in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost

  1. An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV)-associated acute lower respiratory infections in children.

    Science.gov (United States)

    Nair, Harish; Verma, Vasundhara R; Theodoratou, Evropi; Zgaga, Lina; Huda, Tanvir; Simões, Eric A F; Wright, Peter F; Rudan, Igor; Campbell, Harry

    2011-04-13

    Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization. We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost; moderate levels of optimism for likelihood of efficacy

  2. Respiratory syncytial virus (RSV)

    Science.gov (United States)

    ... R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases . 8th ... Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle, WA. ...

  3. Respiratory Syncytial Virus

    Science.gov (United States)

    ... Publications Help Archive Site Map Información en español Employee Information Connect with NIAID Facebook Twitter Linkedin Google+ Youtube Flickr Instagram Pinterest Email Website Policies & Notices ...

  4. Clinical and epidemiological aspects related to the detection of adenovirus or respiratory syncytial virus in infants hospitalized for acute lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Eduardo A. Ferone

    2014-01-01

    Full Text Available OBJECTIVE: To characterize and compare clinical, epidemiological, and laboratory aspects ofinfants with acute lower respiratory infection (ALRI associated with the detection of adenovirus(ADV or respiratory syncytial virus (RSV. METHODS: A preliminary respiratory infection surveillance study collected samples of nasopharyngeal aspirate (NPA for viral research, linked to the completion of a standard protocol, from children younger than two years admitted to a university hospital with ALRI, between March of 2008 and August of 2011. Polymerase chain reaction (PCR was used for eight viruses: ADV, RSV, metapneumovirus, Parainfluenza 1, 2, and 3, and Influenza A and B. Cases with NPA collectedduring the first 24 hours of admission, negative results of blood culture, and exclusive detection of ADV (Gadv group or RSV (Grsv group were selected for comparisons. RESULTS: The preliminary study included collection of 1,121 samples of NPA, 813 collected in thefirst 24 hours of admission, of which 50.3% were positive for at least one virus; RSV was identifiedin 27.3% of cases surveyed, and ADV was identified in 15.8%. Among the aspects analyzed inthe Gadv (n = 58 and Grsv (n = 134 groups, the following are noteworthy: the higher meanage, more frequent prescription of antibiotics, and the highest median of total white blood cellcount and C-reactive protein values in Gadv. CONCLUSIONS: PCR can detect persistent/latent forms of ADV, an aspect to be considered wheninterpreting results. Additional studies with quantitative diagnostic techniques could elucidatethe importance of the high frequency observed.

  5. Optimization of one-step duplex real-time RT-PCR for detection of influenza and respiratory syncytial virus in nasopharyngeal aspirates.

    Science.gov (United States)

    de-Paris, Fernanda; Beck, Caroline; Machado, Alice Beatriz Mombach Pinheiro; Paiva, Rodrigo Minuto; da Silva Menezes, Denise; de Souza Nunes, Luciana; Kuchenbecker, Ricardo; Barth, Afonso Luís

    2012-12-01

    Viruses are major contributors to acute respiratory infection-related morbidity and mortality worldwide. The influenza (IF) viruses and human respiratory syncytial virus (RSV) play a particularly important role in the etiology of acute respiratory infections. This study sought to standardize a one-step duplex real-time RT-PCR technique to optimize diagnosis of IFA/IFB and RSVA/RSVB infection. Viral RNA was extracted with the commercially available QIAamp Mini Kit according to manufacturer instructions. RT-PCR was performed with primers to the matrix protein gene of IFA, the hemagglutinin gene of IFB and the N gene of RSVA and RSVB. The limits of detection were 1 copy/μL for IFA, 10 copies/μL for IFB, 5 copies/μL for RSVA, and 250 copies/μL for RSVB. The specificity of RT-PCR was determined by comparison against a panel of several respiratory pathogens. RT-PCR and indirect immunofluorescence (IIF) were compared in a sample of 250 nasopharyngeal aspirates (NPAs) collected during the year 2010. RT-PCR was more sensitive than IIF and able to detect viral co-infections. In summary, RT-PCR optimized for IFA/IFB and RSVA/RSVB is sensitive and specific for these viral agents and is therefore useful for assessment of the etiology of respiratory infections, whether for clinical or epidemiological purposes. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Recombinant respiratory syncytial virus from which the entire SH gene has been deleted grows efficiently in cell culture and exhibits site-specific attenuation in the respiratory tract of the mouse.

    Science.gov (United States)

    Bukreyev, A; Whitehead, S S; Murphy, B R; Collins, P L

    1997-12-01

    The small hydrophobic protein SH of human respiratory syncytial virus (RSV) is a short transmembrane surface protein of unknown function. A full-length cDNA of RSV strain A2 (subgroup A) antigenomic RNA was modified such that the entire SH gene, including the transcription signals and the complete mRNA-encoding sequence, was deleted and replaced by a synthetic intergenic region. This reduced the length of the antigenome by 398 nucleotides and ablated expression of 1 of the 10 RSV mRNAs. Recombinant virus containing this engineered deletion was recovered, and the absence of the SH gene was confirmed by reverse transcription in conjunction with PCR. Northern blot analysis of intracellular RNAs and gel electrophoresis of labeled intracellular proteins confirmed the lack of expression of the SH mRNA and protein. The absence of the SH gene did not noticeably affect RNA replication, but two effects on transcription were noted. First, synthesis of the G, F, and M2 mRNAs was increased, presumably due to their being one position closer to the promoter in the gene order. Second, transcription of genes downstream of the engineered site exhibited a steeper gradient of polarity. On monolayers of HEp-2 cells, the SH-minus virus produced syncytia which were at least equivalent in size to those of the wild type and produced plaques which were 70% larger. Furthermore, the SH-minus virus grew somewhat better (up to 12.6-fold) than wild-type recombinant RSV in certain cell lines. While the function of the SH protein remains to be determined, it seems to be completely dispensable for growth in tissue culture and fusion function. When inoculated intranasally into mice, the SH-minus virus resembled the wild-type recombinant virus in its efficiency of replication in the lungs, whereas it replicated 10-fold less efficiently in the upper respiratory tract. In mice, the SH-minus and wild-type recombinant viruses were similarly immunogenic and effective in inducing resistance to virus

  7. Systematic review and meta-analysis of the effectiveness of commercially available vaccines against bovine herpesvirus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza type 3 virus for mitigation of bovine respiratory disease complex in cattle.

    Science.gov (United States)

    Theurer, Miles E; Larson, Robert L; White, Brad J

    2015-01-01

    To evaluate and analyze data from controlled studies on the effectiveness of vaccinating cattle with commercially available viral antigen vaccines for mitigation of the effects of bovine respiratory disease complex (BRDC). Systematic review and meta-analysis. 31 studies comprising 88 trials. Studies that reported the effectiveness of commercially available bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), and parainfluenza type 3 virus (PI3) vaccines for protection of cattle against BRDC or its components were included in the analysis. Studies or trials were categorized as natural exposure or experimental challenge and were further divided by the viral antigen evaluated and vaccine type (modified-live virus [MLV] or inactivated vaccine). Meta-analysis was performed; summary Mantel-Haenszel risk ratios were determined, and Forest plots were generated. In natural exposure trials, beef calves vaccinated with various antigen combinations had a significantly lower BRDC morbidity risk than did nonvaccinated control calves. In trials evaluating BHV-1 and MLV BVDV vaccines in experimental challenge models, vaccinated calves had a lower BRDC morbidity risk than did control calves; however, in experimental challenge trials evaluating MLV BRSV and PI3 vaccines, no significant difference in morbidity or mortality risk was found between vaccinated and control calves. Estimating clinical efficacy from results of experimental challenge studies requires caution because these models differ substantially from those involving natural exposure. The literature provides data but does not provide sufficiently strong evidence to guide definitive recommendations for determining which virus components are necessary to include in a vaccination program for prevention or mitigation of BRDC in cattle.

  8. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

    International Nuclear Information System (INIS)

    Morton, Craig J.; Cameron, Rachel; Lawrence, Lynne J.; Lin Bo; Lowe, Melinda; Luttick, Angela; Mason, Anthony; McKimm-Breschkin, Jenny; Parker, Michael W.; Ryan, Jane; Smout, Michael; Sullivan, Jayne; Tucker, Simon P.; Young, Paul R.

    2003-01-01

    Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors

  9. The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection.

    Science.gov (United States)

    Bakre, Abhijeet A; Harcourt, Jennifer L; Haynes, Lia M; Anderson, Larry J; Tripp, Ralph A

    2017-07-03

    Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182-186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.

  10. Efficacy of an intranasal modified live bovine respiratory syncytial virus and temperature-sensitive parainfluenza type 3 virus vaccine in 3-week-old calves experimentally challenged with PI3V.

    Science.gov (United States)

    Vangeel, Ilse; Ioannou, Faye; Riegler, Lutz; Salt, Jeremy S; Harmeyer, Silke S

    2009-01-01

    Two experimental parainfluenza type 3 virus (PI3V) challenge studies were undertaken to evaluate the efficacy of a single intranasal dose of an attenuated live vaccine containing modified live bovine respiratory syncytial virus (BRSV) and temperature-sensitive PI3V in 3-week-old calves. In the first study, vaccine efficacy was evaluated in colostrum deprived calves. Nasal shedding of PI3V was highly significantly reduced in vaccinated calves challenged 10 days or 21 days after vaccination. In the second study, vaccine efficacy was assessed in calves with maternal antibodies against PI3V by challenge 66 days post-vaccination. Vaccination also significantly reduced PI3V excretion after challenge in this study. In both studies, clinical signs after challenge were very mild and were not different between vaccinated and control calves.

  11. Grape Seed Proanthocyanidin Inhibits Mucin Synthesis and Viral Replication by Suppression of AP-1 and NF-κB via p38 MAPKs/JNK Signaling Pathways in Respiratory Syncytial Virus-Infected A549 Cells.

    Science.gov (United States)

    Lee, Jin-Woo; Kim, Young Il; Im, Chang-Nim; Kim, Sung Wan; Kim, Su Jin; Min, Seoyeon; Joo, Yong Hoon; Yim, Sung-Vin; Chung, Namhyun

    2017-06-07

    Airway epithelial cells are often infected by respiratory syncytial virus (RSV), one of the most common causes of asthma, bronchiolitis, chronic obstructive pulmonary disease, and pneumonia. During the infection process, excessive mucins instigate airway inflammation. However, the mechanism underlying RSV-induced airway hyper-responsiveness and inflammation is poorly understood. Furthermore, no reliable vaccines or drugs for antiviral therapy are available. In this study, the effect of the natural compound grape seed proanthocyanidin (GSP) on RSV-infected human airway epithelial cells A549 was evaluated. After pretreatment of the cells with or without exposure to RSV with 5-10 μg GSP/mL, the expression of various mucins (MUC1, MUC2, MUC5AC, MUC5B, and MUC8) was evaluated by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting, as well as confocal microscopy. We found that GSP significantly decreased RSV-induced mucin synthesis at the mRNA and protein levels. In addition, GSP suppressed the RSV-induced signaling pathways, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, together with nuclear factor kappa B (NF-κB) and activating protein-1 family members (c-Jun and c-Fos). Concomitantly, GSP inhibited the replication of RSV within A549 cells. Taken together, all our results suggest that GSP could be a potent therapeutic agent to suppress excessive mucus production and viral replication in RSV-induced airway inflammatory disorders.

  12. Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity.

    Directory of Open Access Journals (Sweden)

    Lien Anh Ha Do

    Full Text Available Despite a high burden of respiratory syncytial virus (RSV infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI, focusing on RSV (prevalence, seasonality, subgroups, viral load and its association with disease severity.A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups.Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV, metapneumovirus (MPV, parainfluenza virus (PIV-3 and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity.We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity.

  13. Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity

    Science.gov (United States)

    Bryant, Juliet E.; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; van Doorn, H. Rogier

    2016-01-01

    Background Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. Methods A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. Results Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. Conclusion We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity. PMID:27500954

  14. TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Jesus Segovia

    Full Text Available Human respiratory syncytial virus (RSV constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although "controlled" inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1β (IL-1β plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1β is synthesized as an immature pro-IL-1β form. It is cleaved by activated caspase-1 to yield mature IL-1β that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1β release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1β secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1β production during RSV infection. Further studies illustrated that prior to inflammasome formation; the "first signal" constitutes activation of toll-like receptor-2 (TLR2/MyD88/NF-κB pathway. TLR2/MyD88/NF-κB signaling is required for pro-IL-1β and NLRP3 gene expression during RSV infection. Following expression of these genes, two "second signals" are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS and potassium (K(+ efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-κB pathway (first signal and ROS/potassium efflux (second signal for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1β release during RSV infection.

  15. Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity.

    Science.gov (United States)

    Do, Lien Anh Ha; Bryant, Juliet E; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; van Doorn, H Rogier

    2016-01-01

    Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity.

  16. Neonatal respiratory syncytial virus infection has an effect on lung inflammation and the CD4(+) CD25(+) T cell subpopulation during ovalbumin sensitization in adult mice.

    Science.gov (United States)

    Comas-García, A; López-Pacheco, C P; García-Zepeda, E A; Soldevila, G; Ramos-Martínez, P; Ramos-Castañeda, J

    2016-08-01

    In BALB/c adult mice, respiratory syncytial virus (RSV) infection enhances the degree of lung inflammation before and/or after ovalbumin (OVA) respiratory sensitization. However, it is unclear whether RSV infection in newborn mice has an effect on the immune response to OVA respiratory sensitization in adult mice. The aim of this study was to determine if RSV neonatal infection alters T CD4(+) population and lung inflammation during OVA respiratory sensitization in adult mice. BALB/c mice were infected with RSV on the fourth day of life and challenged by OVA 4 weeks later. We found that in adult mice, RSV neonatal infection prior to OVA sensitization reduces the CD4(+) CD25(+) and CD4(+) CD25(+) forkhead protein 3 (FoxP3)(+) cell populations in the lungs and bronchoalveolar lavage. Furthermore, it also attenuates the inflammatory infiltrate and cytokine/chemokine expression levels in the mouse airways. In conclusion, the magnitude of the immune response to a non-viral respiratory perturbation in adult mice is not enhanced by a neonatal RSV infection. © 2016 British Society for Immunology.

  17. Effect of climate on incidence of respiratory syncytial virus infections in a refugee camp in Kenya: A non-Gaussian time-series analysis.

    Directory of Open Access Journals (Sweden)

    Raymond Nyoka

    Full Text Available Respiratory syncytial virus (RSV is one of the major causes of acute lower respiratory tract infections (ALRTI in children. Children younger than 1 year are the most susceptible to RSV infection. RSV infections occur seasonally in temperate climate regions. Based on RSV surveillance and climatic data, we developed statistical models that were assessed and compared to predict the relationship between weather and RSV incidence among refugee children younger than 5 years in Dadaab refugee camp in Kenya. Most time-series analyses rely on the assumption of Gaussian-distributed data. However, surveillance data often do not have a Gaussian distribution. We used a generalized linear model (GLM with a sinusoidal component over time to account for seasonal variation and extended it to a generalized additive model (GAM with smoothing cubic splines. Climatic factors were included as covariates in the models before and after timescale decompositions, and the results were compared. Models with decomposed covariates fit RSV incidence data better than those without. The Poisson GAM with decomposed covariates of climatic factors fit the data well and had a higher explanatory and predictive power than GLM. The best model predicted the relationship between atmospheric conditions and RSV infection incidence among children younger than 5 years. This knowledge helps public health officials to prepare for, and respond more effectively to increasing RSV incidence in low-resource regions or communities.

  18. Estimating influenza and respiratory syncytial virus-associated mortality in Western Kenya using health and demographic surveillance system data, 2007-2013.

    Science.gov (United States)

    Emukule, Gideon O; Spreeuwenberg, Peter; Chaves, Sandra S; Mott, Joshua A; Tempia, Stefano; Bigogo, Godfrey; Nyawanda, Bryan; Nyaguara, Amek; Widdowson, Marc-Alain; van der Velden, Koos; Paget, John W

    2017-01-01

    Influenza and respiratory syncytial virus (RSV) associated mortality has not been well-established in tropical Africa. We used the negative binomial regression method and the rate-difference method (i.e. deaths during low and high influenza/RSV activity months), to estimate excess mortality attributable to influenza and RSV using verbal autopsy data collected through a health and demographic surveillance system in Western Kenya, 2007-2013. Excess mortality rates were calculated for a) all-cause mortality, b) respiratory deaths (including pneumonia), c) HIV-related deaths, and d) pulmonary tuberculosis (TB) related deaths. Using the negative binomial regression method, the mean annual all-cause excess mortality rate associated with influenza and RSV was 14.1 (95% confidence interval [CI] 0.0-93.3) and 17.1 (95% CI 0.0-111.5) per 100,000 person-years (PY) respectively; and 10.5 (95% CI 0.0-28.5) and 7.3 (95% CI 0.0-27.3) per 100,000 PY for respiratory deaths, respectively. Highest mortality rates associated with influenza were among ≥50 years, particularly among persons with TB (41.6[95% CI 0.0-122.7]); and with RSV were among respiratory deaths. Our study shows a substantial excess mortality associated with influenza and RSV in Western Kenya, especially among children <5 years and older persons with TB, supporting recommendations for influenza vaccination and efforts to develop RSV vaccines.

  19. Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from Vietnamese children identifies distinct patterns of inter- and intra-host evolution

    Science.gov (United States)

    Wilm, Andreas; van Doorn, H. Rogier; Lam, Ha Minh; Sim, Shuzhen; Sukumaran, Rashmi; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Dac, Nguyen Anh Tran; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Binh, Bao Tinh Le; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; Chen, Swaine; Nagarajan, Niranjan; Bryant, Juliet E.; Hibberd, Martin L.

    2015-01-01

    Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children < 2 years of age. Little is known about RSV intra-host genetic diversity over the course of infection or about the immune pressures that drive RSV molecular evolution. We performed whole-genome deep-sequencing on 53 RSV-positive samples (37 RSV subgroup A and 16 RSV subgroup B) collected from the upper airways of hospitalized children in southern Vietnam over two consecutive seasons. RSV A NA1 and RSV B BA9 were the predominant genotypes found in our samples, consistent with other reports on global RSV circulation during the same period. For both RSV A and B, the M gene was the most conserved, confirming its potential as a target for novel therapeutics. The G gene was the most variable and was the only gene under detectable positive selection. Further, positively selected sites in G were found in close proximity to and in some cases overlapped with predicted glycosylation motifs, suggesting that selection on amino acid glycosylation may drive viral genetic diversity. We further identified hotspots and coldspots of intra-host genetic diversity in the RSV genome, some of which may highlight previously unknown regions of functional importance. PMID:26407694

  20. A cost-benefit analysis of the immunisation of children against respiratory syncytial virus (RSV) using the English Hospital Episode Statistics (HES) data set.

    Science.gov (United States)

    Thomas, Gareth

    2018-03-01

    Respiratory syncytial virus (RSV) is a common cause of respiratory infection that is highly prevalent in infants, particularly those with underlying medical conditions. Severe cases of RSV require hospitalisation as well as admission to intensive care and may even result in death. The objective of the study was to measure the net benefits that could arise from an immunisation programme of infants that may well eradicate RSV to a high degree and save the direct and indirect medical care costs from hospitalisation, morbidity and the gain from potential life-time earnings by reducing the probability of mortality. In this context, the majority of existing empirical investigations are based on data from clinical trials, and where relevant facts are not available, a series of strong assumptions is derived from the published literature, whereas in this study, for the first time, the hospital episode statistics database is used to calculate the cost-benefit ratios. The methodology of the analysis adopts a cost-benefit approach to assess the impact of the immunisation and whether it is beneficial to society. The underlying assumptions of the basic model are assessed by adopting a sensitivity analysis. The results show that a number of categories are cost-effective with the use of the passive drug, which means benefits by raising the life expectancy and quality as well as reducing the resource burden on society.

  1. A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Høgh, Mette; Nordbø, Svein

    2008-01-01

    Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children....... We followed 217 children from birth to 1 year of age. Nasal swabs and symptom diaries were collected monthly. Anti-hMPV and anti-RSV IgG antibodies by age 1 year were detected by ELISA, and nasal swabs were analysed for hMPV and RSV by RT-PCR. Logistic regression was used for risk factor analysis....... Anti-hMPV IgG was found in 38 children (17.5%), and anti-RSV IgG in 172 children (79%). Risk factors for being anti-hMPV IgG-positive were: (1) being born in the spring (OR = 2.36; 95% CI:1.06-5.27), and (2) having older siblings (OR = 3.82; 95% CI:1.75-8.34). Risk factors for being anti-RSV Ig...

  2. Seasonality of Influenza and Respiratory Syncytial Viruses and the Effect of Climate Factors in Subtropical-Tropical Asia Using Influenza-Like Illness Surveillance Data, 2010 -2012.

    Directory of Open Access Journals (Sweden)

    Taro Kamigaki

    Full Text Available The seasonality of influenza and respiratory syncytial virus (RSV is well known, and many analyses have been conducted in temperate countries; however, this is still not well understood in tropical countries. Previous studies suggest that climate factors are involved in the seasonality of these viruses. However, the extent of the effect of each climate variable is yet to be defined.We investigated the pattern of seasonality and the effect of climate variables on influenza and RSV at three sites of different latitudes: the Eastern Visayas region and Baguio City in the Philippines, and Okinawa Prefecture in Japan. Wavelet analysis and the dynamic linear regression model were applied. Climate variables used in the analysis included mean temperature, relative and specific humidity, precipitation, and number of rainy days. The Akaike Information Criterion estimated in each model was used to test the improvement of fit in comparison with the baseline model.At all three study sites, annual seasonal peaks were observed in influenza A and RSV; peaks were unclear for influenza B. Ranges of climate variables at the two Philippine sites were narrower and mean variables were significantly different among the three sites. Whereas all climate variables except the number of rainy days improved model fit to the local trend model, their contributions were modest. Mean temperature and specific humidity were positively associated with influenza and RSV at the Philippine sites and negatively associated with influenza A in Okinawa. Precipitation also improved model fit for influenza and RSV at both Philippine sites, except for the influenza A model in the Eastern Visayas.Annual seasonal peaks were observed for influenza A and RSV but were less clear for influenza B at all three study sites. Including additional data from subsequent more years would help to ascertain these findings. Annual amplitude and variation in climate variables are more important than their

  3. RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

    Science.gov (United States)

    Arikkatt, Jaisy; Ullah, Md Ashik; Short, Kirsty Renfree; Zhang, Vivan; Gan, Wan Jun; Loh, Zhixuan; Werder, Rhiannon B; Simpson, Jennifer; Sly, Peter D; Mazzone, Stuart B; Spann, Kirsten M; Ferreira, Manuel AR; Upham, John W; Sukkar, Maria B; Phipps, Simon

    2017-01-01

    Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target. DOI: http://dx.doi.org/10.7554/eLife.21199.001 PMID:28099113

  4. Temporary carriage of bovine coronavirus and bovine respiratory syncytial virus by fomites and human nasal mucosa after exposure to infected calves.

    Science.gov (United States)

    Oma, Veslemøy Sunniva; Klem, Thea; Tråvén, Madeleine; Alenius, Stefan; Gjerset, Britt; Myrmel, Mette; Stokstad, Maria

    2018-01-22

    In order to prevent spread of the endemic pathogens bovine coronavirus (BCoV) and bovine respiratory syncytial virus (BRSV) between herds, knowledge of indirect transmission by personnel and fomites is fundamental. The aims of the study were to determine the duration of viral RNA carriage and the infectivity of viral particles on fomites and human nasal mucosa after exposure to BCoV and BRSV. During two animal infection experiments, swabs were collected from personnel (nasal mucosa) and their clothes, boots and equipment after contact with calves shedding either virus. Viral RNA was quantified by RT-qPCR or droplet digital RT-PCR (RT-ddPCR), and selected samples with high levels of viral RNA were tested by cell culture for infectivity. For BCoV, 46% (n = 80) of the swabs from human nasal mucosa collected 30 min after exposure were positive by RT-qPCR. After two, four and six hours, 15%, 5% and 0% of the swabs were positive, respectively. Infective virions were not detected in mucosal swabs (n = 2). A high viral RNA load was detected on 97% (n = 44) of the fomites 24 h after exposure, and infective virions were detected in two of three swabs. For BRSV, 35% (n = 26) of the human nasal mucosa swabs collected 30 min after exposure, were positive by RT-ddPCR, but none were positive for infective virions. Of the fomites, 89% (n = 38) were positive for BRSV RNA 24 h after exposure, but all were negative for infective viruses. The results indicate that human nasal mucosa can carry both BCoV and BRSV RNA after exposure to virus shedding calves, but the carriage seems short-lived and the transmission potential is likely limited. High viral loads on contaminates fomites 24 h after exposure to infected animals, and detection of infective BCoV, indicate that contaminated fomites represent a significant risk for indirect transmission between herds.

  5. Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation.

    Science.gov (United States)

    Blais, Normand; Gagné, Martin; Hamuro, Yoshitomo; Rheault, Patrick; Boyer, Martine; Steff, Ann-Muriel; Baudoux, Guy; Dewar, Vincent; Demers, Josée; Ruelle, Jean-Louis; Martin, Denis

    2017-07-01

    The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen. IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F

  6. Use of palivizumab and infection control measures to control an outbreak of respiratory syncytial virus in a neonatal intensive care unit confirmed by real-time polymerase chain reaction.

    LENUS (Irish Health Repository)

    O'Connell, K

    2011-04-01

    Respiratory syncytial virus (RSV) is a potentially life-threatening infection in premature infants. We report an outbreak involving four infants in the neonatal intensive care unit (NICU) of our hospital that occurred in February 2010. RSV A infection was confirmed by real-time polymerase chain reaction. Palivizumab was administered to all infants in the NICU. There were no additional symptomatic cases and repeat RSV surveillance confirmed that there was no further cross-transmission within the unit. The outbreak highlighted the infection control challenge of very high bed occupancy in the unit and the usefulness of molecular methods in facilitating detection and management.

  7. Virus-induced chalazion.

    Science.gov (United States)

    Mansour, A M; Chan, C-C; Crawford, M A; Tabbarah, Z A; Shen, D; Haddad, W F; Salti, I; Ghazi, N G

    2006-02-01

    To investigate a viral etiology in certain chalazia. A prospective study over 7.5 years of all newly presenting chalazia associated with diffuse follicular conjunctivitis but without any other aetiological factors. Patients were investigated for ocular or systemic infections by history, physical exam, slit-lamp exam, and/or histology of conjunctival biopsy (including transmission electron microscopy). A total of 27 patients developed follicular conjunctivitis without meibomian gland dysfunction, blepharitis, or sexually transmitted diseases. Evidence for a viral aetiology included: recent systemic viral illness (15/27), recent contact with subjects with chalazia or follicular conjunctivitis (5/27), preauricular lymphadenopathy (4/27), viral corneal disease (4/27), or viral particles by ultrastructure (4/4). Chalazia may be associated with viral conjunctivitis. Intralesional corticosteroids should be considered with great caution for viral-induced chalazia.

  8. Influenza and respiratory syncytial virus in infants study (IRIS) of hospitalized and non-ill infants aged <1 year in four countries: study design and methods.

    Science.gov (United States)

    Thompson, Mark G; Hunt, Danielle R; Arbaji, Ali K; Simaku, Artan; Tallo, Veronica L; Biggs, Holly M; Kulb, Carolyn; Gordon, Aubree; Khader, Ilham Abu; Bino, Silvia; Lucero, Marilla G; Azziz-Baumgartner, Eduardo; Shifflett, Pat; Sanchez, Felix; Marar, Basima I; Bakalli, Ilirjana; Simões, Eric A F; Levine, Min Z; Meece, Jennifer K; Balmaseda, Angel; Al-Sanouri, Tareq M; Dhimolea, Majlinda; de Jesus, Joanne N; Thornburg, Natalie J; Gerber, Susan I; Gresh, Lionel

    2017-03-22

    This multi-country prospective study of infants aged respiratory syncytial virus (RSV) infections associated with hospitalizations, to describe clinical features and antibody response to infection, and to examine predictors of very severe disease requiring intensive care. We are enrolling a hospital-based cohort and a sample of non-ill infants in four countries (Albania, Jordan, Nicaragua, and the Philippines) using a common protocol. We are currently starting year 2 of a 2- to 3-year study and will enroll approximately 3,000 infants hospitalized for any acute illness (respiratory or non-respiratory) during periods of local influenza and/or RSV circulation. After informed consent and within 24 h of admission, we collect blood and respiratory specimens and conduct an interview to assess socio-demographic characteristics, medical history, and symptoms of acute illness (onset ≤10 days). Vital signs, interventions, and medications are documented daily through medical record abstraction. A follow-up health assessment and collection of convalescent blood occurs 3-5 weeks after enrollment. Influenza and RSV infection is confirmed by singleplex real time reverse transcriptase polymerase chain reaction (rRT-PCR) assays. Serologic conversion will be assessed comparing acute and convalescent sera using hemagglutination inhibition assay for influenza antibodies and enzyme-linked immunosorbent assay (ELISA) for RSV. Concurrent with hospital-based enrollment, respiratory specimens are also being collected (and tested by rRT-PCR) from approximately 1,400 non-ill infants aged <1 year during routine medical or preventive care. The Influenza and RSV in Infants Study (IRIS) promises to expand our knowledge of the frequency, clinical features, and antibody profiles of serious influenza and RSV disease among infants aged <1 year, quantify the proportion of infections that may be missed by traditional surveillance, and inform decisions about the potential value of existing and new

  9. Neonatal CD8 T-cell hierarchy is distinct from adults and is influenced by intrinsic T cell properties in respiratory syncytial virus infected mice.

    Directory of Open Access Journals (Sweden)

    Tracy J Ruckwardt

    2011-12-01

    Full Text Available Following respiratory syncytial virus infection of adult CB6F1 hybrid mice, a predictable CD8+ T cell epitope hierarchy is established with a strongly dominant response to a K(d-restricted peptide (SYIGSINNI from the M2 protein. The response to K(dM2(82-90 is ∼5-fold higher than the response to a subdominant epitope from the M protein (NAITNAKII, D(bM(187-195. After infection of neonatal mice, a distinctly different epitope hierarchy emerges with codominant responses to K(dM2(82-90 and D(bM(187-195. Adoptive transfer of naïve CD8+ T cells from adults into congenic neonates prior to infection indicates that intrinsic CD8+ T cell factors contribute to age-related differences in hierarchy. Epitope-specific precursor frequency differs between adults and neonates and influences, but does not predict the hierarchy following infection. Additionally, dominance of K(dM2(82-90-specific cells does not correlate with TdT activity. Epitope-specific Vβ repertoire usage is more restricted and functional avidity is lower in neonatal mice. The neonatal pattern of codominance changes after infection at 10 days of age, and rapidly shifts to the adult pattern of extreme K(dM2(82-90-dominance. Thus, the functional properties of T cells are selectively modified by developmental factors in an epitope-specific and age-dependent manner.

  10. A prospective, open-label, non-comparative study of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus disease in the Russian Federation

    Directory of Open Access Journals (Sweden)

    Turti Tatyana V

    2012-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a leading cause of lower respiratory tract infections (LRTIs in children globally. Predisposing conditions for the development of serious RSV disease include preterm infants and those with cardiopulmonary illness, including congenital heart disease (CHD and bronchopulmonary dysplasia (BPD. No vaccine is currently approved for the prevention of RSV infection. It is recommended that children at high risk be prophylactically administered palivizumab, a monoclonal antibody that has been shown in a number of clinical studies to reduce hospitalization rates due to serious RSV infection. The objective of the current study was to determine the safety and effectiveness of palivizumab in preventing serious RSV disease in high-risk children in the Russian Federation. Children at high risk of serious RSV disease (ie, born at ≤35 wk gestational age and ≤6 mo of age, and/or aged ≤24 mo with BPD or hemodynamically significant CHD were enrolled. Subjects were to receive 3 to 5 monthly injections of palivizumab 15 mg/kg (depending on the month of the initial injection over the RSV season. The primary endpoint was RSV-related hospitalizations. Adverse events (AEs were reported through 100 days following the final injection. Results One hundred subjects received ≥1 injection of palivizumab; 94 completed their dosing schedule. There were no RSV hospitalizations or deaths. Six of 7 subjects hospitalized for respiratory/cardiac conditions had an RSV test, which was negative in all cases. Three non-serious AEs (acute intermittent rhinitis and rhinitis, 1 subject; atopic dermatitis, 1 subject were considered possibly related to palivizumab. All other AEs were mild or moderate and considered not related/probably not related to palivizumab. Conclusion Palivizumab was generally well tolerated and effectively prevented serious RSV infection in a mixed population of high-risk children in the Russian

  11. Epidemiology, clinical characteristics, laboratory findings and severity of respiratory syncytial virus acute lower respiratory infection in Malaysian children, 2008-2013.

    Science.gov (United States)

    Ng, Khuen F; Tan, Kah K; Sam, Zhi H; Ting, Grace Ss; Gan, Wan Y

    2017-04-01

    The aim of this study is to describe epidemiology, clinical features, laboratory data and severity of respiratory syncytial virus (RSV) acute lower respiratory infection (ALRI) in Malaysian children and to determine risk factors associated with prolonged hospital stay, paediatric intensive care unit (PICU) admission and mortality. Retrospective data on demographics, clinical presentation, outcomes and laboratory findings of 450 children admitted into Tuanku Jaafar Hospital in Seremban, Malaysia from 2008 to 2013 with documented diagnosis of RSV ALRI were collected and analysed. Most admissions were children below 2 years old (85.8%; 386/450). Commonest symptoms were fever (84.2%; 379/450), cough (97.8%; 440/450) and rhinorrhea (83.6%; 376/450). The median age among febrile patients (n = 379) was 9.0 months with interquartile range (IQR) of 4.0-19.0 months whereas the median age among those who were apyrexial (n = 71) was 2 months with IQR of 1-6 months (P-value history of prematurity, chronic comorbidity and thrombocytosis were significantly associated with prolonged hospital stay, PICU admission and mortality. Infants less than 6 months old with RSV ALRI tend to be afebrile at presentation. Younger age, history of prematurity, chronic comorbidity and thrombocytosis are predictors of severe RSV ALRI among Malaysian children. Case fatality rate for Malaysian children below 5 years of age with RSV ALRI in our centre is higher than what is seen in developed countries, suggesting that there is room for improvement. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  12. Differential impact of respiratory syncytial virus and parainfluenza virus on the frequency of acute otitis media is explained by lower adaptive and innate immune responses in otitis-prone children.

    Science.gov (United States)

    Verhoeven, David; Xu, Qingfu; Pichichero, Michael E

    2014-08-01

    Acute otitis media (AOM) is a leading cause of bacterial pediatric infections associated with viral upper respiratory infections (URIs). We examined the differential impact of respiratory syncytial virus (RSV) and parainfluenza virus URIs on the frequency of AOM caused by Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi) in stringently defined otitis-prone (sOP) and non-otitis-prone (NOP) children as a potential mechanism to explain increased susceptibility to AOM. Peripheral blood and nasal washes were obtained from sOP and NOP children (n = 309). Colonization events and antiviral responses consisting of total specific immunoglobulin G (IgG) responses, neutralizing antibody responses, and T-cell responses were determined. Isolated neutrophils were infected with varying multiplicities of infection of both viruses, and opsonophagocytosis potential was measured. A significant increase was found in frequency of AOM events caused by Spn and NTHi, with a concurrent RSV infection in sOP children. These results correlated with diminished total RSV-specific IgG, higher viral nasal burdens, and lower IgG neutralizing capacity. The sOP children had diminished T-cell responses to RSV that correlated with lower Toll-like receptor 3/7 transcript and decreased expression of HLA-DR on antigen-presenting cells. RSV interfered with the Spn phagocytic capacity of neutrophils in a dose-dependent manner. Parainfluenza virus infections did not differentially affect AOM events in sOP and NOP children. Lower innate and adaptive immune responses to RSV in sOP children may slow the kinetics of viral clearance from the nasopharynx and allow for viral interference with antibacterial immune responses, thus contributing to increased frequency of AOMs. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes.

    Directory of Open Access Journals (Sweden)

    Samantha K Dunmire

    Full Text Available Epstein-Barr Virus (EBV causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza, respiratory syncytial virus (RSV, human rhinovirus (HRV, attenuated yellow fever virus (YFV, and Dengue fever virus (DENV, revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.

  14. A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice.

    Science.gov (United States)

    Céspedes, Pablo F; Rey-Jurado, Emma; Espinoza, Janyra A; Rivera, Claudia A; Canedo-Marroquín, Gisela; Bueno, Susan M; Kalergis, Alexis M

    2017-02-01

    Human respiratory syncytial virus (hRSV) is a major health burden worldwide, causing the majority of hospitalizations in children under two years old due to bronchiolitis and pneumonia. HRSV causes year-to-year outbreaks of disease, which also affects the elderly and immunocompromised adults. Furthermore, both hRSV morbidity and epidemics are explained by a consistently high rate of re-infections that take place throughout the patient life. Although significant efforts have been invested worldwide, currently there are no licensed vaccines to prevent hRSV infection. Here, we describe that a recombinant Bacillus Calmette-Guerin (BCG) vaccine expressing the nucleoprotein (N) of hRSV formulated under current good manufacture practices (cGMP rBCG-N-hRSV) confers protective immunity to the virus in mice. Our results show that a single dose of the GMP rBCG-N-hRSV vaccine retains its capacity to protect mice against a challenge with a disease-causing infection of 1×10 7 plaque-forming units (PFUs) of the hRSV A2 clinical strain 13018-8. Compared to unimmunized infected controls, vaccinated mice displayed reduced weight loss and less infiltration of neutrophils within the airways, as well as reduced viral loads in bronchoalveolar lavages, parameters that are characteristic of hRSV infection in mice. Also, ex vivo re-stimulation of splenic T cells at 28days post-immunization activated a repertoire of T cells secreting IFN-γ and IL-17, which further suggest that the rBCG-N-hRSV vaccine induced a mixed, CD8 + and CD4 + T cell response capable of both restraining viral spread and preventing damage of the lungs. All these features support the notion that rBCG-N-hRSV is a promising candidate vaccine to be used in humans to prevent the disease caused by hRSV in the susceptible population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. CT-morphological characterization of respiratory syncytial virus (RSV) pneumonia in immune-compromised adults; Morphologische Charakterisierung und Verlaufsbeurteilung von Respiratory Syncytial Virus (RSV) Pneumonien bei immunkompromittierten Erwachsenen in der Thorax-CT

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, J.L.; Kauczor, H.U. [Univ. Hospital Heidelberg (Germany). Diagnostic and Interventional Radiology; Lehners, N.; Egerer, G. [Univ. Hospital Heidelberg (Germany). Internal Medicine V of Hematology, Oncoloy and Rheumatology; Heussel, C.P. [Thoracic Hospital at Univ. Hospital Heidelberg (Germany). Diagnostic and Interventional Radiology with Nuclear Medicine

    2014-07-15

    Characterization and follow-up evaluation of chest CT of RSV pneumonia in immune-compromised adults during a seasonal epidemic. Retrospective analysis of 132 chest CT examinations of 51 adult immune-compromised patients (29 m/22f, diameter 58 years) with clinical signs of pneumonia and positive RSV test in winter 2011/2012. Two experienced chest radiologists evaluated the morphology (bronchial wall thickening, tree-in-bud, nodules, halo, ground-glass opacities, consolidations, pleural fluid) of the CT scans by consensus. Pathological findings were in 86 % of the chest CT scans: Areas of ground-glass attenuation in 64 %, consolidations in 56 %, nodules in 55 % (diameter 8 mm in maximal diameter, with halo in 71 %), pleural fluid in 44 % (diameter 2 cm), tree-in-bud in 36 %, bronchial wall thickening in 27 % and more than one morphological finding in 72 %. There were no pathological CT findings in 14 % of patients with clinical symptoms of pneumonia because these patients did not undergo follow-up. Radiological progression was found in 45 % of patients and regression in 33 % in follow-up examinations. In 37 % an additional examination of the paranasal sinuses was performed and showed sinusitis in 63 % of cases. 90 % of the patients had sinusitis as well as pneumonia. In addition to RSV, a further pathogenic agent was found in bronchoalveolar lavage of five patients (Aspergillus spec., herpes simplex virus, Pseudomonas aeruginosa). The most characteristic signs in chest CT scans were at the beginning of pneumonia with nodules and tree-in-bud often combined with bronchial wall thickening. The following CT scans showed characteristic but not pathognomonic chest CT findings of RSV pneumonia. These morphological findings should be recognized seasonally (winter) especially at the beginning of the case of pneumonia. RSV-associated additional sinusitis is probably common and should be noticed.

  16. Cost-utility analysis of Palivizumab for Respiratory Syncytial Virus infection prophylaxis in preterm infants: update based on the clinical evidence in Spain.

    Science.gov (United States)

    Sanchez-Luna, M; Burgos-Pol, R; Oyagüez, I; Figueras-Aloy, J; Sánchez-Solís, M; Martinón-Torres, F; Carbonell-Estrany, X

    2017-10-17

    This study aimed at estimating the efficiency of palivizumab in the prevention of Respiratory Syncytial Virus (RSV) infection and its sequelae in preterm infants (32 day 1 -35 day 0 weeks of gestational age -wGA-) in Spain. A decision-tree model was developed to compare health benefits (Quality Adjusted Life Years-QALYs) and costs of palivizumab versus a non-prophylaxis strategy over 6 years. A hypothetical cohort of 1,000 preterm infants, 32 day 1 -35 day 0 wGA (4.356 kg average weight) at the beginning of the prophylaxis (15 mg/kg of palivizumab; 3.88 average number of injections per RSV season) was analysed. The model considered the most recent evidence from Spanish observational and epidemiological studies on RSV infection: the FLIP II study provided hospital admission and Intensive Care Unit (ICU) admission rates; in-hospital mortality rate was drawn from an epidemiological study from 2004 to 2012; recurrent wheezing rates associated to RSV infection from SPRING study were adjusted by the evidence on the palivizumab effect from clinical trials. Quality of life baseline value, number of hospitalized infants and the presence of recurrent wheezing over time were granted to estimate QALYs. National Health Service and societal perspective (included also recurrent wheezing indirect cost) were analysed. Total costs (€, 2016) included pharmaceutical and administration costs, hospitalization costs and recurrent wheezing management annual costs. A discount rate of 3.0% was applied annually for both costs and health outcomes. Over 6 years, the base case analysis showed that palivizumab was associated to an increase of 0.0731 QALYs compared to non-prophylaxis. Total costs were estimated in €2,110.71 (palivizumab) and €671.68 (non-prophylaxis) from the National Health System (NHS) perspective, resulting in an incremental cost utility ratio (ICUR) of €19,697.69/QALYs gained (prophylaxis vs non-prophylaxis). Results derived from the risk-factors population

  17. A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV prophylaxis with motavizumab and palivizumab administered in the same season

    Directory of Open Access Journals (Sweden)

    Griffin M Pamela

    2010-06-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is an important pathogen causing annual epidemics of bronchiolitis and pneumonia among infants worldwide. High-risk infants currently receive RSV prophylaxis with palivizumab, a humanized RSV monoclonal antibody (MAb. In preclinical in vitro and in vivo (cotton-rat model studies, motavizumab, a new RSV MAb, was shown to have greater anti-RSV activity than palivizumab. Motavizumab is currently under review for licensing approval. Since both MAbs may be available concurrently, this study evaluated their safety and tolerability when administered sequentially during the same RSV season. Methods Between April 2006 and May 2006, 260 high-risk infants were randomly assigned 1:1:1 to receive monthly intramuscular injections: 2 doses of motavizumab followed by 3 doses of palivizumab (M/P; 2 doses of palivizumab followed by 3 doses of motavizumab (P/M; or 5 doses of motavizumab (control. Adverse events (AEs, serious AEs [SAEs], development of antidrug antibody (ADA, and serum drug trough concentrations were assessed. Results Most children received all 5 doses (246/260 [94.6%] and completed the study (241/260 [92.7%]. While overall AE rates were similar (mostly level 1 or 2 in severity, SAEs and level 3 AEs occurred more frequently in the M/P group (SAEs: 22.9% M/P, 8.4% P/M, 11.8% motavizumab only; level 3 AEs: 15.7% M/P, 6.0% P/M, 6.5% motavizumab only. This trend in AE rates occurred before and after switching from motavizumab to palivizumab, suggesting a cause other than the combined regimen. Frequencies of AEs judged by the investigator to be related to study drug were similar among groups. Two deaths occurred on study (both in the M/P group, before palivizumab administration; neither was considered by the site investigator to be related to study drug. Mean serum drug trough concentrations were comparable among groups; ADA detection was infrequent (5.1% or less of any group. Conclusions The

  18. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta–analysis

    Directory of Open Access Journals (Sweden)

    Ting Shi

    2015-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most common pathogen identified in young children with acute lower respiratory infection (ALRI as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV–associated ALRI. We aimed to identify risk factors for RSV–associated ALRI in young children. We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta–analyses to estimate odds ratios with 95% confidence intervals (CI for individual risk factors. We identified 20 studies (3 were unpublished data with “good quality” that investigated 18 risk factors for RSV–associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV–associated ALRI. The meta–estimates of their odds ratio (ORs with corresponding 95% confidence intervals (CI are prematurity 1.96 (95% CI 1.44–2.67, low birth weight 1.91 (95% CI 1.45–2.53, being male 1.23 (95% CI 1.13–1.33, having siblings 1.60 (95% CI 1.32–1.95, maternal smoking 1.36 (95% CI 1.24–1.50, history of atopy 1.47 (95% CI 1.16–1.87, no breastfeeding 2.24 (95% CI 1.56–3.20 and crowding 1.94 (95% CI 1.29–2.93. Although there were insufficient studies available to generate a meta–estimate for HIV, all articles (irrespective of quality scores reported significant associations between HIV and RSV–associated ALRI. This study presents a comprehensive report of the strength of association between various socio–demographic risk factors and RSV–associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause ALRI and

  19. Relationship between the loss of neutralizing antibody binding and fusion activity of the F protein of human respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Sarisky Robert T

    2007-07-01

    Full Text Available Abstract To elucidate the relationship between resistance to HRSV neutralizing antibodies directed against the F protein and the fusion activity of the F protein, a recombinant approach was used to generate a panel of mutations in the major antigenic sites of the F protein. These mutant proteins were assayed for neutralizing mAb binding (ch101F, palivizumab, and MAb19, level of expression, post-translational processing, cell surface expression, and fusion activity. Functional analysis of the fusion activity of the panel of mutations revealed that the fusion activity of the F protein is tolerant to multiple changes in the site II and IV/V/VI region in contrast with the somewhat limited spectrum of changes in the F protein identified from the isolation of HRSV neutralizing antibody virus escape mutants. This finding suggests that aspects other than fusion activity may limit the spectrum of changes tolerated within the F protein that are selected for by neutralizing antibodies.

  20. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Faden, H.; Hong, J.J.; Ogra, P.L.

    1986-03-01

    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with /sup 3/H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P < 0.01) enhanced by prior RSV infection. The degree of adherence was directly related to the amount of viral antigen expressed on the cell surface. The adherence was temperature dependent, with maximal adherence observed at 37/sup 0/C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP.

  1. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

    International Nuclear Information System (INIS)

    Faden, H.; Hong, J.J.; Ogra, P.L.

    1986-01-01

    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with 3 H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P 0 C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP

  2. Respiratory Commensal Bacteria Corynebacterium pseudodiphtheriticum Improves Resistance of Infant Mice to Respiratory Syncytial Virus and Streptococcus pneumoniae Superinfection

    Directory of Open Access Journals (Sweden)

    Paulraj Kanmani

    2017-08-01

    Full Text Available Corynebacterium pseudodiphtheriticum is a Gram-positive bacterium found as a member of the normal microbiota of the upper respiratory tract. It was suggested that C. pseudodiphtheriticum may be potentially used as a next-generation probiotic for nasal application, although no deep studies were performed in this regard. We hypothesized that human isolate C. pseudodiphtheriticum strain 090104 is able to modulate the respiratory innate immune response and beneficially influence the resistance to viral and bacterial infections. Therefore, in the present study we investigated how the exposure of infant mice to nasal priming with viable or non-viable C. pseudodiphtheriticum 090104 influences the respiratory innate immune response triggered by Toll-like receptor (TLR-3 activation, the susceptibility to primary Respiratory Synsytial Virus (RSV infection, and the resistance to secondary Streptococcus pneumoniae pneumonia. We demonstrated that the nasal priming with viable C. pseudodiphtheriticum 090104 differentially modulated TLR3-mediated innate antiviral immune response in the respiratory tract of infant mice, improving their resistance to primary RSV infection, and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, we found that viable C. pseudodiphtheriticum improved lung CD3+CD4+IFN-γ+, and CD3+CD4+IL-10+ T cells as well as CD11c+SiglecF+IFN-β+ alveolar macrophages. Of interest, non-viable bacteria did not have the same protective effect, suggesting that C. pseudodiphtheriticum colonization is needed for achieving its protective effect. In conclusion, we present evidence that nasal application of viable C. pseudodiphtheriticum could be thought as an alternative to boost defenses against RSV and secondary pneumococcal pneumonia, which should be further studied and validated in clinical trials. Due to the absence of a long-lasting immunity, re-infection with RSV throughout life is common

  3. Respiratory syncytial virus (RSV infection in elderly mice results in altered antiviral gene expression and enhanced pathology.

    Directory of Open Access Journals (Sweden)

    Terianne M Wong

    Full Text Available Elderly persons are more susceptible to RSV-induced pneumonia than young people, but the molecular mechanism underlying this susceptibility is not well understood. In this study, we used an aged mouse model of RSV-induced pneumonia to examine how aging alters the lung pathology, modulates antiviral gene expressions, and the production of inflammatory cytokines in response to RSV infection. Young (2-3 months and aged (19-21 months mice were intranasally infected with mucogenic or non-mucogenic RSV strains, lung histology was examined, and gene expression was analyzed. Upon infection with mucogenic strains of RSV, leukocyte infiltration in the airways was elevated and prolonged in aged mice compared to young mice. Minitab factorial analysis identified several antiviral genes that are influenced by age, infection, and a combination of both factors. The expression of five antiviral genes, including pro-inflammatory cytokines IL-1β and osteopontin (OPN, was altered by both age and infection, while age was associated with the expression of 15 antiviral genes. Both kinetics and magnitude of antiviral gene expression were diminished as a result of older age. In addition to delays in cytokine signaling and pattern recognition receptor induction, we found TLR7/8 signaling to be impaired in alveolar macrophages in aged mice. In vivo, induction of IL-1β and OPN were delayed but prolonged in aged mice upon RSV infection compared to young. In conclusion, this study demonstrates inherent differences in response to RSV infection in young vs. aged mice, accompanied by delayed antiviral gene induction and cytokine signaling.

  4. Comparison of levels and duration of detection of antibodies to bovine viral diarrhea virus 1, bovine viral diarrhea virus 2, bovine respiratory syncytial virus, bovine herpesvirus 1, and bovine parainfluenza virus 3 in calves fed maternal colostrum or a colostrum-replacement product.

    Science.gov (United States)

    Chamorro, Manuel F; Walz, Paul H; Haines, Deborah M; Passler, Thomas; Earleywine, Thomas; Palomares, Roberto A; Riddell, Kay P; Galik, Patricia; Zhang, Yijing; Givens, M Daniel

    2014-04-01

    Colostrum-replacement products are an alternative to provide passive immunity to neonatal calves; however, their ability to provide adequate levels of antibodies recognizing respiratory viruses has not been described. The objective of this study was to compare the serum levels of IgG at 2 d of age and the duration of detection of antibodies to bovine viral diarrhea virus 1 (BVDV-1), bovine viral diarrhea virus 2 (BVDV-2), bovine respiratory syncytial virus (BRSV), bovine herpesvirus 1 (BHV-1), and bovine parainfluenza virus 3 (BPIV-3) in calves fed maternal colostrum (MC) or a colostrum replacement (CR) at birth. Forty newborn male Holstein calves were assigned to the CR or the MC group. Group CR (n = 20) received 2 packets of colostrum replacement (100 g of IgG per 470-g packet), while group MC (n = 20) received 3.8 L of maternal colostrum. Blood samples for detection of IgG and virus antibodies were collected from each calf at birth, at 2 and 7 d, and monthly until the calves became seronegative. Calves in the MC group had greater IgG concentrations at 2 d of age. The apparent efficiency of absorption of IgG was greater in the MC group than in the CR group, although the difference was not significant. Calves in the CR group had greater concentrations of BVDV neutralizing antibodies during the first 4 mo of life. The levels of antibodies to BRSV, BHV-1, and BPIV-3 were similar in the 2 groups. The mean time to seronegativity was similar for each virus in the 2 groups; however, greater variation was observed in the antibody levels and in the duration of detection of immunity in the MC group than in the CR group. Thus, the CR product provided calves with more uniform levels and duration of antibodies to common bovine respiratory viruses.

  5. [INF-gamma during respiratory-syncytial induced obstructive respiratory syndrome in infection in children under one year of age].

    Science.gov (United States)

    Kandelaki, E T; Nemsadze, K P; Chkhaidze, I G; Kherkheulidze, M N; Kamkamidze, G K

    2005-12-01

    Lately the connection of Asthma and RSV drew the sufficient attention. The recurrent wheezing developed during the RSV in children is particularly frequent in the families having history of atopy. The decreased expression of INFgamma may play the role in the pathogenesis of RSV infection. The target of our research was the study of the rate of INFgamma during various clinical courses of RSV-infection and definition of its role in the pathogenesis of ARVI. 52 children with RSV-associated wheezing have been studied, who had first (32) or recurrent episode (20) of bronchial obstruction and whose families had occurrence of atopy. 52 children with non RSV-associated wheezing (III group) and 10 healthy children up to 12 months of age (IV group) were considered as the control groups. Children from all four groups were from families with the history of atopy. INFgamma was measured by enzyme immunoassay (ELISA). Comparison of two groups of wheezing children with RSV infection showed significant reduction of INFgamma level in the group of children with recurrent wheezing vs. the group with first episode of wheezing. INFgamma levels were significantly higher in the two control groups. During the acute respiratory infection induced by RS-virus, which proceeds with the obstruction of respiratory tract (wheezing), reduction of INFgamma was noted and higher frequency of wheezing episodes is associated with more prominent alteration.

  6. Inhibitory Effect of Ferulic Acid and Isoferulic Acid on the Production of Macrophage Inflammatory Protein-2 in Response to Respiratory Syncytial Virus Infection in RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    S. Sakai

    1999-01-01

    Full Text Available We investigated the effect of ferulic acid (FA and isoferulic acid (IFA, which are the main active components of the rhizoma of Cimicifuga heracleifolia (CH, an anti-inflammatory drug used frequently in Japanese traditional medicine, on the production of macrophage inflammatory protein-2 (MIR-2 in a murine macrophage cell line, RAW264.7, in response to respiratory syncytial virus (RSV infection. Following the exposure of cells to RSV for 20 h, the MIP-2 level in condition medium was increased to about 20 ng/ml, although this level in mock-infected cells was negligible. In the presence of either FA or IFA, RSV-infected cells reduced MIP-2 production in a dose-dependent manner. These data suggest that FA and IFA might be responsible, at least in part, for the anti-inflammatory drug effect of CH extract through the inhibition of MIP-2 production.

  7. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

    Science.gov (United States)

    Shi, Ting; McAllister, David A; O'Brien, Katherine L; Simoes, Eric A F; Madhi, Shabir A; Gessner, Bradford D; Polack, Fernando P; Balsells, Evelyn; Acacio, Sozinho; Aguayo, Claudia; Alassani, Issifou; Ali, Asad; Antonio, Martin; Awasthi, Shally; Awori, Juliet O; Azziz-Baumgartner, Eduardo; Baggett, Henry C; Baillie, Vicky L; Balmaseda, Angel; Barahona, Alfredo; Basnet, Sudha; Bassat, Quique; Basualdo, Wilma; Bigogo, Godfrey; Bont, Louis; Breiman, Robert F; Brooks, W Abdullah; Broor, Shobha; Bruce, Nigel; Bruden, Dana; Buchy, Philippe; Campbell, Stuart; Carosone-Link, Phyllis; Chadha, Mandeep; Chipeta, James; Chou, Monidarin; Clara, Wilfrido; Cohen, Cheryl; de Cuellar, Elizabeth; Dang, Duc-Anh; Dash-Yandag, Budragchaagiin; Deloria-Knoll, Maria; Dherani, Mukesh; Eap, Tekchheng; Ebruke, Bernard E; Echavarria, Marcela; de Freitas Lázaro Emediato, Carla Cecília; Fasce, Rodrigo A; Feikin, Daniel R; Feng, Luzhao; Gentile, Angela; Gordon, Aubree; Goswami, Doli; Goyet, Sophie; Groome, Michelle; Halasa, Natasha; Hirve, Siddhivinayak; Homaira, Nusrat; Howie, Stephen R C; Jara, Jorge; Jroundi, Imane; Kartasasmita, Cissy B; Khuri-Bulos, Najwa; Kotloff, Karen L; Krishnan, Anand; Libster, Romina; Lopez, Olga; Lucero, Marilla G; Lucion, Florencia; Lupisan, Socorro P; Marcone, Debora N; McCracken, John P; Mejia, Mario; Moisi, Jennifer C; Montgomery, Joel M; Moore, David P; Moraleda, Cinta; Moyes, Jocelyn; Munywoki, Patrick; Mutyara, Kuswandewi; Nicol, Mark P; Nokes, D James; Nymadawa, Pagbajabyn; da Costa Oliveira, Maria Tereza; Oshitani, Histoshi; Pandey, Nitin; Paranhos-Baccalà, Gláucia; Phillips, Lia N; Picot, Valentina Sanchez; Rahman, Mustafizur; Rakoto-Andrianarivelo, Mala; Rasmussen, Zeba A; Rath, Barbara A; Robinson, Annick; Romero, Candice; Russomando, Graciela; Salimi, Vahid; Sawatwong, Pongpun; Scheltema, Nienke; Schweiger, Brunhilde; Scott, J Anthony G; Seidenberg, Phil; Shen, Kunling; Singleton, Rosalyn; Sotomayor, Viviana; Strand, Tor A; Sutanto, Agustinus; Sylla, Mariam; Tapia, Milagritos D; Thamthitiwat, Somsak; Thomas, Elizabeth D; Tokarz, Rafal; Turner, Claudia; Venter, Marietjie; Waicharoen, Sunthareeya; Wang, Jianwei; Watthanaworawit, Wanitda; Yoshida, Lay-Myint; Yu, Hongjie; Zar, Heather J; Campbell, Harry; Nair, Harish

    2017-09-02

    We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. Globally, RSV is a common cause

  8. Evaluation of a novel web-based prior approval application for palivizumab prophylaxis of respiratory syncytial virus in a state Medicaid program.

    Science.gov (United States)

    Lundeen, Kristin; Pfeiffenberger, Trista; Jacobson Vann, Julie; O'Brien, Timothy; Sampson, Charlene; Wegner, Steven

    2013-03-01

    Recent disproportionate increases in use of specialty medications, such as palivizumab (Synagis), compared with steady utilization of traditional medication use, have prompted complex utilization management strategies that require frequent evaluation to facilitate cost-effectiveness while preserving patient access. Clinical criteria utilized by North Carolina (NC) Medicaid for use of palivizumab for respiratory syncytial virus (RSV) prophylaxis are consistent with the most recent guidelines published in the Red Book: Report of the Committee on Infectious Diseases. Prior to the 2011-2012 RSV season, prior approval (PA) requests were submitted by facsimile using the NC Medicaid Synagis PA form. A web-based PA application, which includes automatic approval capability, monthly dose prompts to providers, and a standardized dose projection formula, was developed for the 2011-2012 RSV season. To evaluate the timeliness of palivizumab coverage determination, compliance with palivizumab prophylaxis regimen, and the accuracy of the dose projection formula achieved with this novel web-based PA application for palivizumab prophylaxis in NC Medicaid recipients. A historically controlled retrospective cohort study was conducted in which all palivizumab PA submissions and supporting documentation from the 2010-2011 and 2011-2012 RSV seasons were retrospectively reviewed for date and time of original submission and final coverage determination. Submissions from the 2011-2012 season were also retrospectively reviewed for number of doses approved, number of doses administered, date of administration of each dose, and actual dosage administered. These data were used to evaluate compliance and the projected versus actual beneficiary weight and dose to assess the accuracy of the dose projection formula. Submissions lacking required information were excluded. Time from PA submission to coverage determination was compared between seasons using a 2-sample t-test. The proportion of

  9. Respiratory Syncytial Virus (RSV): Treatment

    Science.gov (United States)

    ... Publications Help Archive Site Map Información en español Employee Information Connect with NIAID Facebook Twitter Linkedin Google+ Youtube Flickr Instagram Pinterest Email Website Policies & Notices ...

  10. Mutation of the elongin C binding domain of human respiratory syncytial virus non-structural protein 1 (NS1 results in degradation of NS1 and attenuation of the virus

    Directory of Open Access Journals (Sweden)

    Headlam Madeleine J

    2011-05-01

    Full Text Available Abstract Background Human respiratory syncytial virus (RSV is an important cause of lower respiratory tract disease in the paediatic population, immunocompromised individuals and the elderly worldwide. However, despite global efforts over the past several decades there are no commercially available vaccines. RSV encodes 2 non-structural proteins, NS1 and NS2, that are type I interferon antagonists. RSV restricts type I interferon signaling and the expression of antiviral genes by degrading STAT2. It has been proposed that NS1 binds to elongin C to form a ubiquitin ligase (E3 complex that targets STAT2 for ubiquitination and proteosomal degradation. Results Here, we have engineered a live recombinant RSV in which the 3 consensus amino acids of the NS1 elongin C binding domain have been replaced with alanine (NS1F-ELCmut. Mutation of this region of NS1 resulted in attenuation of RSV replication in A549 cells to levels similar to that observed when the NS1 gene is completely deleted (ΔNS1. This mutation also resulted in moderate attenuation in Vero cells. Attenuation was correlated to intracellular degradation of the mutated NS1 protein. Time course analysis showed that mutant NS1 protein accumulated in cytoplasmic bodies that contained the lysosomal marker LAMP1. However lack of cleavage of LC3 suggested that autophagy was not involved. Induction of IFN-β mRNA expression also was observed in association with the degradation of NS1 protein and attenuation of viral growth. Conclusions These results indicate that the elongin C binding region of NS1 is crucial for survival of the protein and that disruption of this region results in the degradation of NS1 and restriction of RSV replication.

  11. Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses.

    Science.gov (United States)

    Wang, D; Bayliss, S; Meads, C

    2011-01-01

    Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children. To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection. A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched. Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to

  12. CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs.

    Science.gov (United States)

    Zhang, Lei; Li, Hongyong; Hai, Yan; Yin, Wei; Li, Wenjian; Zheng, Boyang; Du, Xiaomin; Li, Na; Zhang, Zhengzheng; Deng, Yuqing; Zeng, Ruihong; Wei, Lin

    2017-05-15

    Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine-enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross talk between TLR and Notch signaling pathways results in fine-tuning of TLR-triggered innate inflammatory responses. We evaluated the impact of TLR and Notch signaling on ERD in a murine model by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling during FI-RSV immunization. Activation with CpG or deficiency of MyD88-dependent TLR signaling did not alleviate airway inflammation in FI-RSV-immunized mice. Activation or inhibition of Notch signaling with Dll4, one of the Notch ligands, or L685,458 did not suppress FI-RSV-enhanced airway inflammation either. However, the CpG together with L685,458 markedly inhibited FI-RSV-enhanced airway hyperresponsiveness, weight loss, and lung inflammation. Interestingly, CpG plus L685,458 completely inhibited FI-RSV-associated Th17 and Th17-associated proinflammatory chemokine responses in lungs following RSV challenge but not Th1 or Th2, memory responses. In addition, FI-RSV plus CpG plus L685,458 promoted protective CD8 + lung tissue-resident memory (TRM) cells. These results indicate that activation of TLR signaling combined with inhibition of Notch signaling prevent FI-RSV ERD, and the mechanism appears to involve suppressing proinflammatory Th17 memory responses and promoting protective TRM in lungs. IMPORTANCE RSV is the most important cause of lower respiratory tract infections in infants. The FI-RSV-enhanced respiratory disease (ERD) is a major impediment to the development of a safe and

  13. Protection from persistent infection with a bovine viral diarrhea virus (BVDV) type 1b strain by a modified-live vaccine containing BVDV types 1a and 2, infectious bovine rhinotracheitis virus, parainfluenza 3 virus and bovine respiratory syncytial virus.

    Science.gov (United States)

    Xue, Wenzhi; Mattick, Debra; Smith, Linda

    2011-06-24

    Recent studies showed that BVDV-1b subgenotype is dominant in North and South American field BVDV isolates. However, nearly all commercially available BVDV-1 vaccines contain BVDV-1a strains. In order to study the efficacy of BVDV-1a vaccine against BVDV-1b infection, this study was designed to evaluate a modified-live vaccine (MLV) containing BVDV-1a and BVDV-2 strains for its efficacy in prevention of persistent infection of fetuses against BVDV-1b strain, when the heifers were vaccinated prior to breeding. Heifers were vaccinated subcutaneously with a single dose of the MLV and bred four weeks after vaccination. The pregnant heifers were challenged with a non-cytopathic BVDV-1b strain at approximately 80 days of gestation. Vaccinated heifers were protected from clinical disease and viremia caused by the BVDV-1b virus. At approximately 155 days of gestation, the fetuses were harvested and tissue samples of thymus, lungs, spleen, kidney and intestines were collected for virus isolation. BVDV was isolated from 100% of the fetuses in the non-vaccinated control group, and from only one fetus (4.3%) from the vaccinated group. Results demonstrated that the MLV containing BVDV-1a and BVDV-2 strains provided 96% protection from fetal persistent infection caused by the BVDV-1b strain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3' proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity

    NARCIS (Netherlands)

    R.S. Tang (Roderick); J.H. Schickli (Jeanne); M. MacPhail (Mia); F. Fernandes (Fiona); L. Bicha (Leenas); J. Spaete (Joshua); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); R. Spaete (Richard); A.A. Haller (Aurelia)

    2003-01-01

    textabstractA live attenuated bovine parainfluenza virus type 3 (PIV3), harboring the fusion (F) and hemagglutinin-neuraminidase (HN) genes of human PIV3, was used as a virus vector to express surface glycoproteins derived from two human pathogens, human metapneumovirus (hMPV) and respiratory

  15. Hepatitis C Virus-Induced Mitochondrial Dysfunctions

    Directory of Open Access Journals (Sweden)

    Birke Bartosch

    2013-03-01

    Full Text Available Chronic hepatitis C is characterized by metabolic disorders and a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that lead in the long term to hepatocellular carcinoma. Many lines of evidence suggest that mitochondrial dysfunctions, including modification of metabolic fluxes, generation and elimination of oxidative stress, Ca2+ signaling and apoptosis, play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV proteins localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory, probably due to the use of artificial expression and replication systems. In vivo studies are hampered by the fact that innate and adaptive immune responses will overlay mitochondrial dysfunctions induced directly in the hepatocyte by HCV. Thus, the molecular aspects underlying HCV-induced mitochondrial dysfunctions and their roles in viral replication and the associated pathology need yet to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems.

  16. Effects of injectable trace minerals on humoral and cell-mediated immune responses to Bovine viral diarrhea virus, Bovine herpes virus 1 and Bovine respiratory syncytial virus following administration of a modified-live virus vaccine in dairy calves.

    Science.gov (United States)

    Palomares, R A; Hurley, D J; Bittar, J H J; Saliki, J T; Woolums, A R; Moliere, F; Havenga, L J; Norton, N A; Clifton, S J; Sigmund, A B; Barber, C E; Berger, M L; Clark, M J; Fratto, M A

    2016-10-01

    Our objective was to evaluate the effect of an injectable trace mineral (ITM) supplement containing zinc, manganese, selenium, and copper on the humoral and cell mediated immune (CMI) responses to vaccine antigens in dairy calves receiving a modified-live viral (MLV) vaccine containing BVDV, BHV1, PI3V and BRSV. A total of 30 dairy calves (3.5 months of age) were administered a priming dose of the MLV vaccine containing BHV1, BVDV1 & 2, BRSV, PI3V, and an attenuated-live Mannheimia-Pasteurella bacterin subcutaneously (SQ). Calves were randomly assigned to 1 of 2 groups: (1) administration of ITM SQ (ITM, n=15) or (2) injection of sterile saline SQ (Control; n=15). Three weeks later, calves received a booster of the same vaccine combination SQ, and a second administration of ITM, or sterile saline, according to the treatment group. Blood samples were collected on days 0, 7, 14, 21, 28, 42, 56, and 90 post-vaccination for determination of antibody titer, viral recall antigen-induced IFN-γ production, and viral antigen-induced proliferation by peripheral blood mononuclear cells (PBMC). Administration of ITM concurrently with MLV vaccination resulted in higher antibody titers to BVDV1 on day 28 after priming vaccination compared to the control group (P=0.03). Calves treated with ITM showed an earlier enhancement in PBMC proliferation to BVDV1 following vaccination compared to the control group. Proliferation of PBMC after BVDV stimulation tended to be higher on day 14 after priming vaccination in calves treated with ITM than in the control group (P=0.08). Calves that received ITM showed higher PBMC proliferation to BRSV stimulation on day 7 after priming vaccination compared to the control group (P=0.01). Moreover, calves in the ITM group also had an enhanced production IFN-γ by PBMC after stimulation with BRSV on day 21 after priming vaccination compared to day 0 (P<0.01). In conclusion, administration of ITM concurrently with MLV vaccination in dairy calves

  17. Head-to-head comparison of the diagnostic accuracies of BD Veritor™ System RSV and Quidel® Sofia® RSV FIA systems for respiratory syncytial virus (RSV) diagnosis.

    Science.gov (United States)

    Kanwar, Neena; Hassan, Ferdaus; Nguyen, Ashley; Selvarangan, Rangaraj

    2015-04-01

    Respiratory syncytial virus (RSV) is one of the most common causes of severe lower respiratory tract disease among infants and young children. BD Veritor™ System RSV (BD) and Quidel(®) Sofia(®) RSV FIA (QD) are the new generation lateral flow digital immunoassay (DIA) tests with an instrumented read for the qualitative detection of RSV viral antigens. To compare the diagnostic accuracies of BD and QD for RSV detection using fresh nasopharyngeal aspirates and nasopharyngeal swab specimens collected in universal transport media during 2013-2014 respiratory season. The two DIA tests were performed simultaneously on randomly selected specimens on a weekly basis during the RSV season until 200 fresh remnant specimens were enrolled. Real-time RT-PCR assay results were used to compare and evaluate the performance of both RSV DIA assays. Among 200 specimens tested, RSV real-time RT-PCR assay detected RSV in 104 samples, while QD detected 84 samples and BD detected 74 samples as positive. The overall sensitivity for detection of RSV in comparison to PCR was 71.15% (61.3-79.4) for BD and 80.77% (71.6-87.6) for QD system (P=0.36). The specificity was 100% (95.2-100) for both systems. The work flow analysis revealed that the overall specimen processing time was significantly lower for BD as compared with the QD assay. In comparison with the real-time PCR, the QD system showed a higher sensitivity than that of the BD system, but the difference did not reach statistical significance (P=0.36). Both BD and QD systems were found comparable in terms of specificity. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Inflammation and emphysema in cigarette smoke-exposed mice when instilled with poly (I:C) or infected with influenza A or respiratory syncytial viruses

    Science.gov (United States)

    Background: The length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection. However, the extent of inflammatory responses and lung pathologies of mice exposed to CS and infected with influenza A virus (IAV), re...

  19. Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

    Science.gov (United States)

    Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

    2009-08-06

    The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

  20. Human Cytomegalovirus Induces JC Virus DNA Replication in Human Fibroblasts

    Science.gov (United States)

    Heilbronn, Regine; Albrecht, Ingrid; Stephan, Sonja; Burkle, Alexander; Zur Hausen, Harald

    1993-12-01

    JC virus, a human papovavirus, is the causative agent of the demyelinating brain disease progressive multifocal leucoencephalopathy (PML). PML is a rare but fatal disease which develops as a complication of severe immunosuppression. Latent JC virus is harbored by many asymptomatic carriers and is transiently reactivated from the latent state upon immunosuppression. JC virus has a very restricted host range, with human glial cells being the only tissue in which it can replicate at reasonable efficiency. Evidence that latent human cytomegalovirus is harbored in the kidney similar to latent JC virus led to the speculation that during episodes of impaired immunocompetence, cytomegalovirus might serve as helper virus for JC virus replication in otherwise nonpermissive cells. We show here that cytomegalovirus infection indeed leads to considerable JC virus DNA replication in cultured human fibroblasts that are nonpermissive for the replication of JC virus alone. Cytomegalovirus-mediated JC virus replication is dependent on the JC virus origin of replication and T antigen. Ganciclovir-induced inhibition of cytomegalovirus replication is associated with a concomitant inhibition of JC virus replication. These results suggest that reactivation of cytomegalovirus during episodes of immunosuppression might lead to activation of latent JC virus, which would enhance the probability of subsequent PML development. Ganciclovir-induced repression of both cytomegalovirus and JC virus replication may form the rational basis for the development of an approach toward treatment or prevention of PML.

  1. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    International Nuclear Information System (INIS)

    Bates, John T.; Keefer, Christopher J.; Slaughter, James C.; Kulp, Daniel W.; Schief, William R.; Crowe, James E.

    2014-01-01

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K on ) for binding to RSV F protein, while alteration of dissociation rate (K off ) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K on with reduced potency mirrored the effect of increased K on found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K on ) correlated well with the potency of neutralization

  2. Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

    Energy Technology Data Exchange (ETDEWEB)

    Bates, John T. [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Keefer, Christopher J. [The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Slaughter, James C. [The Vanderbilt Vaccine Center, Departments of Biostatistics and Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Kulp, Daniel W. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Schief, William R. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA (United States); Crowe, James E., E-mail: james.crowe@vanderbilt.edu [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2014-04-15

    The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on} with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.

  3. The effect of TIP on pneumovirus-induced pulmonary edema in mice

    NARCIS (Netherlands)

    van den Berg, Elske; Bem, Reinout A.; Bos, Albert P.; Lutter, Rene; van Woensel, Job B. M.

    2014-01-01

    Pulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (RSV)-induced respiratory failure. In this study we determined whether treatment with TIP (AP301), a synthetic cyclic peptide that mimics the lectin-like domain of human TNF, decreases pulmonary edema in a

  4. Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine.

    Science.gov (United States)

    Yang, Chin-Fen; Wang, C Kathy; Malkin, Elissa; Schickli, Jeanne H; Shambaugh, Cindy; Zuo, Fengrong; Galinski, Mark S; Dubovsky, Filip; Tang, Roderick S

    2013-06-10

    MEDI-534 is the first live vectored RSV vaccine candidate to be evaluated in seronegative children. It consists of the bovine parainfluenza virus type 3 (PIV3) genome with substituted human PIV3 F and HN glycoproteins engineered to express RSV F protein. A Phase 1 study of 49 healthy RSV and PIV3 seronegative children 6 to MEDI-534 at 10(6)TCID50, administered at 0, 2 and 4 month intervals, 100% of subjects seroresponded to PIV3, whereas only 50% seroresponded to RSV. To investigate the discordance in seroresponse rates, the RSV F transgene and its flanking non-coding nucleotides were sequenced from shed virus recovered from the nasal washes of 24 MEDI-534-vaccinated children. Eleven out of 24 samples contained no nucleotide changes in the analyzed region. The other 13 samples contained mixtures of variant subpopulations. Fifty-five percent exhibited changes in the transcription termination poly A gene sequences of the upstream bPIV3N gene while 21% had variant subpopulations in the RSV F open reading frame that resulted in pre-mature stop codons. Both types of changes are expected to reduce RSV F expression. Evaluation of the administered vaccine by dual immunofluorescence staining showed ~2.5% variants with low or no RSV F expression while single nucleotide primer extension detected ~1% variation at nucleotide 2045 that resulted in a pre-mature translational termination at codon 85. An association between shedding of variants and lower RSV F serological response was observed but it was not possible to establish a definitive clinical significance due to the small number of subjects in this study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. A Phase 2 randomized, observer-blind, placebo-controlled, dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age.

    Science.gov (United States)

    August, Allison; Glenn, Gregory M; Kpamegan, Eloi; Hickman, Somia P; Jani, Dewal; Lu, Hanxin; Thomas, D Nigel; Wen, Judy; Piedra, Pedro A; Fries, Louis F

    2017-06-27

    Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules. Placebo, or vaccine with 60μg or 120μg RSV F protein and 0.2, 0.4, or 0.8mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18-35years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91. All formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120μg RSV F protein and 0.4mg aluminum, but persistence through 91days was modestly (∼25%) superior following two doses of 60μg RSV F protein and 0.8mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p=0.009 overall) over the Day 0 through 90 period. RSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120μg RSV F and 0.4mg aluminum, which achieved peak immune responses in 14days and sufficient persistence through 91days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686. Copyright © 2017 Novavax. Published by Elsevier Ltd.. All rights reserved.

  6. Expression of the B cell differentiation factor BAFF and chemokine CXCL13 in a murine model of Respiratory Syncytial Virus infection.

    Science.gov (United States)

    Alturaiki, Wael; McFarlane, Amanda J; Rose, Katie; Corkhill, Rachel; McNamara, Paul S; Schwarze, Jürgen; Flanagan, Brian F

    2018-01-26

    Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection. Following infection with A2 strain RSV, the highest RSV N gene expression was observed at day 4 after challenge with virus. In contrast, two peaks of elevated BAFF expression at days 2 and 7 were observed. CXCL13 was significantly elevated at days 1, 2 and 7. CXCL12, CCL19 and CCL21 were expressed within lung tissue from control and RSV challenged animals but no significant difference in expression was found. Immunofluorescence showed BAFF to be present throughout the tissue however CXCL13 expression was localized to cell rich areas probably constituting lymphoid aggregates. Our results define the kinetics of B cell chemoattractant and growth factor expression during RSV infection and indicate an important role for these cytokines in the airway response to RSV infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Oxidative Lung Injury in Virus-Induced Wheezing

    Science.gov (United States)

    2014-05-01

    antioxidant enzyme (AOE) genes in the lung. Thus, we propose a new molecular pathway by which respiratory viruses induce lung inflammation, with implication...AOE) genes in the lung. Thus, we propose a new molecular pathway by which respiratory viruses induce lung inflammation, with implication for novel...model of infection, with significant amelioration of oxidative stress, which is an important pathogenetic component of viral-induced lung disease

  8. Inducible resistance to maize streak virus.

    Science.gov (United States)

    Shepherd, Dionne N; Dugdale, Benjamin; Martin, Darren P; Varsani, Arvind; Lakay, Francisco M; Bezuidenhout, Marion E; Monjane, Adérito L; Thomson, Jennifer A; Dale, James; Rybicki, Edward P

    2014-01-01

    Maize streak virus (MSV), which causes maize streak disease (MSD), is the major viral pathogenic constraint on maize production in Africa. Type member of the Mastrevirus genus in the family Geminiviridae, MSV has a 2.7 kb, single-stranded circular DNA genome encoding a coat protein, movement protein, and the two replication-associated proteins Rep and RepA. While we have previously developed MSV-resistant transgenic maize lines constitutively expressing "dominant negative mutant" versions of the MSV Rep, the only transgenes we could use were those that caused no developmental defects during the regeneration of plants in tissue culture. A better transgene expression system would be an inducible one, where resistance-conferring transgenes are expressed only in MSV-infected cells. However, most known inducible transgene expression systems are hampered by background or "leaky" expression in the absence of the inducer. Here we describe an adaptation of the recently developed INPACT system to express MSV-derived resistance genes in cell culture. Split gene cassette constructs (SGCs) were developed containing three different transgenes in combination with three different promoter sequences. In each SGC, the transgene was split such that it would be translatable only in the presence of an infecting MSV's replication associated protein. We used a quantitative real-time PCR assay to show that one of these SGCs (pSPLITrepIII-Rb-Ubi) inducibly inhibits MSV replication as efficiently as does a constitutively expressed transgene that has previously proven effective in protecting transgenic maize from MSV. In addition, in our cell-culture based assay pSPLITrepIII-Rb-Ubi inhibited replication of diverse MSV strains, and even, albeit to a lesser extent, of a different mastrevirus species. The application of this new technology to MSV resistance in maize could allow a better, more acceptable product.

  9. Inducible resistance to maize streak virus.

    Directory of Open Access Journals (Sweden)

    Dionne N Shepherd

    Full Text Available Maize streak virus (MSV, which causes maize streak disease (MSD, is the major viral pathogenic constraint on maize production in Africa. Type member of the Mastrevirus genus in the family Geminiviridae, MSV has a 2.7 kb, single-stranded circular DNA genome encoding a coat protein, movement protein, and the two replication-associated proteins Rep and RepA. While we have previously developed MSV-resistant transgenic maize lines constitutively expressing "dominant negative mutant" versions of the MSV Rep, the only transgenes we could use were those that caused no developmental defects during the regeneration of plants in tissue culture. A better transgene expression system would be an inducible one, where resistance-conferring transgenes are expressed only in MSV-infected cells. However, most known inducible transgene expression systems are hampered by background or "leaky" expression in the absence of the inducer. Here we describe an adaptation of the recently developed INPACT system to express MSV-derived resistance genes in cell culture. Split gene cassette constructs (SGCs were developed containing three different transgenes in combination with three different promoter sequences. In each SGC, the transgene was split such that it would be translatable only in the presence of an infecting MSV's replication associated protein. We used a quantitative real-time PCR assay to show that one of these SGCs (pSPLITrepIII-Rb-Ubi inducibly inhibits MSV replication as efficiently as does a constitutively expressed transgene that has previously proven effective in protecting transgenic maize from MSV. In addition, in our cell-culture based assay pSPLITrepIII-Rb-Ubi inhibited replication of diverse MSV strains, and even, albeit to a lesser extent, of a different mastrevirus species. The application of this new technology to MSV resistance in maize could allow a better, more acceptable product.

  10. Respiratory syncytial viral infections in young children : risk assessment and prevention

    NARCIS (Netherlands)

    E. Rietveld (Edwin)

    2003-01-01

    textabstractRespiratory syncytial virus is the main cause of lower respiratory tract infections in infants and young children. Although almost all children are infected before the age of two years, less than 2% develop severe disease necessitating hospitalisation. Risk factors for severe RSV

  11. A randomized placebo controlled trial of ibuprofen for respiratory syncytial infection in a bovine model study

    Science.gov (United States)

    Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to ...

  12. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    Full Text Available INTRODUCTION: RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2 ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine. OBJECTIVE: To explore if intranasal (IN immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity. METHODS: We produced RSV-virosomes carrying TLR2 (Pam3CSK4 and/or NOD2 (L18-MDP ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice. RESULTS: Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced

  13. Clinical patterns and seasonal trends in respiratory syncytial virus hospitalizations in São Paulo, Brazil Padrões clínicos e sazonalidade das hospitalizações causadas pelo vírus respiratório sincicial em São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    Sandra E. VIEIRA

    2001-06-01

    Full Text Available The respiratory viruses are recognized as the most frequent lower respiratory tract pathogens for infants and young children in developed countries but less is known for developing populations. The authors conducted a prospective study to evaluate the occurrence, clinical patterns, and seasonal trends of viral infections among hospitalized children with lower respiratory tract disease (Group A. The presence of respiratory viruses in children's nasopharyngeal was assessed at admission in a pediatric ward. Cell cultures and immunofluorescence assays were used for viral identification. Complementary tests included blood and pleural cultures conducted for bacterial investigation. Clinical data and radiological exams were recorded at admission and throughout the hospitalization period. To better evaluate the results, a non- respiratory group of patients (Group B was also constituted for comparison. Starting in February 1995, during a period of 18 months, 414 children were included- 239 in Group A and 175 in Group B. In Group A, 111 children (46.4% had 114 viruses detected while only 5 children (2.9% presented viruses in Group B. Respiratory Syncytial Virus was detected in 100 children from Group A (41.8%, Adenovirus in 11 (4.6%, Influenza A virus in 2 (0.8%, and Parainfluenza virus in one child (0.4%. In Group A, aerobic bacteria were found in 14 cases (5.8%. Respiratory Syncytial Virus was associated to other viruses and/or bacteria in six cases. There were two seasonal trends for Respiratory Syncytial Virus cases, which peaked in May and June. All children affected by the virus were younger than 3 years of age, mostly less than one year old. Episodic diffuse bronchial commitment and/or focal alveolar condensation were the clinical patterns more often associated to Respiratory Syncytial Virus cases. All children from Group A survived. In conclusion, it was observed that Respiratory Syncytial Virus was the most frequent pathogen found in hospitalized

  14. Mechanisms of Virus-Induced Neural Cell Death

    National Research Council Canada - National Science Library

    Tyler, Kenneth

    2002-01-01

    Virtually all known neurotropic viruses are capable of killing infected cells by inducing a specific pattern of cell death known as apoptosis, yet the mechanism by which this occurs and its relevance...

  15. Antiviral effects of bovine interferons on bovine respiratory tract viruses.

    OpenAIRE

    Fulton, R W; Downing, M M; Cummins, J M

    1984-01-01

    The antiviral effects of bovine interferons on the replication of bovine respiratory tract viruses were studied. Bovine turbinate monolayer cultures were treated with bovine interferons and challenged with several bovine herpesvirus 1 strains, bovine viral diarrhea virus, parainfluenza type 3 virus, goat respiratory syncytial virus, bovine respiratory syncytial virus, bovine adenovirus type 7, or vesicular stomatitis virus. Treatment with bovine interferons reduced viral yield for each of the...

  16. A Foxtail mosaic virus Vector for Virus-Induced Gene Silencing in Maize1[OPEN

    Science.gov (United States)

    Mei, Yu; Kernodle, Bliss M.; Hill, John H.

    2016-01-01

    Plant viruses have been widely used as vectors for foreign gene expression and virus-induced gene silencing (VIGS). A limited number of viruses have been developed into viral vectors for the purposes of gene expression or VIGS in monocotyledonous plants, and among these, the tripartite viruses Brome mosaic virus and Cucumber mosaic virus have been shown to induce VIGS in maize (Zea mays). We describe here a new DNA-based VIGS system derived from Foxtail mosaic virus (FoMV), a monopartite virus that is able to establish systemic infection and silencing of endogenous maize genes homologous to gene fragments inserted into the FoMV genome. To demonstrate VIGS applications of this FoMV vector system, four genes, phytoene desaturase (functions in carotenoid biosynthesis), lesion mimic22 (encodes a key enzyme of the porphyrin pathway), iojap (functions in plastid development), and brown midrib3 (caffeic acid O-methyltransferase), were silenced and characterized in the sweet corn line Golden × Bantam. Furthermore, we demonstrate that the FoMV infectious clone establishes systemic infection in maize inbred lines, sorghum (Sorghum bicolor), and green foxtail (Setaria viridis), indicating the potential wide applications of this viral vector system for functional genomics studies in maize and other monocots. PMID:27208311

  17. A Foxtail mosaic virus Vector for Virus-Induced Gene Silencing in Maize.

    Science.gov (United States)

    Mei, Yu; Zhang, Chunquan; Kernodle, Bliss M; Hill, John H; Whitham, Steven A

    2016-06-01

    Plant viruses have been widely used as vectors for foreign gene expression and virus-induced gene silencing (VIGS). A limited number of viruses have been developed into viral vectors for the purposes of gene expression or VIGS in monocotyledonous plants, and among these, the tripartite viruses Brome mosaic virus and Cucumber mosaic virus have been shown to induce VIGS in maize (Zea mays). We describe here a new DNA-based VIGS system derived from Foxtail mosaic virus (FoMV), a monopartite virus that is able to establish systemic infection and silencing of endogenous maize genes homologous to gene fragments inserted into the FoMV genome. To demonstrate VIGS applications of this FoMV vector system, four genes, phytoene desaturase (functions in carotenoid biosynthesis), lesion mimic22 (encodes a key enzyme of the porphyrin pathway), iojap (functions in plastid development), and brown midrib3 (caffeic acid O-methyltransferase), were silenced and characterized in the sweet corn line Golden × Bantam. Furthermore, we demonstrate that the FoMV infectious clone establishes systemic infection in maize inbred lines, sorghum (Sorghum bicolor), and green foxtail (Setaria viridis), indicating the potential wide applications of this viral vector system for functional genomics studies in maize and other monocots. © 2016 American Society of Plant Biologists. All Rights Reserved.

  18. A recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice.

    Science.gov (United States)

    Li, Zhili; Wang, Jigui; Yuan, Daoli; Wang, Shuang; Sun, Jiazeng; Yi, Bao; Hou, Qiang; Mao, Yaping; Liu, Weiquan

    2015-06-01

    Canine distemper virus (CDV) and rabies virus (RV) are two important pathogens of the dog. CDV, a member of the morbillivirus genus, has shown promise as an expression vector. The glycoprotein from RV is a main contributor to protective immunity and capable of eliciting the production of virus-neutralizing antibodies. In this study, we recovered an attenuated strain of canine distemper virus and constructed a recombinant virus, rCDV-RV-G, expressing a modified (R333Q) rabies virus glycoprotein (RV-G) of RV Flury strain LEP. RV-G expression by the recombinant viruses was confirmed. Furthermore, G was proved to be incorporated into the surface of CDV particles. While replication of the recombinant virus was slightly reduced compared with the parental CDV, it stably expressed the RV-G over ten serial passages. Inoculation of mice induced specific neutralizing antibodies against both RV-G and CDV. Therefore, the rCDV-RV-G has the potential as a vaccine that may be used to control rabies virus infection in dogs and other animals.

  19. Usefulness of Ct value in acute respiratory infections caused by respiratory syncytial virus A and B and influenza virus A (H1N1)pdm09, A (H3N2) and B.

    Science.gov (United States)

    Reina, Jordi; Morales, Carmen; Busquets, María; Norte, Cristina

    2017-06-07

    Acute respiratory infections of viral cause are very frequent entities. The difficulty in evaluating the detection of a virus in these entities could be solved by determining the viral load. A prospective study on the mean Ct value (cycle threshold value) detected against RSV-A, RSV-B and influenza A (H1N1)pdm09, A (H3N2) and B viruses in patients of different origin and age was performed. Detection was performed using a commercial molecular amplification (RT-PCR) technique. Different mean Ct values were detected for each virus. In RSV infections, no differences were observed between those caused by RSV-A or RSV-B in children. Depending on the patient's age, the only statistical significance was observed in those included in the 0-4 month groups for RSV-A and this group and the 5-12 months group for RSV-B (higher values). A lower viral load was detected in adult patients than in paediatric patients. In influenza infections, no statistical significance was observed in the mean values detected in patients from the Red Centinela («sentinel network», a Spanish network of doctors aimed at research and surveillance of diseases), those diagnosed in the adult emergency room or in hospital admissions. In the adult patients admitted to the ICU, only a slightly lower mean value was observed in those infected with influenza A (H1N1)pdm09, but without statistical significance. There were no patients admitted to the ICU with influenza B infection. The detection of viral load could be a good tool for the evaluation, monitoring and prognosis of acute viral respiratory infections. With the exception of those caused by RSV, no significant differences were observed in influenza infections except in younger paediatric patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

    2017-04-15

    recombinant rabies viruses carrying only the CDV attachment protein according to the same immunization scheme died. Irrespective of the CDV antigens used, all animals developed protective titers against rabies virus, illustrating that a bivalent rabies virus-based vaccine against CDV induces protective immune responses against both pathogens. Copyright © 2017 American Society for Microbiology.

  1. Zika Virus-Induced Microcephaly and Its Possible Molecular Mechanism.

    Science.gov (United States)

    Faizan, Md Imam; Abdullah, Mohd; Ali, Sher; Naqvi, Irshad H; Ahmed, Anwar; Parveen, Shama

    2016-01-01

    Zika virus is an arthropod-borne re-emerging pathogen associated with the global pandemic of 2015-2016. The devastating effect of Zika viral infection is reflected by its neurological manifestations such as microcephaly in newborns. This scenario evoked our interest to uncover the neurotropic localization, multiplication of the virus, and the mechanism of microcephaly. The present report provides an overview of a possible molecular mechanism of Zika virus-induced microcephaly based on recent publications. Transplacental transmission of Zika viral infection from mother to foetus during the first trimester of pregnancy results in propagation of the virus in human neural progenitor cells (hNPCs), where entry is facilitated by the receptor (AXL protein) leading to the alteration of signalling and immune pathways in host cells. Further modification of the viral-induced TLR3-mediated immune network in the infected hNPCs affects viral replication. Downregulation of neurogenesis and upregulation of apoptosis in hNPCs leads to cell cycle arrest and death of the developing neurons. In addition, it is likely that the environmental, physiological, immunological, and genetic factors that determine in utero transmission of Zika virus are also involved in neurotropism. Despite the global concern regarding the Zika-mediated epidemic, the precise molecular mechanism of neuropathogenesis remains elusive. © 2017 S. Karger AG, Basel.

  2. Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats.

    Science.gov (United States)

    Overbaugh, J; Donahue, P R; Quackenbush, S L; Hoover, E A; Mullins, J I

    1988-02-19

    A replication-defective variant of feline leukemia virus was molecularly cloned directly from infected tissue and found to induce a rapid and fatal immunodeficiency syndrome in cats. Studies with cloned viruses also showed that subtle mutational changes would convert a minimally pathogenic virus into one that would induce an acute form of immunodeficiency. The data suggest that acutely pathogenic viruses may be selected against by current methods for isolation of the human and simian immunodeficiency viruses.

  3. Virus-induced Systemic Vasculitides: New Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Loïc Guillevin

    2004-01-01

    Full Text Available The best therapeutic strategy in virus-induced vasculitides should take into account the etiology of the disease and be adapted to the pathogenesis. The combination of antiviral treatments and plasma exchanges has been proven effective in polyarteritis nodosa (PAN. In human immunodeficiency virus (HIV-related vasculitis this strategy is also effective and does not jeopardize, like cytotoxic agents, the outcome of AIDS. In vasculitis related to HCV-associated cryoglobulinemia, plasma exchanges improve the outcome but the poor effectiveness of antiviral drugs is not able to favor, usually, a definite recovery of the patients and relapses are frequent.

  4. Studies on virus-induced cell fusion. Progress report, August 1, 1977--June 30, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Person, S.

    1978-07-01

    We have previously postulated that wild-type Herpes Simplex Virus type I (HSV-1) infections are characterized by the presence of a fusion factor and a fusion inhibitor activity. The fusion inhibitor presumably is dominant so that a small fraction of cells fuse in a typical wild-type infection. Furthermore, the syn mutants isolated in our laboratory are thought to cause extensive cell fusion because the production of active fusion inhibitor in cell membranes is delayed. If mutations existed that altered both the fusion factor and fusion inhibitor activity then separate viruses containing these two mutations might be able to complement each other, each supplying the defective gene product missing in the other virus. This would produce a wild type and not a syncytial mutant response. Complementation tests between two viruses, tsB5 and syn 20, which are thought to contain defects in the production of active fusion factor and fusion inhibitor activity, respectively, were done. A wild-type response was observed indicating that the mutations affecting fusion were in two separate genes.

  5. Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Ravn, Henrik; Kristensen, Kim

    2008-01-01

    Cohort, we selected a subcohort of 459 randomly selected children, 408 children with RSV hospitalization, 408 children with recurrent wheeze, and all 289 children who experienced both RSV hospitalization and recurrent wheeze. The influence of cord blood RSV neutralizing antibodies was examined...

  6. Virus-Induced Gene Silencing in Maize with a Foxtail mosaic virus Vector.

    Science.gov (United States)

    Mei, Yu; Whitham, Steven A

    2018-01-01

    Virus-induced gene silencing (VIGS) is a powerful technology for rapidly and transiently knocking down the expression of plant genes to study their functions. A VIGS vector for maize derived from Foxtail mosaic virus (FoMV), a positive-sense single-stranded RNA virus, was recently developed. A cloning site created near the 3' end of the FoMV genome enables insertion of 200-400 nucleotide fragments of maize genes targeted for silencing. The recombinant FoMV clones are inoculated into leaves of maize seedlings by biolistic particle delivery, and silencing is typically observed within 2 weeks after inoculation. This chapter provides a protocol for constructing FoMV VIGS clones and inoculating them into maize seedlings.

  7. Astrocytic infection in canine distemper virus-induced demyelination.

    Science.gov (United States)

    Mutinelli, F; Vandevelde, M; Griot, C; Richard, A

    1989-01-01

    Acute canine distemper virus (CDV)-induced demyelinating lesions were examined with double-labelling immunocytochemistry simultaneously demonstrating CDV antigen and glial fibrillary acidid protein (GFAP) as marker for astrocytes. It was shown that 64% of all astrocytes within the demyelinating lesions were infected and that 95% of all infected cells counted in the lesions were astrocytes. These results suggest that the astrocyte is the main target for CDV and that astroglial infection may play an important role in the mechanism of demyelination.

  8. Unit membrane parameters of electrically syncytial tissues.

    Science.gov (United States)

    Levin, D N

    1981-07-01

    A change in the holding voltage, exposure to channel-blocking agents, and similar interventions will induce changes in the membrane properties of electrically syncytial tissues. The altered membrane characteristics will produce changes in the input resistance (RIN) and the phase angle (phi) of the complex admittance of the whole preparation. Exact geometry-independent formulas are derived that give the intervention-induced changes in the membrane capacitance and conductance in terms of the measured changes in RIN and phi. The formulas automatically account for the effects of extracellular resistance in tissues such as skeletal muscle fibers, cardiac Purkinje fibers, and small cardiac "aggregates." The size, shape, and resistance of the extracellular space may be arbitrary and need not be measured. The surface (invaginated) membranes, which face the bath (extracellular space), are assumed to be characterized by an RC circuit with specific capacity Cme (Cmi) and specific conductivity gme (gmi). It is assumed that the intracellular voltage gradient between the electrodes and the membranes is negligible or reliably calculable. The intervention is assumed to leave the geometry and resistivity of the extracellular space unchanged. Under these circumstances the intervention-induced changes in Cme, Cmi, gme, and gmi are determined exactly in terms of the corresponding changes in RIN and certain frequency domain integrals over phi. The technique is illustrated by synthetic data for RIN and phi generated by the "disk" model of a skeletal muscle fiber in which Cme and Cmi depend upon holding voltage. The corresponding voltage dependence of RIN and phi is successfully "inverted" to expose the underlying voltage dependence of Cme and Cmi. These computations suggest that the formulas for Cme and Cmi will be useful in realistic situations, since they are not too sensitive to experimental error in the data for RIN and phi. This method makes it possible to detect voltage

  9. Zika Virus-Induced Antibody Response Enhances Dengue Virus Serotype 2 Replication In Vitro.

    Science.gov (United States)

    Kawiecki, Anna B; Christofferson, Rebecca C

    2016-11-01

    Zika virus has emerged in the Americas, where dengue virus is endemic. Among the 4 serotypes of dengue virus, antibody-dependent enhancement is thought to enhance viral replication and disease severity. Reports suggest that anti-dengue virus antibody may enhance Zika virus replication. We investigated whether Zika virus antibodies enhance dengue virus replication, by exposing C57Bl/6 mice to Zika virus. Polyclonal serum was verified for strong Zika virus-neutralizing, dengue virus-subneutralizing capacity. Then we determined the enhancement capabilities of Zika virus-immune serum for dengue virus in vitro. We showed that Zika virus antibodies have the ability to enhance dengue virus infections, which is important, because in many Zika virus-affected areas, dengue virus is expected to remain endemic. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  10. Molecular cloning of osteoma-inducing replication-competent murine leukemia viruses from the RFB osteoma virus stock

    DEFF Research Database (Denmark)

    Pedersen, Lene; Behnisch, Werner; Schmidt, Jörg

    1992-01-01

    We report the molecular cloning of two replication-competent osteoma-inducing murine leukemia viruses from the RFB osteoma virus stock (M. P. Finkel, C. A. Reilly, Jr., B. O. Biskis, and I. L. Greco, p. 353-366, in C. H. G. Price and F. G. M. Ross, ed., Bone--Certain Aspects of Neoplasia, 1973...

  11. Virus-induced gene silencing in diverse maize lines using the Brome Mosaic virus-based silencing vector

    Science.gov (United States)

    Virus-induced gene silencing (VIGS) is a widely used tool for gene function studies in many plant species, though its use in monocots has been limited. Using a Brome mosaic virus (BMV) vector designed to silence the maize phytoene desaturase gene, a genetically diverse set of maize inbred lines was ...

  12. Virus como inductores de neoplasias cutáneas Viruses as agents inducing cutaneous neoplasms

    Directory of Open Access Journals (Sweden)

    Francisco Bravo Puccio

    2013-03-01

    Full Text Available El rol oncogénico de los virus en las neoplasias cutáneas es conocido por el hombre desde hace más de un siglo, cuando se atribuía el origen de la verruga vulgar al virus papiloma humano (VPH. En la actualidad, las neoplasias inducidas por virus pueden agruparse en tumores sólidos y procesos linfoproliferativos. Destacan entre los primeros el VPH, del cual ahora conocemos numerosos serotipos, cada uno vinculado a una neoplasia específica, el herpesvirus humano tipo 8 que produce el sarcoma de Kaposi y el poliomavirus vinculado al carcinoma de Merkel. Entre los procesos linfoproliferativos debemos mencionar al virus linfotrópico de células T humanas tipo 1 (HTLV-1 responsable de los linfomas de células T, en los cuales el compromiso cutáneo es inespecífico, con un amplio espectro de presentaciones clínicas y, que por consiguiente, plantean un reto para el diagnóstico diferencial. En este grupo también se encuentra el virus Epstein Barr vinculado a los linfomas nasales de Células NK/T y a los linfomas tipo Hidroa, de reciente descripción. En esta era en la que lo genético y lo molecular priman en las investigaciones en cáncer, no podemos dejar de lado el concepto de neoplasia como resultado de la infección por un agente viral, lo que abre una nueva veta de posibilidades de tratamiento anticanceroso basado en medicamentos antiviralesThe oncogenic role of viruses in cutaneous neoplasms has been known by humankind for more than a century, when the origin of the common wart, or verruca vulgaris, was attributed to the human papilloma virus (HPV. Currently, virus-induced cutaneous neoplasms may be grouped into solid tumors and lymphoproliferative disorders. HPV, from which various serotypes are now known, each being linked to a specific neoplasm, the human herpes virus type 8 producing Kaposi sarcoma, and the Merkel cell polyomavirus, highlight among the first group. Regarding the lymphoproliferative disorders, we should mention the

  13. West nile virus encephalitis induced opsoclonus-myoclonus syndrome.

    Science.gov (United States)

    Cooper, Chad J; Said, Sarmad

    2014-04-22

    West Nile virus (WNV) is an arthropod borne neurotropic single stranded RNA flavivirus with syndrome (OMS) induced by the WNV meningoencephalitis. She then received five consecutive days of plasmapheresis with a significant improvement in her neurological status. Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder associated with chaotic multidirectional eye movements, myoclonus and less frequently cerebellar ataxia. OMS affects as few as 1 in 10,000,000 people per year. The pathogenesis is not fully understood with the majority of cases of opsoclonus-myoclonus syndrome being idiopathic. According to current medical literature there have only been two previous case reports of opsoclonus myoclonus syndrome associated with WNV encephalitis.

  14. Lower respiratory tract infection caused by respiratory syncytial virus in infants: the role played by specific antibodies Infecção por virus sincicial respiratório: o papel dos anticorpos séricos específicos

    Directory of Open Access Journals (Sweden)

    Sandra E. Vieira

    2007-01-01

    Full Text Available INTRODUCTION: Respiratory syncytial virus (RSV is a major etiological agent of lower respiratory tract infection in infants. Genotypes of this virus and the role of the infants' serum antibodies have yet to be fully clarified. This knowledge is important for the development of effective therapeutic and prophylactic measures. OBJECTIVES: To evaluate the types and genotypes of RSV causing respiratory tract infection in infants, to analyze the association of subtype-specific serum antibodies with the occurrence of infection and to evaluate the presence of subtype-specific antibodies in the infants' mothers and their association with the profile of the childrens' serum antibodies. METHODS: This was a prospective study on infants hospitalized with respiratory infection. Nasopharyngeal secretions were collected for viral investigation using indirect immunofluorescence and viral culture and blood was collected to test for antibodies using the Luminex Multiplex system. RESULTS: 192 infants were evaluated, with 60.9% having RSV (73.5%- A and 20.5% B. Six genotypes of the virus were identified: A5, A2, B3, B5, A7 and B4. The seroprevalence of the subtype-specific serum antibodies was high. The presence and levels of subtype-specific antibodies were similar, irrespective of the presence of infection or the viral type or genotype. The mothers' antibody profiles were similar to their infants'. CONCLUSIONS: Although the prevalence of subtype-specific antibodies was elevated, these antibodies did not provide protection independently of virus type/genotype. The similarity in the profiles of subtype-specific antibodies presented by the mothers and their children was consistent with transplacental passage.INTRODUÇÃO: O vírus sincicial respiratório é um dos principais agentes etiológicos das infecções do aparelho respiratório inferior em lactentes. Os genótipos deste vírus e o papel dos anticorpos séricos ainda não estão esclarecidos. Este

  15. Identification of virus isolates inducing mosaic of sugarcane in ...

    African Journals Online (AJOL)

    Sugarcane mosaic disease caused by sugarcane mosaic virus (SCMV), Johnsongrass mosaic virus (JGMV), maize dwarf mosaic virus (MDMV) and sorghum mosaic Virus (SrMV) is an economically important viral disease of sugarcane worldwide. Field survey was conducted to assess the presence of the viruses involve in ...

  16. Characterization of Influenza Virus-Induced Leukocyte Adherence to Human Umbilical Vein Endothelial Cell Monolayers

    Science.gov (United States)

    1993-07-01

    with other viruses. HL-60 cell adherence to endothelial cell virus type A, which did not infect human venous or bovine monolayers was modulated by...LEUCOCYTE ADHERENC:E TO [NDOTIIELIL (FS1% A. B reawsd on parainfluenza virus-infected airway epithelial Poiy-iiysine Codled IPLC) Wells PLC.Wells cells...an antibody against ICAN1- I has no significant effect PLC Wells Virus on parainfluenza -induced neutrophil adherence (58). In 25 *HSV-intected HUVEC

  17. Comparison of single vaccination versus revaccination with a modified-live virus vaccine containing bovine herpesvirus-1, bovine viral diarrhea virus (types 1a and 2a), parainfluenza type 3 virus, and bovine respiratory syncytial virus in the prevention of bovine respiratory disease in cattle.

    Science.gov (United States)

    Step, Douglas L; Krehbiel, Clinton R; Burciaga-Robles, Luis O; Holland, Ben P; Fulton, Robert W; Confer, Anthony W; Bechtol, David T; Brister, David L; Hutcheson, John P; Newcomb, Harold L

    2009-09-01

    Objective-To compare effects of administration of a modified-live respiratory virus vaccine once with administration of the same vaccine twice on the health and performance of cattle. Design-Randomized, controlled trial. Animals-612 mixed-breed male cattle with unknown health histories. Procedures-Cattle were randomly assigned to 1 of 2 treatment groups (single vaccination treatment group [SVAC group] vs revaccination treatment group [REVAC group]) during the preconditioning phase of production. All cattle were given a modified-live respiratory virus vaccine. Eleven days later, REVAC group cattle received a second injection of the same vaccine. During the finishing phase of production, cattle from each treatment group were either vaccinated a third time with the modified-live respiratory virus vaccine or given no vaccine. Health observations were performed daily. Blood and performance variables were measured throughout the experiment. Results-During preconditioning, no significant differences were observed in performance or antibody production between groups. Morbidity rate from bovine respiratory disease was lower for SVAC group cattle; however, days to first treatment for bovine respiratory disease were not different between groups. No significant differences in body weights, daily gains, or dry-matter intake between groups were observed during the finishing phase. Revaccination treatment group cattle had improved feed efficiency regardless of vaccination protocol in the finishing phase. Conclusions and Clinical Relevance-Vaccination once with a modified-live respiratory virus vaccine was as efficacious as vaccination twice in the prevention of bovine respiratory disease of high-risk cattle, although feed efficiency was improved in REVAC group cattle during the finishing period.

  18. Concentrações de interleucina-2 na secreção nasofaríngea de crianças com bronquiolite viral aguda pelo vírus respiratório sincicial Concentrations of interleukin-2 in the nasopharyngeal secretion of children with acute respiratory syncytial virus bronchiolitis

    Directory of Open Access Journals (Sweden)

    Katia M. Giugno

    2004-08-01

    Full Text Available OBJETIVO: Avaliar as concentrações de interleucina-2 (IL-2 na secreção nasofaríngea de crianças (0-24 meses acometidas de bronquiolite viral aguda pelo vírus respiratório sincicial nas primeiras 12 horas de hospitalização e correlacionar os níveis encontrados com a gravidade da doença. MÉTODOS: Estudo prospectivo com amostragem seqüencial realizado no período de junho a agosto de 1999. Foram incluídos 62 pacientes previamente hígidos, internados com diagnóstico de bronquiolite viral aguda caracterizado por pródromos recentes de coriza e/ou obstrução nasal que evoluíram com pelo menos dois dos seguintes sinais: disfunção respiratória, taquipnéia, sibilos ou crepitações. Todos os pacientes tiveram a presença de vírus respiratório sincicial detectada no aspirado nasofaríngeo. As amostras de secreção nasofaríngea foram obtidas nas primeiras 12 horas de hospitalização. As dosagens de IL-2 foram realizadas por ensaio imunoenzimático. A gravidade da doença foi avaliada por: medida da saturação de oxigênio da hemoglobina por oximetria de pulso, sistema de escore clínico modificado, tempo de uso de oxigênio, tempo de hospitalização e necessidade de ventilação mecânica, sendo estas variáveis comparadas em relação às medianas de IL-2 através dos testes de Spearman e Kruskal-Wallis e, para a análise categorizada da interleucina, através do teste de qui-quadrado. RESULTADOS: A mediana de idade dos pacientes foi 2,2 (1,3-4 meses. O sexo masculino foi observado em 54% dos casos. Saturação de oxigênio da hemoglobina por oximetria de pulso na hospitalização foi OBJECTIVE: To assess interleukin-2 concentrations in nasopharyngeal secretion of children (0-24 months with acute respiratory syncytial virus bronchiolitis, within the first 12 hours of hospital admission, and compare the levels of IL-2 with the severity of the illness. METHODS: Prospective study performed between June and August 1999. The study

  19. Nonclinical phenotypic and genotypic analyses of a Phase 1 pediatric respiratory syncytial virus vaccine candidate MEDI-559 (rA2cp248/404/1030ΔSH) at permissive and non-permissive temperatures.

    Science.gov (United States)

    Schickli, Jeanne H; Kaur, Jasmine; Tang, Roderick S

    2012-10-01

    MEDI-559 is a recombinant live attenuated intranasal RSV vaccine candidate currently being evaluated in 5 to MEDI-559 and the previously tested rA2cp248/404/1030ΔSH both have 5 cold-passaged mutations, 3 temperature sensitive (ts) markers designated 248, 404, and 1030, and deletion of the SH gene that collectively contribute to their attenuation and temperature sensitive growth phenotypes. However, MEDI-559 differs from rA2cp248/404/1030ΔSH by 39 silent nucleotide substitutions. Nevertheless, these viruses have comparable in vitro and in vivo phenotypes. Temperature sensitivity is monitored by the efficiency of plaque formation at elevated temperatures. The efficiency of plaque formation of MEDI-559 is reduced by ≥ 100-fold at 35 ° C and by ≥ 1000 fold at 37 °C compared to 32 °C. Passaging of MEDI-559 at temperatures up to 37 °C resulted in generation of temperature sensitive intermediate (tsi) viruses. The most frequent change was a reversion to wildtype tyrosine at the 1030 ts site followed by a less frequently observed leucine to non-wildtype serine substitution at the 248 ts site. One tsi virus had changes at both the 248 and 1030 ts sites and another tsi virus that had maintained all of the 248, 404 and 1030 ts sites had two novel changes (Asp158Gly and Ser1313Cys) in the polymerase (L) gene. Asp158Gly and Ser1313Cys singly or in combination in the MEDI-559 genetic background were confirmed to result in a tsi growth phenotype. All the tsi viruses have small plaque phenotypes and are highly attenuated in the lungs of cotton rats. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. O polietilenoglicol aumenta a penetração do vírus da diarréia viral bovina, do vírus da estomatite vesicular e do vírus sincicial respiratório bovino em células de cultivo Polyethylene glycol increases the penetration of bovine viral diarrhea virus, vesicular stomatitis virus and bovine respiratory syncytial virus in cultured cells

    Directory of Open Access Journals (Sweden)

    Renata Dezengrini

    2009-06-01

    bovine enveloped viruses in culture cells. Penetration efficiency was measured by counting the number of viral plaques produced in bovine kidney cells (MDBK. The addition of 5% PEG (molecular weight 6.000 to the viral inoculum containing 100 TCID50 mL-1 (tissue culture median infectious dosis of each virus, during adsorption for 2h at 37°C, resulted in a significant increase in the number of plaques for bovine viral diarrhea virus (BVDV (increase of 3.4-fold, vesicular stomatitis virus (VSV (2.2-fold and bovine respiratory syncytial virus (BRSV (1.5-fold. The addition of 5% PEG to the inoculum of bovine herpesviruses 1, 2 and 5 (BoHV-1, BoHV-2 and BoHV-5 did not increase the number of viral plaques. On the other hand, PEG produced a reduction in the number of plaques by bovine parainfluenza virus (bPI-3V (1.4-fold. Furthermore, the addition of 5% PEG produced a 10- to 1000-fold increase in the sensitivity of BVDV detection in the serum of three persistently infected calves; and doubled the sensitivity of detection of BRSV in nasal secretions of two experimentally infected sheep. These results demonstrate that PEG enhances the efficiency of infection by BVDV, VSV and BRSV in cultured bovine cells and therefore may be used to increase the sensitivity of virus detection in clinical samples (viral isolation, and/or to increase virus titers in cell cultures.

  1. Heterosubtypic cross-protection induced by whole inactivated influenza virus vaccine in mice : Influence of the route of vaccine administration

    NARCIS (Netherlands)

    Budimir, Natalija; de Haan, Aalzen; Meijerhof, Tjarko; Gostick, Emma; Price, David A.; Huckriede, Anke; Wilschut, Jan

    2013-01-01

    Background Development of influenza vaccines capable of inducing broad protection against different virus subtypes is necessary given the ever-changing viral genetic landscape. Previously, we showed that vaccination with whole inactivated virus (WIV) induces heterosubtypic protection against lethal

  2. Release of Dengue Virus Genome Induced by a Peptide Inhibitor

    OpenAIRE

    Lok, Shee-Mei; Costin, Joshua M.; Hrobowski, Yancey M.; Hoffmann, Andrew R.; Rowe, Dawne K.; Kukkaro, Petra; Holdaway, Heather; Chipman, Paul; Fontaine, Krystal A.; Holbrook, Michael R.; Garry, Robert F.; Kostyuchenko, Victor; Wimley, William C.; Isern, Sharon; Rossmann, Michael G.

    2012-01-01

    Dengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. The mimetic peptide, DN59, consists of residues corresponding to the membrane interacting, amphipathic stem region of the dengue virus envelope (E) glycoprotein. This peptide is inhibitory to all four serotypes of dengue virus, as well as other flaviviruses. Cryo-electron microscopy image reconstruction of dengue virus particles incubated with DN59 showed that the virus particles w...

  3. The DNA Damage Response Induced by Infection with Human Cytomegalovirus and Other Viruses

    Science.gov (United States)

    E, Xiaofei; Kowalik, Timothy F.

    2014-01-01

    Viruses use different strategies to overcome the host defense system. Recent studies have shown that viruses can induce DNA damage response (DDR). Many of these viruses use DDR signaling to benefit their replication, while other viruses block or inactivate DDR signaling. This review focuses on the effects of DDR and DNA repair on human cytomegalovirus (HCMV) replication. Here, we review the DDR induced by HCMV infection and its similarities and differences to DDR induced by other viruses. As DDR signaling pathways are critical for the replication of many viruses, blocking these pathways may represent novel therapeutic opportunities for the treatment of certain infectious diseases. Lastly, future perspectives in the field are discussed. PMID:24859341

  4. Temperature effects on vaccine induced immunity to viruses in fish

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lorenzen, Ellen; Rasmussen, Jesper Skou

    a problem in terms of inducing a protective immune response by vaccination in aquaculture, since it is often desirable to vaccinate fish during autumn, winter, or spring. In experimental vaccination trials with rainbow trout (Oncorhynchus mykiss) using a DNA-vaccine encoding the viral glycoprotein of viral...... haemorrhagic septicaemia virus (VHSV), non-specific as well as specific immune mechanisms seemed to be delayed at low temperature. At five weeks post vaccination fish kept at 5C had no detectable response of neutralising antibodies while two thirds of the fish kept at 15C had sero-converted. While protective...... immunity was still established at both temperatures, specificity analysis suggested that protection at the lower temperature was mainly due to non-specific innate antiviral mechanisms, which appeared to last longer at low temperature. This was presumably related to a prolonged persistence of the vaccine...

  5. cDNA libraries for virus-induced gene silencing.

    Science.gov (United States)

    Todd, Andrea T; Liu, Enwu; Page, Jonathan E

    2010-01-01

    Virus-induced gene silencing (VIGS) exploits endogenous plant antiviral defense mechanisms to posttranscriptionally silence the expression of targeted plant genes. VIGS is quick and relatively easy to perform and therefore serves as a powerful tool for high-throughput functional genomics in plants. Combined with the use of subtractive cDNA libraries for generating a collection of VIGS-ready cDNA inserts, VIGS can be utilized to screen a large number of genes to determine phenotypes resulting from the knockdown/knockout of gene function. Taking into account the optimal insert design for VIGS, we describe a methodology for producing VIGS-ready cDNA libraries enriched for inserts relevant to the biological process of interest.

  6. Highly efficient virus-induced gene silencing in apple and soybean by apple latent spherical virus vector and biolistic inoculation.

    Science.gov (United States)

    Yamagishi, Noriko; Yoshikawa, Nobuyuki

    2013-01-01

    Virus-induced gene silencing (VIGS) is an effective tool for the analysis of the gene function in plants within a short time. However, in woody fruit tree like apple, some of Solanum crops, and soybean, it is generally difficult to inoculate virus vector by conventional inoculation methods. Here, we show efficient VIGS in apple and soybean by Apple latent spherical virus (ALSV) vector and biolistic inoculation. The plants inoculated with ALSV vectors by particle bombardment showed uniform silenced phenotypes of target genes within 2-3 weeks post inoculation.

  7. Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model.

    Science.gov (United States)

    Ermler, Megan E; Kirkpatrick, Ericka; Sun, Weina; Hai, Rong; Amanat, Fatima; Chromikova, Veronika; Palese, Peter; Krammer, Florian

    2017-06-15

    Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed. Copyright © 2017 American Society for Microbiology.

  8. Serological and genetic characterisation of bovine respiratory syncytial virus (BRSV) indicates that Danish isolates belong to the intermediate subgroup: no evidence of a selective effect on the variability of G protein nucleotide sequence by prior cell culture adaption and passages in cell culture

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Uttenthal, Åse; Arctander, P.

    1998-01-01

    , respectively. Phylogenetic analysis showed that the Danish isolates formed three lineages within a separate branch of the phylogenetic tree. Nevertheless, the Danish isolates were closely related to the 220-69Bel isolate, the prototype of the intermediate antigenic subgroup. The sequencing of the extracellular...... part of the G gene of additional 11 field BRSV viruses, processed directly from lung samples without prior adaption to cell culture growth. revealed sequence variabilities in the range obtained with the propagated virus. In addition, several passages in cell culture and in calves had no major impact...... on the nucleotide sequence of the G protein. These findings indicated that the previously established variabilities of the G protein of RS virus isolates were not attributable to mutations induced during the propagation of the virus. The reactivity of the Danish isolates with G protein-specific MAbs were similar...

  9. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication.

    Science.gov (United States)

    Wang, Gefei; Li, Rui; Jiang, Zhiwu; Gu, Liming; Chen, Yanxia; Dai, Jianping; Li, Kangsheng

    2016-01-01

    Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  10. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    Directory of Open Access Journals (Sweden)

    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  11. Mechanisms of pathogenesis induced by bovine leukemia virus (BLV as a model for human T-cell leukemia virus (HTLV

    Directory of Open Access Journals (Sweden)

    Yoko eAida

    2013-11-01

    Full Text Available Bovine leukemia virus (BLV and human T-cell leukemia virus type 1 (HTLV-1 make up a unique retrovirus family. Both viruses induce chronic lymphoproliferative diseases with BLV affecting the B-cell lineage and HTLV-1 affecting the T-cell lineage. The pathologies of BLV- and HTLV-induced infections are notably similar, with an absence of chronic viraemia and a long latency period. These viruses encode at least two regulatory proteins, namely, Tax and Rex, in the pX region located between the env gene and the 3’ long terminal repeat. The Tax protein is a key contributor to the oncogenic potential of the virus, and is also the key protein involved in viral replication. However, BLV infection is not sufficient for leukemogenesis, and additional events such as gene mutations must take place. In this review, we first summarize the similarities between the two viruses in terms of genomic organization, virology and pathology. We then describe the current knowledge of the BLV model, which may also be relevant for the understanding of leukemogenesis caused by HTLV-1. In addition, we address our improved understanding of Tax functions through the newly identified BLV Tax mutants, which have a substitution between amino acids 240 and 265.

  12. Virus Innexins induce alterations in insect cell and tissue function.

    Science.gov (United States)

    Hasegawa, Daniel K; Erickson, Stephanie L; Hersh, Bradley M; Turnbull, Matthew W

    2017-04-01

    Polydnaviruses are dsDNA viruses that induce immune and developmental alterations in their caterpillar hosts. Characterization of polydnavirus gene families and family members is necessary to understand mechanisms of pathology and evolution of these viruses, and may aid to elucidate the role of host homologues if present. For example, the polydnavirus vinnexin gene family encodes homologues of insect gap junction genes (innexins) that are expressed in host immune cells (hemocytes). While the roles of Innexin proteins and gap junctions in insect immunity are largely unclear, we previously demonstrated that Vinnexins form functional gap junctions and alter the junctional characteristics of a host Innexin when co-expressed in paired Xenopus oocytes. Here, we test the effect of ectopic vinnexin expression on host cell physiology using both a lepidopteran cell culture model and a dipteran whole organism model. Vinnexin expression in the cell culture system resulted in gene-specific alterations in cell morphology and a slight, but non-statistically significant, reduction in gap junction activity as measured by dye transfer, while ectopic expression of a lepidopteran innexin2 gene led to morphological alterations and increase in gap junction activity. Global ectopic expression in the model dipteran, Drosophila melanogaster, of one vinnexin (vinnexinG) or D. melanogaster innexin2 (Dm-inx2) resulted in embryonic lethality, while expression of the other vinnexin genes had no effect. Furthermore, ectopic expression of vinnexinG, but not other vinnexin genes or Dm-inx2, in D. melanogaster larval gut resulted in developmental arrest in the pupal stage. These data indicate the vinnexins likely have gene-specific roles in host manipulation. They also support the use of Drosophila in further analysis of the role of Vinnexins and other polydnavirus genes in modifying host physiological processes. Finally, our findings suggest the vinnexin genes may be useful to perturb and

  13. Virus-Induced Gene Silencing as a Tool to Study Tomato Fruit Biochemistry.

    Science.gov (United States)

    Fantini, Elio; Giuliano, Giovanni

    2016-01-01

    Virus-Induced Gene Silencing (VIGS) is an excellent reverse genetic tool for the study of gene function in plants, based on virus infection. In this chapter, we describe a high-throughput approach based on VIGS for the study of tomato fruit biochemistry. It comprises the selection of the sequence for silencing using bioinformatics tools, the cloning of the fragment in the Tobacco Rattle Virus (TRV), and the agroinfiltration of tomato fruits mediated by Agrobacterium tumefaciens.

  14. Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila.

    Science.gov (United States)

    Kemp, Cordula; Mueller, Stefanie; Goto, Akira; Barbier, Vincent; Paro, Simona; Bonnay, François; Dostert, Catherine; Troxler, Laurent; Hetru, Charles; Meignin, Carine; Pfeffer, Sébastien; Hoffmann, Jules A; Imler, Jean-Luc

    2013-01-15

    The fruit fly Drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. The response of Drosophila to virus infections remains poorly characterized and appears to involve two facets. On the one hand, RNA interference involves the recognition and processing of dsRNA into small interfering RNAs by the host RNase Dicer-2 (Dcr-2), whereas, on the other hand, an inducible response controlled by the evolutionarily conserved JAK-STAT pathway contributes to the antiviral host defense. To clarify the contribution of the small interfering RNA and JAK-STAT pathways to the control of viral infections, we have compared the resistance of flies wild-type and mutant for Dcr-2 or the JAK kinase Hopscotch to infections by seven RNA or DNA viruses belonging to different families. Our results reveal a unique susceptibility of hop mutant flies to infection by Drosophila C virus and cricket paralysis virus, two members of the Dicistroviridae family, which contrasts with the susceptibility of Dcr-2 mutant flies to many viruses, including the DNA virus invertebrate iridescent virus 6. Genome-wide microarray analysis confirmed that different sets of genes were induced following infection by Drosophila C virus or by two unrelated RNA viruses, Flock House virus and Sindbis virus. Overall, our data reveal that RNA interference is an efficient antiviral mechanism, operating against a large range of viruses, including a DNA virus. By contrast, the antiviral contribution of the JAK-STAT pathway appears to be virus specific.

  15. Circulating intercellular adhesion molecule-1 (ICAM-1) as an early and sensitive marker for virus-induced T cell activation

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Johansen, J; Marker, O

    1995-01-01

    The effect of systemic virus infection on the level of circulating ICAM-1 (cICAM-1) in serum, and the role of virus-activated T cells in this context, were studied using the murine lymphocytic choriomeningitis virus infection as primary model system. A marked virus-induced elevation in cICAM-1...

  16. Virus-induced gene silencing and Agrobacterium tumefaciens-mediated transient expression in Nicotiana tabacum

    NARCIS (Netherlands)

    Zhang, Z.; Thomma, B.P.H.J.

    2014-01-01

    Virus-induced gene silencing (VIGS) is a rapid method for transient silencing of plant genes. In this chapter, we describe the methodology for Tobacco rattle virus (TRV)-based VIGS in Nicotiana tabacum. In combination with subsequent co-expression of the tomato immune receptor Ve1 and the

  17. Protocol: using virus-induced gene silencing to study the arbuscular mycorrhizal symbiosis in Pisum sativum

    DEFF Research Database (Denmark)

    Grønlund, Mette; Olsen, Anne; Johansen, Elisabeth

    2010-01-01

    Virus-induced gene silencing (VIGS) is an alternative reverse genetics tool for silencing of genes in some plants, which are difficult to transform. The pea early-browning virus (PEBV) has been developed as a VIGS vector and used in pea for functional analysis of several genes. However, the avail...

  18. Reversible acid-induced inactivation of the membrane fusion protein of Semliki Forest virus

    NARCIS (Netherlands)

    Waarts, BL; Smit, JM; Aneke, OJC; McInerney, GM; Liljestrom, P; Bittman, R; Wilschut, J

    Previously, it has been shown that the exposure of Semliki Forest virus (SFV) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. In the present study, incubation of SFV at low pH followed by a specific

  19. Construction of adenoviral vectors expressing F and G glycoproteins of human respiratory syncytial virus (HRSV Construção de vetores adenovirais expressando as glicoproteínas F e G de vírus respiratório sincicial humano (HRSV

    Directory of Open Access Journals (Sweden)

    Ithana Monteiro Kosaka

    2004-06-01

    Full Text Available Human Respiratory Syncytial Virus (HRSV was first characterized in 1957 and has since been recognized as the most common viral cause of severe respiratory tract infection in young infants worldwide. Despite many years of research there is still no effective treatment or any immediate prospect of a vaccine. The HRSV genome is composed of single stranded negative sense RNA and the virion consists of a nucleocapsid packaged within a lipid envelope. The envelope contains spike-like projections, each being a homo-oligomer of one of three transmembrane viral envelope proteins: the attachment protein G, the fusion protein F involved in viral penetration and the small hydrofobic protein SH. The aim of this work was to construct two recombinant replication-defective adenoviruses carrying separately F and G genes from HRSV. This system was chosen because adenovirus delivers genes into target cells with high efficiency in a variety of cell lines and can be used in vitro and in vivo. In order to obtain the recombinant viruses, we did RT-PCR of RNA extracted from the HRSV A2 strain, the genes F and G were cloned in to pAdeno-X vectors. pAdeno-F and pAdeno-G were transfected in HEK-293 cells for the production of recombinant viruses, that expressed efficiently these two proteins and provide us the means for doing functional assays and immunization tests.O Vírus Sincicial Respiratório Humano (HRSV foi isolado e caracterizado pela primeira vez em 1957 e é considerado como o patógeno viral mais freqüente do trato respiratório de bebês e crianças. Apesar de muitos anos de pesquisa, não há ainda um tratamento específico ou uma vacina licenciada. Seu genoma é composto por uma fita simples de RNA polaridade negativa e o vírion consiste em um nucleocapsídeo empacotado por um envelope lipídico. O envelope contém projeções, chamadas espículas, constituídas de homoligômeros de uma das 3 glicoproteínas de membrana: a proteína de ligação G

  20. Comparative analysis of radiation- and virus-induced leukemias in BALB/c mice

    International Nuclear Information System (INIS)

    Newcomb, E.W.; Binari, R.; Fleissner, E.

    1985-01-01

    Endogenous murine leukemia virus (MuLV) proviral copies were analyzed in thymomas induced in normal BALB/c (Fv-1b) and in Fv-1n congenic mice by X-irradiation. Both strains of mice developed leukemia with similar kinetics, indicating that N-tropism of endogenous MuLV was not a rate-limiting factor in development of disease. Southern blot analysis, using a probe specific for ecotropic virus and for ecotropic-specific sequences retained in pathogenic, env-recombinant viruses, showed that the majority of radiation leukemias lacked newly acquired, clonally integrated, proviruses. This was in contrast to virus-induced leukemias, which routinely exhibited several new proviral integration sites. When an internal proviral DNA restriction fragment was monitored, some radiation leukemias showed evidence of nonclonal infection, accounting for more frequent isolation of infectious virus from such leukemias. Differences in expression of T-cell surface antigens were found in X-ray-induced and virus-induced leukemias. All radiation leukemias were TL positive, whereas virus-induced leukemias were primarily negative for TL. Some differences were also found in Lyt-1 and Lyt-2 expression. The data as a whole suggest that, in the majority of cases, radiation leukemogenesis is not initiated by a viral route--that is, the sort of viral mechanism for which exogenous infection by known pathogenic MuLV is the paradigm

  1. Comparative analysis of radiation- and virus-induced leukemias in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Newcomb, E.W.; Binari, R.; Fleissner, E.

    1985-01-15

    Endogenous murine leukemia virus (MuLV) proviral copies were analyzed in thymomas induced in normal BALB/c (Fv-1b) and in Fv-1n congenic mice by X-irradiation. Both strains of mice developed leukemia with similar kinetics, indicating that N-tropism of endogenous MuLV was not a rate-limiting factor in development of disease. Southern blot analysis, using a probe specific for ecotropic virus and for ecotropic-specific sequences retained in pathogenic, env-recombinant viruses, showed that the majority of radiation leukemias lacked newly acquired, clonally integrated, proviruses. This was in contrast to virus-induced leukemias, which routinely exhibited several new proviral integration sites. When an internal proviral DNA restriction fragment was monitored, some radiation leukemias showed evidence of nonclonal infection, accounting for more frequent isolation of infectious virus from such leukemias. Differences in expression of T-cell surface antigens were found in X-ray-induced and virus-induced leukemias. All radiation leukemias were TL positive, whereas virus-induced leukemias were primarily negative for TL. Some differences were also found in Lyt-1 and Lyt-2 expression. The data as a whole suggest that, in the majority of cases, radiation leukemogenesis is not initiated by a viral route--that is, the sort of viral mechanism for which exogenous infection by known pathogenic MuLV is the paradigm.

  2. Development of Treatment Strategies to Combat Ebola and Marburg Viruses

    Science.gov (United States)

    2006-02-02

    be needed. Several viruses require combination therapy to be effective; HIV and hepatits C virus . There is a paucity of compounds that are ready for...filovirus, Marburg virus , therapy, treatment Ebola and Marburg viruses are emerging/re-emerging pathogens that pose a significant threat to human...Previous library screening efforts were based on the use of surrogate viruses such as respiratory syncytial virus as a predictor of potential antivirals

  3. Interferon-γ-induced protein 10 in Dengue Virus infection.

    Science.gov (United States)

    Fallahi, P; Elia, G

    2016-01-01

    Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Interferons (IFNs), and IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ-induced protein 10 (IP-10), CXCL9/MIG and CXCL11/I-TAC, and their common receptor chemokine (C-X-C motif) receptor (CXCR)3 are induced by DENV infection; however it has been shown that the latter two could not compensate for the absence of IP-10. This paper reviews studies about DENV and IP-10. Evidences show the importance of IP-10 induction during DENV infection, in macrophages, lymphocytes, hepatic cells, denritic cells, in skin and in the brain. Furthermore it has been shown that chemokines IP-10, I-TAC and their receptor CXCR3 are involved in severity of dengue; in fact, pulmonary effusion or ascites, painful hepatomegaly or aspartate aminotransferase increase, are correlated with IP-10 levels. It has been also demonstrated that IP-10 was more elevated in subjects who subsequently developed dengue hemorrhagic fever or dengue shock syndrome. It has been also shown that IP-10 has a direct action in control of dengue viral replication. Furthermore IP-10 circulating levels may be used to discriminate dengue fever from other febbrile diseases. This is of particular importance in certain situations, for example to discriminate occupationally acquired dengue, in patients with febbrile disorders coming from endemic countries. These studies suggested that these chemokines can be used as potential biomarkers for differential diagnosis and the disease progression, while others can be used to control dengue viral replication, thus representing a viable targets for drug therapy.

  4. Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Cheng Jun

    2012-09-01

    Full Text Available Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC. Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV infection. Level of low density lipoprotein receptor (LDL-R and activity of peroxisome proliferator-activated receptor (PPAR α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP, and formation of very low density lipoprotein (VLDL have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN, HMG CoA reductase (HMGCR, liver X receptor (LXR, acetyl-CoA carboxylase 1 (ACC1, hepatic CB (1 receptors, retinoid X receptor (RXR α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

  5. Herpes Simplex Virus Type 1 Renders Infected Cells Resistant to Cytotoxic T-Lymphocyte-Induced Apoptosis

    OpenAIRE

    Jerome, Keith R.; Tait, Jonathan F.; Koelle, David M.; Corey, Lawrence

    1998-01-01

    Many viruses interfere with apoptosis of infected cells, presumably preventing cellular apoptosis as a direct response to viral infection. Since cytotoxic T lymphocytes (CTL) induce apoptosis of infected cells as part of the “lethal hit,” inhibition of apoptosis could represent an effective immune evasion strategy. We report here herpes simplex virus type 1 (HSV-1) interference with CTL-induced apoptosis of infected cells and show that HSV-1 inhibits the nuclear manifestations of apoptosis bu...

  6. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

  7. Tubular structure induced by a plant virus facilitates viral spread in its vector insect.

    Directory of Open Access Journals (Sweden)

    Qian Chen

    Full Text Available Rice dwarf virus (RDV replicates in and is transmitted by a leafhopper vector in a persistent-propagative manner. Previous cytopathologic and genetic data revealed that tubular structures, constructed by the nonstructural viral protein Pns10, contain viral particles and are directly involved in the intercellular spread of RDV among cultured leafhopper cells. Here, we demonstrated that RDV exploited these virus-containing tubules to move along actin-based microvilli of the epithelial cells and muscle fibers of visceral muscle tissues in the alimentary canal, facilitating the spread of virus in the body of its insect vector leafhoppers. In cultured leafhopper cells, the knockdown of Pns10 expression due to RNA interference (RNAi induced by synthesized dsRNA from Pns10 gene strongly inhibited tubule formation and prevented the spread of virus among insect vector cells. RNAi induced after ingestion of dsRNA from Pns10 gene strongly inhibited formation of tubules, preventing intercellular spread and transmission of the virus by the leafhopper. All these results, for the first time, show that a persistent-propagative virus exploits virus-containing tubules composed of a nonstructural viral protein to traffic along actin-based cellular protrusions, facilitating the intercellular spread of the virus in the vector insect. The RNAi strategy and the insect vector cell culture provide useful tools to investigate the molecular mechanisms enabling efficient transmission of persistent-propagative plant viruses by vector insects.

  8. Epstein–Barr virus particles induce centrosome amplification and chromosomal instability

    Science.gov (United States)

    Shumilov, Anatoliy; Tsai, Ming-Han; Schlosser, Yvonne T.; Kratz, Anne-Sophie; Bernhardt, Katharina; Fink, Susanne; Mizani, Tuba; Lin, Xiaochen; Jauch, Anna; Mautner, Josef; Kopp-Schneider, Annette; Feederle, Regina; Hoffmann, Ingrid; Delecluse, Henri-Jacques

    2017-01-01

    Infections with Epstein–Barr virus (EBV) are associated with cancer development, and EBV lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. Here we report that EBV infection of B-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. This effect can be reproduced with virus-like particles devoid of EBV DNA, but not with defective virus-like particles that cannot infect host cells. Viral protein BNRF1 induces centrosome amplification, and BNRF1-deficient viruses largely lose this property. These findings identify a new mechanism by which EBV particles can induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for development of tumours that do not necessarily carry the viral genome. PMID:28186092

  9. Epstein-Barr virus-induced systemic lupus erythematosus

    African Journals Online (AJOL)

    Ngou J. Graafland H, Segondy M. Antibodies against polypeptides of purified. Epstein-Barr virus in sera grown from patients with connective tissue diseases'. J Autoimmun 1992; 5: 243-249. 4. Stancek D, Rovensky J. Enhancement of Epstein-Barr virus antibody production in systemic lupus erythematosus patients.

  10. Identification of virus isolates inducing mosaic of sugarcane in ...

    African Journals Online (AJOL)

    SAM

    2014-03-19

    Mar 19, 2014 ... (JGMV), maize dwarf mosaic virus (MDMV) and sorghum mosaic Virus (SrMV) is an economically important viral disease of sugarcane ... race (“Bahausa”) and the least infected was the white land race (“fararkwama”). ... stripes symptoms on leaf blade and white stripe on stem in infected sugarcane and are ...

  11. Optimized cDNA libraries for virus-induced gene silencing (VIGS using tobacco rattle virus

    Directory of Open Access Journals (Sweden)

    Page Jonathan E

    2008-01-01

    Full Text Available Abstract Background Virus-induced gene silencing (VIGS has emerged as a method for performing rapid loss-of-function experiments in plants. Despite its expanding use, the effect of host gene insert length and other properties on silencing efficiency have not been systematically tested. In this study, we probed the optimal properties of cDNA fragments of the phytoene desaturase (PDS gene for efficient VIGS in Nicotiana benthamiana using tobacco rattle virus (TRV. Results NbPDS inserts of between 192 bp and 1304 bp led to efficient silencing as determined by analysis of leaf chlorophyll a levels. The region of the NbPDS cDNA used for silencing had a small effect on silencing efficiency with 5' and 3' located inserts performing more poorly than those from the middle. Silencing efficiency was reduced by the inclusion of a 24 bp poly(A or poly(G homopolymeric region. We developed a method for constructing cDNA libraries for use as a source of VIGS-ready constructs. Library construction involved the synthesis of cDNA on a solid phase support, digestion with RsaI to yield short cDNA fragments lacking poly(A tails and suppression subtractive hybridization to enrich for differentially expressed transcripts. We constructed two cDNA libraries from methyl-jasmonate treated N. benthamiana roots and obtained 2948 ESTs. Thirty percent of the cDNA inserts were 401–500 bp in length and 99.5% lacked poly(A tails. To test the efficiency of constructs derived from the VIGS-cDNA libraries, we silenced the nicotine biosynthetic enzyme, putrescine N-methyltransferase (PMT, with ten different VIGS-NbPMT constructs ranging from 122 bp to 517 bp. Leaf nicotine levels were reduced by more than 90% in all plants infected with the NbPMT constructs. Conclusion Based on the silencing of NbPDS and NbPMT, we suggest the following design guidelines for constructs in TRV vectors: (1 Insert lengths should be in the range of ~200 bp to ~1300 bp, (2 they should be positioned in

  12. ROLE OF MONOCYTES AND EOSINOPHILS IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION

    Science.gov (United States)

    Role of Monocytes and Eosinophils in Respiratory Syncytial Virus (RSV) InfectionJoleen M. Soukup and Susanne Becker US Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711;...

  13. [Observation of cells tolerant of tobacco mosaic virus in virus-induced local lesions in Datura stramonium L. leaves].

    Science.gov (United States)

    Reunov, A V; Lega, S N; Nagorskaia, V P; Lapshina, L A

    2011-01-01

    Ultrastructural examination of tobacco mosaic virus-induced local lesions developing in leaves of Datura stramonium plants demonstrated that, in the central area of the lesions, the cell response to viral invasion was not uniform. Most cells exhibited an acute hypersensitive reaction and underwent rapid and complete necrosis. However, some cells, despite considerable virus accumulation and immediate contact with completely collapsed cells, maintained a certain degree of structural integrity. Analysis performed showed that the proportion of collapsed and uncollapsed cells in the lesion centre 3 to 5 days after infection did not change essentially. These data suggest that the absence of hypersensitive response in some cells in the lesion centre is not due to an early stage of infection but is likely caused by cell tolerance of the virus.

  14. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

    1986-07-15

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.

  15. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    International Nuclear Information System (INIS)

    Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

    1986-01-01

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells

  16. Topoisomerase II Inhibitors Induce DNA Damage-Dependent Interferon Responses Circumventing Ebola Virus Immune Evasion.

    Science.gov (United States)

    Luthra, Priya; Aguirre, Sebastian; Yen, Benjamin C; Pietzsch, Colette A; Sanchez-Aparicio, Maria T; Tigabu, Bersabeh; Morlock, Lorraine K; García-Sastre, Adolfo; Leung, Daisy W; Williams, Noelle S; Fernandez-Sesma, Ana; Bukreyev, Alexander; Basler, Christopher F

    2017-04-04

    Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication. IMPORTANCE Ebola virus and other emerging RNA viruses are significant but unpredictable public health threats. Therapeutic approaches with broad-spectrum activity could provide an attractive response to such infections. We describe a novel assay that can identify small molecules that overcome Ebola virus-encoded innate immune evasion mechanisms. This assay identified as hits cancer chemotherapeutic drugs, including doxorubicin. Follow-up studies provide new insight into how doxorubicin induces interferon (IFN) responses, revealing activation of both the DNA damage response kinase ATM and the DNA sensor cGAS and its partner signaling protein STING. The studies further demonstrate that the ATM and cGAS-STING pathways o