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Sample records for adapted influenza virus

  1. Host adaptation and transmission of influenza A viruses in mammals

    E.J.A. Schrauwen (Eefje); R.A.M. Fouchier (Ron)

    2014-01-01

    textabstractA wide range of influenza A viruses of pigs and birds have infected humans in the last decade, sometimes with severe clinical consequences. Each of these so-called zoonotic infections provides an opportunity for virus adaptation to the new host. Fortunately, most of these human infection

  2. Fitness seascapes and adaptive evolution of the influenza virus

    Lassig, Michael

    2014-03-01

    The seasonal human influenza A virus undergoes rapid genome evolution. This process is triggered by interactions with the host immune system and produces significant year-to-year sequence turnover in the population of circulating viral strains. We develop a dynamical fitness model that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a viral strain: adaptive changes, which are under positive selection, and deleterious mutations, which affect conserved viral functions such as protein stability. Combined with the influenza strain tree, this fitness model maps the adaptive history of influenza A. We discuss the implications of our results for the statistical theory of adaptive evolution in asexual populations. Based on this and related systems, we touch upon the fundamental question of when evolution can be predicted. Joint work with Marta Luksza, Columbia University.

  3. Filamentous influenza viruses

    Dadonaite, Bernadeta; Vijyakrishnan, Swetha; Fodor, Ervin; Bhella, David; Hutchinson, Edward C.

    2016-01-01

    Clinical isolates of influenza virus produce pleomorphic virus particles, including extremely long filamentous virions. In contrast, strains of influenza that have adapted to laboratory growth typically produce only spherical virions. As a result, the filamentous phenotype has been overlooked in most influenza virus research. Recent advances in imaging and improved animal models have highlighted the distinct structure and functional relevance of filamentous virions. In this review we summaris...

  4. Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

    Jang, Yo Han; Byun, Young Ho; Lee, Yoon Jae; Lee, Yun Ha; Lee, Kwang-Hee; Seong, Baik Lin

    2012-01-01

    The rapid transmission of the pandemic 2009 H1N1 influenza virus (pH1N1) among humans has raised the concern of a potential emergence of reassortment between pH1N1 and highly pathogenic influenza strains, especially the avian H5N1 influenza virus. Here, we report that the cold-adapted pH1N1 live attenuated vaccine (CApH1N1) elicits cross-reactive immunity to seasonal and H5 influenza A viruses in the mouse model. Immunization with CApH1N1 induced both systemic and mucosal antibodies with broa...

  5. Impact of host cell line adaptation on quasispecies composition and glycosylation of influenza A virus hemagglutinin.

    Jana Verena Roedig

    Full Text Available The genome of influenza A viruses is constantly changing (genetic drift resulting in small, gradual changes in viral proteins. Alterations within antibody recognition sites of the viral membrane glycoproteins hemagglutinin (HA and neuraminidase (NA result in an antigenetic drift, which requires the seasonal update of human influenza virus vaccines. Generally, virus adaptation is necessary to obtain sufficiently high virus yields in cell culture-derived vaccine manufacturing. In this study detailed HA N-glycosylation pattern analysis was combined with in-depth pyrosequencing analysis of the virus genomic RNA. Forward and backward adaptation from Madin-Darby Canine Kidney (MDCK cells to African green monkey kidney (Vero cells was investigated for two closely related influenza A virus PR/8/34 (H1N1 strains: from the National Institute for Biological Standards and Control (NIBSC or the Robert Koch Institute (RKI. Furthermore, stability of HA N-glycosylation patterns over ten consecutive passages and different harvest time points is demonstrated. Adaptation to Vero cells finally allowed efficient influenza A virus replication in Vero cells. In contrast, during back-adaptation the virus replicated well from the very beginning. HA N-glycosylation patterns were cell line dependent and stabilized fast within one (NIBSC-derived virus or two (RKI-derived virus successive passages during adaptation processes. However, during adaptation new virus variants were detected. These variants carried "rescue" mutations on the genomic level within the HA stem region, which result in amino acid substitutions. These substitutions finally allowed sufficient virus replication in the new host system. According to adaptation pressure the composition of the virus populations varied. In Vero cells a selection for "rescue" variants was characteristic. After back-adaptation to MDCK cells some variants persisted at indifferent frequencies, others slowly diminished and even

  6. Environmental connections of novel avian-origin H7N9 influenza virus infection and virus adaptation to the human.

    Li, Jun; Yu, Xinfen; Pu, Xiaoying; Xie, Li; Sun, Yongxiang; Xiao, Haixia; Wang, Fenjuan; Din, Hua; Wu, Ying; Liu, Di; Zhao, Guoqiu; Liu, Jun; Pan, Jingcao

    2013-06-01

    A novel H7N9 influenza A virus has been discovered as the causative identity of the emerging acute respiratory infection cases in Shanghai, China. This virus has also been identified in cases of infection in the neighboring area Hangzhou City in Zhejiang Province. In this study, epidemiologic, clinical, and virological data from three patients in Hangzhou who were confirmed to be infected by the novel H7N9 influenza A virus were collected and analyzed. Human respiratory specimens and chicken feces from a contacted free market were tested for influenza virus by real-time reverse transcription PCR (RT-PCR) and sequencing. The clinical features of the three cases were similar featured with high fever and severe respiratory symptoms; however, only one of the patients died. A certain degree of diversity was observed among the three Hangzhou viruses sequenced from human samples compared with other reported H7N9 influenza A viruses. The sequences of the novel avian-origin H7N9 influenza viruses from Hangzhou City contained important amino acid substitutions related to human adaptation. One of the Hangzhou viruses had gained a novel amino acid substitution (Q226I) in the receptor binding region of hemagglutinin. More importantly, the virus sequenced from the chicken feces had a 627E substitution in the PB2 protein instead of the mammalian-adapted 627K substitution that was found in the PB2 proteins from the Hangzhou viruses from the three patients. Therefore, the newly-emerging H7N9 virus might be under adaptation pressure that will help it "jump" from avian to human hosts. The significance of these substitutions needs further exploration, with both laboratory experiments and extensive field surveillance. PMID:23657795

  7. THE BIOLOGY OF INFLUENZA VIRUSES

    Bouvier, Nicole M.; Palese, Peter

    2008-01-01

    The influenza viruses are characterized by segmented, negative-strand RNA genomes requiring an RNA-dependent RNA polymerase of viral origin for replication. The particular structure of the influenza virus genome and function of its viral proteins enable antigenic drift and antigenic shift. These processes result in viruses able to evade the long-term adaptive immune responses in many hosts.

  8. Equine H7N7 influenza A viruses are highly pathogenic in mice without adaptation: potential use as an animal model.

    Kawaoka, Y.

    1991-01-01

    Equine H7N7 influenza A viruses, representing a broad range of isolates, were lethal in mice without adaptation. After repeated passages, A/Equine/London/1416/73 acquired neurotropism upon intranasal infection. Thus, mice infected with equine influenza A viruses provide a model system for the study of highly virulent mammalian influenza viruses.

  9. Evolution and adaptation of the pandemic A/H1N1 2009 influenza virus

    Ducatez MF

    2011-07-01

    Full Text Available Mariette F Ducatez, Thomas P Fabrizio, Richard J WebbyDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USAAbstract: The emergence of the 2009 H1N1 pandemic influenza virus [A(H1N1pdm09] has provided the public health community with many challenges, but also the scientific community with an opportunity to monitor closely its evolution through the processes of drift and shift. To date, and despite having circulated in humans for nearly two years, little antigenic variation has been observed in the A(H1N1pdm09 viruses. However, as the A(H1N1pdm09 virus continues to circulate and the immunologic pressure within the human population increases, future antigenic change is almost a certainty. Several coinfections of A(H1N1pdm09 and seasonal A(H1N1 or A(H3N2 viruses have been observed, but no reassortant viruses have been described in humans, suggesting a lack of fitness of reassortant viruses or a lack of opportunities for interaction of different viral lineages. In contrast, multiple reassortment events have been detected in swine populations between A(H1N1 pdm09 and other endemic swine viruses. Somewhat surprisingly, many of the well characterized influenza virus virulence markers appear to have limited impact on the phenotype of the A(H1N1pdm09 viruses when they have been introduced into mutant viruses in laboratory settings. As such, it is unclear what the evolutionary path of the pandemic virus will be, but the monitoring of any changes in the circulating viruses will remain a global public and animal health priority.Keywords: influenza, pandemic, evolution, adaptation

  10. Generation and characterization of a cold-adapted attenuated live H3N2 subtype influenza virus vaccine candidate

    AN Wen-qi; LIU Xiu-fan; WANG Xi-liang; YANG Peng-hui; DUAN Yue-qiang; LUO De-yan; TANG Chong; JIA Wei-hong; XING Li; SHI Xin-fu; ZHANG Yu-jing

    2009-01-01

    Background H3N2 subtype influenza A viruses have been identified in humans worldwide, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. The aim of this study was to establish a system for rescuing of a cold-adapted high-yielding H3N2 subtype human influenza virus by reverse genetics. Methods In order to generate better and safer vaccine candidate viruses, a cold-adapted high yielding reassortant H3N2 influenza A virus was genetically constructed by reverse genetics and was designated as rgAA-H3N2. The rgAA-H3N2 virus contained HA and NA genes from an epidemic strain A/Wisconsin/67/2005 (H3N2) in a background of internal genes derived from the master donor viruses (MDV), cold-adapted (ca), temperature sensitive (te), live attenuated influenza virus strain A/Ann Arbor/6/60 (MDV-A). Results In this presentation, the virus HA titer of rgAA-H3N2 in the allantoic fluid from infected embryonated eggs was as high as 1:1024. A fluorescent focus assay (FFU) was performed 24-36 hours post-infection using a specific antibody and bright staining was used for determining the virus titer. The allantoic fluid containing the recovered influenza virus was analyzed in a hemagglutination inhibition (HI) test and the specific inhibition was found. Conclusion The results mentioned above demonstrated that cold-adapted, attenuated reassortant H3N2 subtype influenza A virus was successfully generated, which laid a good foundation for the further related research.

  11. Adaptation of high-growth influenza H5N1 vaccine virus in Vero cells: implications for pandemic preparedness.

    Tseng, Yu-Fen; Hu, Alan Yung-Chih; Huang, Mei-Liang; Yeh, Wei-Zhou; Weng, Tsai-Chuan; Chen, Yu-Shuan; Chong, Pele; Lee, Min-Shi

    2011-01-01

    Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14), a reassortant virus between A/Vietnam/1194/2004 (H5N1) virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15) was generated and can grow over 10(8) TCID(50)/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes. PMID:22022351

  12. Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans.

    Judith M Fonville

    Full Text Available Adaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus have been found in all sequenced human strains, while these substitutions have not been detected in any non-human A/H7N9 sequences. Given the currently available information, this observation suggests that the human-adaptive PB2 substitution might confer a fitness advantage to the virus in these human hosts that allows it to rise to proportions detectable by consensus sequencing over the course of a single human infection. We use a mathematical model of within-host virus evolution to estimate the fitness advantage required for a substitution to reach predominance in a single infection as a function of the duration of infection and the fraction of mutant present in the virus population that initially infects a human. The modeling results provide an estimate of the lower bound for the fitness advantage of this adaptive substitution in the currently sequenced A/H7N9 viruses. This framework can be more generally used to quantitatively estimate fitness advantages of adaptive substitutions based on the within-host prevalence of mutations. Such estimates are critical for models of cross-species transmission and host-adaptation of influenza virus infections.

  13. The Influenza Virus Enigma

    Salomon, Rachelle; Webster, Robert G.

    2009-01-01

    Both seasonal and pandemic influenza continue to challenge both scientists and clinicians. Drug-resistant H1N1 influenza viruses have dominated the 2009 flu season, and the H5N1 avian influenza virus continues to kill both people and poultry in Eurasia. Here, we discuss the pathogenesis and transmissibility of influenza viruses and we emphasize the need to find better predictors of both seasonal and potentially pandemic influenza.

  14. Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review.

    Munoz, Olga; De Nardi, Marco; van der Meulen, Karen; van Reeth, Kristien; Koopmans, Marion; Harris, Kate; von Dobschuetz, Sophie; Freidl, Gudrun; Meijer, Adam; Breed, Andrew; Hill, Andrew; Kosmider, Rowena; Banks, Jill; Stärk, Katharina D C; Wieland, Barbara; Stevens, Kim; van der Werf, Sylvie; Enouf, Vincent; Dauphin, Gwenaelle; Dundon, William; Cattoli, Giovanni; Capua, Ilaria

    2016-03-01

    In December 2011, the European Food Safety Authority awarded a Grant for the implementation of the FLURISK project. The main objective of FLURISK was the development of an epidemiological and virological evidence-based influenza risk assessment framework (IRAF) to assess influenza A virus strains circulating in the animal population according to their potential to cross the species barrier and cause infections in humans. With the purpose of gathering virological data to include in the IRAF, a literature review was conducted and key findings are presented here. Several adaptive traits have been identified in influenza viruses infecting domestic animals and a significance of these adaptations for the emergence of zoonotic influenza, such as shift in receptor preference and mutations in the replication proteins, has been hypothesized. Nonetheless, and despite several decades of research, a comprehensive understanding of the conditions that facilitate interspecies transmission is still lacking. This has been hampered by the intrinsic difficulties of the subject and the complexity of correlating environmental, viral and host factors. Finding the most suitable and feasible way of investigating these factors in laboratory settings represents another challenge. The majority of the studies identified through this review focus on only a subset of species, subtypes and genes, such as influenza in avian species and avian influenza viruses adapting to humans, especially in the context of highly pathogenic avian influenza H5N1. Further research applying a holistic approach and investigating the broader influenza genetic spectrum is urgently needed in the field of genetic adaptation of influenza A viruses. PMID:25630935

  15. Synergistic Effect of S224P and N383D Substitutions in the PA of H5N1 Avian Influenza Virus Contributes to Mammalian Adaptation

    Song, Jiasheng; Xu, Jing; Shi, Jianzhong; Li, Yanbing; Chen, Hualan

    2015-01-01

    The adaptation of H5N1 avian influenza viruses to human poses a great threat to public health. Previous studies indicate the adaptive mutations in viral polymerase of avian influenza viruses are major contributors in overcoming the host species barrier, with the majority of mammalian adaptive mutations occurring in the PB2 protein. However, the adaptive mutations in the PA protein of the H5N1 avian influenza virus are less defined and poorly understood. In this study, we identified the synergistic effect of the PA/224P + 383D of H5N1 avian influenza viruses and its ability to enhance the pathogenicity and viral replication in a mammalian mouse model. Interestingly, the signature of PA/224P + 383D mainly exists in mammalian isolates of the H5N1 influenza virus and pdmH1N1 influenza virus, providing a potential pathway for the natural adaptation to mammals which imply the effects of natural adaptation to mammals. Notably, the mutation of PA/383D, which is highly conserved in avian influenza viruses, increases the polymerase activity in both avian and human cells, and may have roles in maintaining the avian influenza virus in their avian reservoirs, and jumping species to infect humans. PMID:26000865

  16. Synergistic Effect of S224P and N383D Substitutions in the PA of H5N1 Avian Influenza Virus Contributes to Mammalian Adaptation

    Jiasheng Song; Jing Xu; Jianzhong Shi; Yanbing Li; Hualan Chen

    2015-01-01

    The adaptation of H5N1 avian influenza viruses to human poses a great threat to public health. Previous studies indicate the adaptive mutations in viral polymerase of avian influenza viruses are major contributors in overcoming the host species barrier, with the majority of mammalian adaptive mutations occurring in the PB2 protein. However, the adaptive mutations in the PA protein of the H5N1 avian influenza virus are less defined and poorly understood. In this study, we identified the synerg...

  17. Multifunctional adaptive NS1 mutations are selected upon human influenza virus evolution in the mouse.

    Nicole E Forbes

    Full Text Available The role of the NS1 protein in modulating influenza A virulence and host range was assessed by adapting A/Hong Kong/1/1968 (H3N2 (HK-wt to increased virulence in the mouse. Sequencing the NS genome segment of mouse-adapted variants revealed 11 mutations in the NS1 gene and 4 in the overlapping NEP gene. Using the HK-wt virus and reverse genetics to incorporate mutant NS gene segments, we demonstrated that all NS1 mutations were adaptive and enhanced virus replication (up to 100 fold in mouse cells and/or lungs. All but one NS1 mutant was associated with increased virulence measured by survival and weight loss in the mouse. Ten of twelve NS1 mutants significantly enhanced IFN-β antagonism to reduce the level of IFN β production relative to HK-wt in infected mouse lungs at 1 day post infection, where 9 mutants induced viral yields in the lung that were equivalent to or significantly greater than HK-wt (up to 16 fold increase. Eight of 12 NS1 mutants had reduced or lost the ability to bind the 30 kDa cleavage and polyadenylation specificity factor (CPSF30 thus demonstrating a lack of correlation with reduced IFN β production. Mutant NS1 genes resulted in increased viral mRNA transcription (10 of 12 mutants, and protein production (6 of 12 mutants in mouse cells. Increased transcription activity was demonstrated in the influenza mini-genome assay for 7 of 11 NS1 mutants. Although we have shown gain-of-function properties for all mutant NS genes, the contribution of the NEP mutations to phenotypic changes remains to be assessed. This study demonstrates that NS1 is a multifunctional virulence factor subject to adaptive evolution.

  18. Taming influenza viruses

    Ozawa, Makoto; Kawaoka, Yoshihiro

    2011-01-01

    Plasmid-based reverse genetics systems allow the artificial generation of viruses with cloned cDNA-derived genomes. Since the establishment of such systems for influenza virus, numerous attempts have been made to tame this pathogenic agent. In particular, several types of viruses expressing foreign genes have been generated and used to further our knowledge of influenza virus replication and pathogenicity and to develop novel influenza vaccines. Here, we review these achievements and discuss ...

  19. Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation.

    Arafa, A; Suarez, D; Kholosy, S G; Hassan, M K; Nasef, S; Selim, A; Dauphin, G; Kim, M; Yilma, J; Swayne, D; Aly, M M

    2012-10-01

    Highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first diagnosed in poultry in Egypt in 2006, and since then the disease became enzootic in poultry throughout the country, affecting the poultry industry and village poultry as well as infecting humans. Vaccination has been used as a part of the control strategy to help to control the disease. Epidemiological data with sequence analysis of H5N1 viruses is important to link the mechanism of virus evolution in Egypt. This study describes the evolutionary pattern of Egyptian H5N1 viruses based on molecular characterization for the isolates collected from commercial poultry farms and village poultry from 2006 to 2011. Genetic analysis of the hemagglutinin (HA) gene was done by sequencing of the full-length H5 gene. The epidemiological pattern of disease outbreaks in Egyptian poultry farms seems to be seasonal with no specific geographic distribution across the country. The molecular epidemiological data revealed that there are two major groups of viruses: the classic group of subclade 2.2.1 and a variant group of 2.2.1.1. The classic group is prevailing mainly in village poultry and had fewer mutations compared to the originally introduced virus in 2006. Since 2009, this group has started to be transmitted back to commercial sectors. The variant group emerged by late 2007, was prevalent mainly in vaccinated commercial poultry, mutated continuously at a higher rate until 2010, and started to decline in 2011. Genetic analysis of the neuraminidase (NA) gene and the other six internal genes indicates a grouping of the Egyptian viruses similar to that obtained using the HA gene, with no obvious reassortments. The results of this study indicate that HPAI-H5N1 viruses are progressively evolving and adapting in Egypt and continue to acquire new mutations every season. PMID:22760662

  20. Swine Influenza/Variant Influenza Viruses

    ... Documents (General) Workers Employed at Commercial Swine Farms Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... this? Submit Button Past Newsletters Information on Swine Influenza/Variant Influenza Viruses Language: English Español Recommend ...

  1. Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein.

    Benjamin Mänz

    2013-03-01

    Full Text Available The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP of pandemic strains A/Brevig Mission/1/1918 (1918 and A/Hamburg/4/2009 (pH1N1 that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1/04 (H5N1 resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.

  2. INFLUENZA VIRUS IN POULTRY

    Avian influenza virus (AIV) is normally found in wild birds, particularly in ducks and shorebirds, where it does not cause any perceptible clinical disease. However, poultry, including chickens and turkeys, are not normal hosts for avian influenza, but if the virus is introduced it can result in mi...

  3. Genetic Strategy to Prevent Influenza Virus Infections in Animals

    Chen, Jianzhu; Chen, Steve C.-Y.; Stern, Patrick; Scott, Benjamin B; Lois, Carlos

    2008-01-01

    The natural reservoirs of influenza viruses are aquatic birds. After adaptation, avian viruses can acquire the ability to infect humans and cause severe disease. Because domestic poultry serves as a key link between the natural reservoir of influenza viruses and epidemics and pandemics in human populations, an effective measure to control influenza would be to eliminate or reduce influenza virus infection in domestic poultry. The development and distribution of influenza-resistant poultry rep...

  4. Endocytosis of influenza viruses

    Lakadamyali, Melike; Rust, Michael J.; Zhuang, Xiaowei

    2004-01-01

    Receptor-mediated endocytosis is known to play an important role in the entry of many viruses into host cells. However, the exact internalization mechanism has, until recently, remained poorly understood for many medically important viruses, including influenza. Developments in real-time imaging of single viruses as well as the use of dominant negative mutants to selectively block specific endocytic pathways, have improved our understanding of the influenza infection process.

  5. Changes of morphological, biological and antigenic properties of avian influenza a virus hemagglutinin H2 in the course of adaptation to new host

    The alterations of avian influenza A virus hemagglutinin (HA) H2 as a result of adaptation to mice were first investigated in this study. HA of mouse-adapted (MA) variant was somewhat different from that of the original strain in electrophoretic mobility, antigenic structure and in hemagglutination activity with mouse red blood cells. (author)

  6. Amino acid substitutions occurring during adaptation of an emergent H5N6 avian influenza virus to mammals.

    Peng, Xiuming; Wu, Haibo; Peng, Xiaorong; Wu, Xiaoxin; Cheng, Linfang; Liu, Fumin; Ji, Shujing; Wu, Nanping

    2016-06-01

    Avian influenza viruses (AIVs) are known to cross species barriers, and emergent highly pathogenic H5N6 AIVs pose a serious threat to human health and the poultry industry. Here, we serially passaged an H5N6 virus 10 times in BALB/c mice. The pathogenicity of the wild-type 6D2 (WT-6D2) and mammal-adapted 6D2 strain (MA-6D2) were compared. The viral titer in multiple organs and the death rate for MA-6D2 were significantly higher than for WT-6D2. We provide evidence that the mutations HA A150V, NA R143K and G147E, PB2 E627K, and PA A343T may be important for adaptation of H5N6 AIVs to mammals. PMID:26997612

  7. Adaptation of High-Growth Influenza H5N1 Vaccine Virus in Vero Cells: Implications for Pandemic Preparedness

    Tseng, Yu-Fen; Hu, Alan Yung-Chih; Huang, Mei-Liang; Yeh, Wei-Zhou; Weng, Tsai-Chuan; Chen, Yu-Shuan; Chong, Pele; Lee, Min-Shi

    2011-01-01

    Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14), a reassortant virus between A/Vietnam/1194/2004 (H5N1) virus and egg-adap...

  8. Avian Influenza A Virus Infections in Humans

    ... Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Español Recommend on Facebook Tweet ... A Viruses Avian Influenza A Virus Infections in Humans Although avian influenza A viruses usually do not ...

  9. Replication and transmission of influenza viruses in Japanese quail

    Quail have emerged as a potential intermediate host in the spread of avian influenza A viruses in poultry in Hong Kong. To better understand this possible role, we tested the replication and transmission in quail of influenza A viruses of all 15 HA subtypes. Quail supported the replication of at least 14 subtypes. Influenza A viruses replicated predominantly in the respiratory tract. Transmission experiments suggested that perpetuation of avian influenza viruses in quail requires adaptation. Swine influenza viruses were isolated from the respiratory tract of quail at low levels. There was no evidence of human influenza A or B virus replication. Interestingly, a human-avian recombinant containing the surface glycoprotein genes of a quail virus and the internal genes of a human virus replicated and transmitted readily in quail; therefore, quail could function as amplifiers of influenza virus reassortants that have the potential to infect humans and/or other mammalian species

  10. Serological evaluation of an influenza A virus cold-adapted reassortant live vaccine, CR-37 (H1N1), in Japanese adult volunteers.

    Yamane, N; Nakamura, Y.; Yuki, M.; Odagiri, T.; Ishida, N

    1984-01-01

    A cold-adapted influenza A virus, CR-37 (H1N1), derived from genetic reassortment between A/Ann Arbor/6/60 (H2N2) cold-adapted variant virus and A/California/10/78 (H1N1) wild-type virus, was tested in Japanese adult volunteer. The CR-37 live virus preparation induced only low-grade clinical reactions in volunteers for the first 3-4 days after inoculation. Two vaccinees who did not show any antibody changes became febrile (over 38.0 degrees C). Skin tests using the vaccine preparation and uni...

  11. Avian influenza viruses in humans.

    Malik Peiris, J S

    2009-01-01

    Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to...

  12. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

  13. PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses

    Xiao, Chencheng; Ma, Wenjun; Sun, Na; Huang, Lihong; Li, Yaling; Zeng, Zhaoyong; Wen, Yijun; Zhang, Zaoyue; Li, Huanan; Li, Qian; Yu, Yuandi; Zheng, Yi; Liu, Shukai; Hu, Pingsheng; Zhang, Xu; Ning, Zhangyong; Qi, Wenbao; Liao, Ming

    2016-01-01

    Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588 V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells, and higher virulence in mice when compared to viruses with PB2-588 A. Analyses of available PB2 sequences showed that the proportion of avian H9N2 or human H7N9 influenza isolates bearing PB2-588 V has increased significantly since 2013. Taken together, our results suggest that the substitution PB2-A588V may be a new strategy for an avian influenza virus to adapt mammalian hosts. PMID:26782141

  14. Nucleocytoplasmic Shuttling of Influenza A Virus Proteins

    Jing Li

    2015-05-01

    Full Text Available Influenza viruses transcribe and replicate their genomes in the nuclei of infected host cells. The viral ribonucleoprotein (vRNP complex of influenza virus is the essential genetic unit of the virus. The viral proteins play important roles in multiple processes, including virus structural maintenance, mediating nucleocytoplasmic shuttling of the vRNP complex, virus particle assembly, and budding. Nucleocytoplasmic shuttling of viral proteins occurs throughout the entire virus life cycle. This review mainly focuses on matrix protein (M1, nucleoprotein (NP, nonstructural protein (NS1, and nuclear export protein (NEP, summarizing the mechanisms of their nucleocytoplasmic shuttling and the regulation of virus replication through their phosphorylation to further understand the regulation of nucleocytoplasmic shuttling in host adaptation of the viruses.

  15. The role of virus-specific human T cells in influenza A virus infection

    Guan, Jing; 管静

    2011-01-01

    Influenza A virus infection is a major cause of human morbidity and mortality. T cell immunity is believed to play critical roles for host defenses against influenza A infection. Once intracellular influenza A infection is established, viral clearance is mainly dependent on virus-specific CD8+ T cells. CD4+ T cells are important for adaptive immunity to natural influenza A infection or vaccination by providing help to B cells for antibody production and also providing help...

  16. Variant (Swine Origin) Influenza Viruses in Humans

    ... Past Newsletters Variant (Swine Origin) Influenza Viruses in Humans Language: English Español Recommend on Facebook Tweet ... Page Background Reporting Additional Information Key Facts about Human Infections with Variant Viruses (Swine Origin Influenza Viruses ...

  17. Intranasal Immunization with Influenza Virus-Like Particles Containing Membrane-Anchored Cholera Toxin B or Ricin Toxin B Enhances Adaptive Immune Responses and Protection against an Antigenically Distinct Virus

    Ji, Xianliang; Ren, Zhiguang; Xu, Na; Meng, Lingnan; Yu, Zhijun; Feng, Na; Sang, Xiaoyu; Li, Shengnan; Li, Yuanguo; Wang, Tiecheng; Zhao, Yongkun; Wang, Hualei; Zheng, Xuexing; Jin, Hongli; Li, Nan; Yang, Songtao; Cao, Jinshan; Liu, Wensen; Gao, Yuwei; Xia, Xianzhu

    2016-01-01

    Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs) composed of the hemagglutinin (HA), neuraminidase (NA) and matrix protein (M1) of A/Changchun/01/2009 (H1N1) with or without either membrane-anchored cholera toxin B (CTB) or ricin toxin B (RTB) as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival). Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses. PMID:27110810

  18. Novel hemagglutinin-based influenza virus inhibitors

    Shen, Xintian; Zhang, Xuanxuan; Liu, Shuwen

    2013-01-01

    Influenza virus has caused seasonal epidemics and worldwide pandemics, which caused tremendous loss of human lives and socioeconomics. Nowadays, only two classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase inhibitors respectively, are used for prophylaxis and treatment of influenza virus infection. Unfortunately, influenza virus strains resistant to one or all of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in influenza virus envelope, plays a c...

  19. Genetic Reassortment Among the Influenza Viruses (Avian Influenza, Human Influenza and Swine Influenza) in Pigs

    Dyah Ayu Hewajuli; Ni Luh Putu Indi Dharmiayanti

    2012-01-01

    Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries ...

  20. Avian influenza virus RNA extraction

    The efficient extraction and purification of viral RNA is critical for down-stream molecular applications whether it is the sensitive and specific detection of virus in clinical samples, virus gene cloning and expression, or quantification of avian influenza (AI) virus by molecular methods from expe...

  1. Evidence of expanded host range and mammalian-associated genetic changes in a duck H9N2 influenza virus following adaptation in quail and chickens.

    Md Jaber Hossain

    Full Text Available H9N2 avian influenza viruses continue to circulate worldwide; in Asia, H9N2 viruses have caused disease outbreaks and established lineages in land-based poultry. Some H9N2 strains are considered potentially pandemic because they have infected humans causing mild respiratory disease. In addition, some of these H9N2 strains replicate efficiently in mice without prior adaptation suggesting that H9N2 strains are expanding their host range. In order to understand the molecular basis of the interspecies transmission of H9N2 viruses, we adapted in the laboratory a wildtype duck H9N2 virus, influenza A/duck/Hong Kong/702/79 (WT702 virus, in quail and chickens through serial lung passages. We carried out comparative analysis of the replication and transmission in quail and chickens of WT702 and the viruses obtained after 23 serial passages in quail (QA23 followed by 10 serial passages in chickens (QA23CkA10. Although the WT702 virus can replicate and transmit in quail, it replicates poorly and does not transmit in chickens. In contrast, the QA23CkA10 virus was very efficient at replicating and transmitting in quail and chickens. Nucleotide sequence analysis of the QA23 and QA23CkA10 viruses compared to the WT702 virus indicated several nucleotide substitutions resulting in amino acid changes within the surface and internal proteins. In addition, a 21-amino acid deletion was found in the stalk of the NA protein of the QA23 virus and was maintained without further modification in the QA23CkA10 adapted virus. More importantly, both the QA23 and the QA23CkA10 viruses, unlike the WT702 virus, were able to readily infect mice, produce a large-plaque phenotype, showed faster replication kinetics in tissue culture, and resulted in the quick selection of the K627 amino acid mammalian-associated signature in PB2. These results are in agreement with the notion that adaptation of H9 viruses to land-based birds can lead to strains with expanded host range.

  2. PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses

    Chencheng Xiao; Wenjun Ma; Na Sun; Lihong Huang; Yaling Li; Zhaoyong Zeng; Yijun Wen; Zaoyue Zhang; Huanan Li; Qian Li; Yuandi Yu; Yi Zheng; Shukai Liu; Pingsheng Hu; Xu Zhang

    2016-01-01

    Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9...

  3. TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus

    Sakai, Kouji; Ami, Yasushi; Nakajima, Noriko; Nakajima, Katsuhiro; Kitazawa, Minori; Anraku, Masaki; Takayama, Ikuyo; Sangsriratanakul, Natthanan; Komura, Miyuki; Sato, Yuko; Asanuma, Hideki; Takashita, Emi; Komase, Katsuhiro; Takehara, Kazuaki; Tashiro, Masato; Hasegawa, Hideki; Odagiri, Takato; Takeda, Makoto

    2016-01-01

    Influenza A and B viruses show clear differences in their host specificity and pandemic potential. Recent studies have revealed that the host protease TMPRSS2 plays an essential role for proteolytic activation of H1, H3, and H7 subtype strains of influenza A virus (IAV) in vivo. IAV possessing a monobasic cleavage site in the haemagglutinin (HA) protein replicates poorly in TMPRSS2 knockout mice owing to insufficient HA cleavage. In the present study, human isolates of influenza B virus (IBV) strains and a mouse-adapted IBV strain were analysed. The data showed that IBV successfully underwent HA cleavage in TMPRSS2 knockout mice, and that the mouse-adapted strain was fully pathogenic to these mice. The present data demonstrate a clear difference between IAV and IBV in their molecular mechanisms for spreading in vivo. PMID:27389476

  4. TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus.

    Sakai, Kouji; Ami, Yasushi; Nakajima, Noriko; Nakajima, Katsuhiro; Kitazawa, Minori; Anraku, Masaki; Takayama, Ikuyo; Sangsriratanakul, Natthanan; Komura, Miyuki; Sato, Yuko; Asanuma, Hideki; Takashita, Emi; Komase, Katsuhiro; Takehara, Kazuaki; Tashiro, Masato; Hasegawa, Hideki; Odagiri, Takato; Takeda, Makoto

    2016-01-01

    Influenza A and B viruses show clear differences in their host specificity and pandemic potential. Recent studies have revealed that the host protease TMPRSS2 plays an essential role for proteolytic activation of H1, H3, and H7 subtype strains of influenza A virus (IAV) in vivo. IAV possessing a monobasic cleavage site in the haemagglutinin (HA) protein replicates poorly in TMPRSS2 knockout mice owing to insufficient HA cleavage. In the present study, human isolates of influenza B virus (IBV) strains and a mouse-adapted IBV strain were analysed. The data showed that IBV successfully underwent HA cleavage in TMPRSS2 knockout mice, and that the mouse-adapted strain was fully pathogenic to these mice. The present data demonstrate a clear difference between IAV and IBV in their molecular mechanisms for spreading in vivo. PMID:27389476

  5. Influenza Type A Viruses and Subtypes

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... this? Submit What's this? Submit Button Past Newsletters Influenza Type A Viruses Language: English Español Recommend ...

  6. The cold adapted and temperature sensitive influenza A/Ann Arbor/6/60 virus, the master donor virus for live attenuated influenza vaccines, has multiple defects in replication at the restrictive temperature

    We have previously determined that the temperature sensitive (ts) and attenuated (att) phenotypes of the cold adapted influenza A/Ann Arbor/6/60 strain (MDV-A), the master donor virus for the live attenuated influenza A vaccines (FluMist), are specified by the five amino acids in the PB1, PB2 and NP gene segments. To understand how these loci control the ts phenotype of MDV-A, replication of MDV-A at the non-permissive temperature (39 deg. C) was compared with recombinant wild-type A/Ann Arbor/6/60 (rWt). The mRNA and protein synthesis of MDV-A in the infected MDCK cells were not significantly reduced at 39 deg. C during a single-step replication, however, vRNA synthesis was reduced and the nuclear-cytoplasmic export of viral RNP (vRNP) was blocked. In addition, the virions released from MDV-A infected cells at 39 deg. C exhibited irregular morphology and had a greatly reduced amount of the M1 protein incorporated. The reduced M1 protein incorporation and vRNP export blockage correlated well with the virus ts phenotype because these defects could be partially alleviated by removing the three ts loci from the PB1 gene. The virions and vRNPs isolated from the MDV-A infected cells contained a higher level of heat shock protein 70 (Hsp70) than those of rWt, however, whether Hsp70 is involved in thermal inhibition of MDV-A replication remains to be determined. Our studies demonstrate that restrictive replication of MDV-A at the non-permissive temperature occurs in multiple steps of the virus replication cycle

  7. Low-pathogenic avian influenza viruses in wild house mice.

    Susan A Shriner

    Full Text Available BACKGROUND: Avian influenza viruses are known to productively infect a number of mammal species, several of which are commonly found on or near poultry and gamebird farms. While control of rodent species is often used to limit avian influenza virus transmission within and among outbreak sites, few studies have investigated the potential role of these species in outbreak dynamics. METHODOLOGY/PRINCIPAL FINDINGS: We trapped and sampled synanthropic mammals on a gamebird farm in Idaho, USA that had recently experienced a low pathogenic avian influenza outbreak. Six of six house mice (Mus musculus caught on the outbreak farm were presumptively positive for antibodies to type A influenza. Consequently, we experimentally infected groups of naïve wild-caught house mice with five different low pathogenic avian influenza viruses that included three viruses derived from wild birds and two viruses derived from chickens. Virus replication was efficient in house mice inoculated with viruses derived from wild birds and more moderate for chicken-derived viruses. Mean titers (EID(50 equivalents/mL across all lung samples from seven days of sampling (three mice/day ranged from 10(3.89 (H3N6 to 10(5.06 (H4N6 for the wild bird viruses and 10(2.08 (H6N2 to 10(2.85 (H4N8 for the chicken-derived viruses. Interestingly, multiple regression models indicated differential replication between sexes, with significantly (p<0.05 higher concentrations of avian influenza RNA found in females compared with males. CONCLUSIONS/SIGNIFICANCE: Avian influenza viruses replicated efficiently in wild-caught house mice without adaptation, indicating mice may be a risk pathway for movement of avian influenza viruses on poultry and gamebird farms. Differential virus replication between males and females warrants further investigation to determine the generality of this result in avian influenza disease dynamics.

  8. Avian influenza virus in pregnancy.

    Liu, Shelan; Sha, Jianping; Yu, Zhao; Hu, Yan; Chan, Ta-Chien; Wang, Xiaoxiao; Pan, Hao; Cheng, Wei; Mao, Shenghua; Zhang, Run Ju; Chen, Enfu

    2016-07-01

    The unprecedented epizootic of avian influenza viruses, such as H5N1, H5N6, H7N1 and H10N8, has continued to cause disease in humans in recent years. In 2013, another novel influenza A (H7N9) virus emerged in China, and 30% of those patients died. Pregnant women are particularly susceptible to avian influenza and are more likely to develop severe complications and to die, especially when infection occurs in the middle and late trimesters. Viremia is believed to occur infrequently, and thus vertical transmission induced by avian influenza appears to be rare. However, avian influenza increases the risk of adverse pregnancy outcomes, including spontaneous abortion, preterm birth and fatal distress. This review summarises 39 cases of pregnant women and their fetuses from different countries dating back to 1997, including 11, 15 and 13 infections with H7N9, H5N1 and the 2009 pandemic influenza (H1N1), respectively. We analysed the epidemic features, following the geographical, population and pregnancy trimester distributions; underlying diseases; exposure history; medical timelines; human-to-human transmission; pathogenicity and vertical transmission; antivirus treatments; maternal severity and mortality and pregnancy outcome. The common experiences reported in different countries and areas suggest that early identification and treatment are imperative. In the future, vigilant virologic and epidemiologic surveillance systems should be developed to monitor avian influenza viruses during pregnancy. Furthermore, extensive study on the immune mechanisms should be conducted, as this will guide safe, rational immunomodulatory treatment among this high-risk population. Most importantly, we should develop a universal avian influenza virus vaccine to prevent outbreaks of the different subtypes. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27187752

  9. Detection of influenza C virus but not influenza D virus in Scottish respiratory samples

    Smith, Donald B.; Gaunt, Eleanor R.; Digard, Paul; Templeton, Kate; Simmonds, Peter

    2016-01-01

    Highlights • “Influenza D” virus was not detected in Scottish respiratory samples (n = 3000). • Influenza C virus infection was present in 0.2% of respiratory samples. • Six influenza C virus complete genomes were sequenced. • Influenza C isolates comprised multiple, reassortant lineages.

  10. Molecular characterization of Indonesia avian influenza virus

    N.L.P.I. Dharmayanti

    2005-06-01

    Full Text Available Avian influenza outbreaks in poultry have been reported in Java island since August 2003. A total of 14 isolates of avian influenza virus has been isolated from October 2003 to October 2004. The viruses have been identified as HPAI H5N1 subtype. All of them were characterized further at genetic level and also for their pathogenicity. Phylogenetic analysis showed all of the avian influenza virus isolates were closely related to avian influenza virus from China (A/Duck/China/E319-2/03(H5N1. Molecular basis of pathogenicity in HA cleavage site indicated that the isolates of avian influenza virus have multiple basic amino acid (B-X-B-R indicating that all of the isolates representing virulent avian influenza virus (highly pathogenic avian influenza virus.

  11. H5N6 influenza virus infection, the newest influenza

    Beuy Joob

    2015-06-01

    Full Text Available The most recent new emerging infection is the H5N6 influenza virus infection. This infection has just been reported from China in early May 2014. The disease is believed to be a cross species infection. All indexed cases are from China. Of interest, the H5N6 influenza virus is the primary virus for avian. The avian H5N6 influenza virus in avian population is a low virulent strain. However, the clinical manifestation in human seems severe. In this mini-review, the authors summarize and discuss on this new emerging influenza.

  12. Identification of adaptive mutations in the influenza A virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.

    Nicole Forbes

    Full Text Available The NS1 protein of influenza A virus (IAV is a multifunctional virulence factor. We have previously characterized gain-of-function mutations in the NS1 protein arising from the experimental adaptation of the human isolate A/Hong Kong/1/1968(H3N2 (HK to the mouse. The majority of these mouse adapted NS1 mutations were demonstrated to increase virulence, viral fitness, and interferon antagonism, but differ in binding to the post-transcriptional processing factor cleavage and polyadenylation specificity factor 30 (CPSF30. Because nuclear trafficking is a major genetic determinant of influenza virus host adaptation, we assessed subcellular localization and host gene expression of NS1 adaptive mutations. Recombinant HK viruses with adaptive mutations in the NS1 gene were assessed for NS1 protein subcellular localization in mouse and human cells using confocal microscopy and cellular fractionation. In human cells the HK wild-type (HK-wt virus NS1 protein partitioned equivalently between the cytoplasm and nucleus but was defective in cytoplasmic localization in mouse cells. Several adaptive mutations increased the proportion of NS1 in the cytoplasm of mouse cells with the greatest effects for mutations M106I and D125G. The host gene expression profile of the adaptive mutants was determined by microarray analysis of infected mouse cells to show either high or low extents of host-gene regulation (HGR or LGR phenotypes. While host genes were predominantly down regulated for the HGR group of mutants (D2N, V23A, F103L, M106I+L98S, L98S, M106V, and M106V+M124I, the LGR phenotype mutants (D125G, M106I, V180A, V226I, and R227K were characterized by a predominant up regulation of host genes. CPSF30 binding affinity of NS1 mutants did not predict effects on host gene expression. To our knowledge this is the first report of roles of adaptive NS1 mutations that impact intracellular localization and regulation of host gene expression.

  13. Comparison of vaccines for induction of heterosubtypic immunity to influenza A virus: cold-adapted vaccine versus DNA prime-adenovirus boost strategies.

    Lo, Chia-Yun; Wu, Zhengqi; Misplon, Julia A; Price, Graeme E; Pappas, Claudia; Kong, Wing-Pui; Tumpey, Terrence M; Epstein, Suzanne L

    2008-04-16

    Influenza epidemics or pandemics can arise for which strain- or subtype-matched vaccines are unavailable. Heterosubtypic immunity (Het-I) targeting conserved influenza A antigens could reduce morbidity and mortality during preparation of matched vaccines. Various vaccines inducing Het-I in animals have been studied separately using different viruses and conditions, but effectiveness for inducing Het-I has not been directly compared. The present studies compared immunization with cold-adapted (ca) viruses to DNA prime-recombinant adenovirus (rAd) boost vaccination to conserved antigens nucleoprotein (NP), matrix-2 (M2), or A/NP+M2. Both ca and DNA-rAd vaccinations induced antibody and T cell responses, and protected against lethal H1N1 challenge. Only A/NP+M2 DNA-rAd protected against challenge with highly pathogenic A/Vietnam/1203/2004 (H5N1); ca vaccine did not. Existing ca vaccines may provide some Het-I, but experimental vaccination focusing on conserved antigens was more effective in this model for protection against a divergent, highly pathogenic virus. PMID:18378366

  14. Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs.

    Dwivedi, Varun; Manickam, Cordelia; Dhakal, Santosh; Binjawadagi, Basavaraj; Ouyang, Kang; Hiremath, Jagadish; Khatri, Mahesh; Hague, Jacquelyn Gervay; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-04-15

    Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract. PMID:27016770

  15. Avian influenza A viruses: From zoonosis to pandemic

    M. Richard (Mathilde); M.T. de Graaf (Marieke); S. Herfst (Sander)

    2014-01-01

    textabstractZoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in poul

  16. H5N6 influenza virus infection, the newest influenza

    Beuy Joob; Wiwanitkit Viroj

    2015-01-01

    The most recent new emerging infection is the H5N6 influenza virus infection. This infection has just been reported from China in early May 2014. The disease is believed to be a cross species infection. All indexed cases are from China. Of interest, the H5N6 influenza virus is the primary virus for avian. The avian H5N6 influenza virus in avian population is a low virulent strain. However, the clinical manifestation in human seems severe. In this mini-review, the authors summarize and discuss...

  17. The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice

    Wegmann, Frank; Moghaddam, Amin E.; Schiffner, Torben; Gartlan, Kate H.; Powell, Timothy J.; Russell, Rebecca A.; Baart, Matthijs; Carrow, Emily W.

    2015-01-01

    The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8+ T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines. PMID:26135973

  18. Role of receptor binding specificity in influenza A virus transmission and pathogenesis

    De Graaf, M.; Fouchier, R. A. M.

    2014-01-01

    The recent emergence of a novel avian A/H7N9 influenza virus in poultry and humans in China, as well as laboratory studies on adaptation and transmission of avian A/H5N1 influenza viruses, has shed new light on influenza virus adaptation to mammals. One of the biological traits required for animal influenza viruses to cross the species barrier that received considerable attention in animal model studies, in vitro assays, and structural analyses is receptor binding specificity. Sialylated glyc...

  19. Molecular characterization of Indonesia avian influenza virus

    N.L.P.I Dharmayanti; R Damayanti; R Indriani; A Wiyono; R.M.A Adjid

    2005-01-01

    Avian influenza outbreaks in poultry have been reported in Java island since August 2003. A total of 14 isolates of avian influenza virus has been isolated from October 2003 to October 2004. The viruses have been identified as HPAI H5N1 subtype. All of them were characterized further at genetic level and also for their pathogenicity. Phylogenetic analysis showed all of the avian influenza virus isolates were closely related to avian influenza virus from China (A/Duck/China/E319-2/03(H5N1). Mo...

  20. Evolution and ecology of influenza A viruses.

    Webster, R G; Bean, W J; Gorman, O T; Chambers, T M; Kawaoka, Y.

    1992-01-01

    In this review we examine the hypothesis that aquatic birds are the primordial source of all influenza viruses in other species and study the ecological features that permit the perpetuation of influenza viruses in aquatic avian species. Phylogenetic analysis of the nucleotide sequence of influenza A virus RNA segments coding for the spike proteins (HA, NA, and M2) and the internal proteins (PB2, PB1, PA, NP, M, and NS) from a wide range of hosts, geographical regions, and influenza A virus s...

  1. Molecular patterns of avian influenza A viruses

    KOU Zheng; LEI FuMin; WANG ShengYue; ZHOU YanHong; LI TianXian

    2008-01-01

    Avian influenza A viruses could get across the species barrier and be fatal to humans. Highly patho-genic avian influenza H5N1 virus was an example. The mechanism of interspecies transmission is not clear as yet. In this research, the protein sequences of 237 influenza A viruses with different subtypes were transformed into pseudo-signals. The energy features were extracted by the method of wavelet packet decomposition and used for virus classification by the method of hierarchical clustering. The clustering results showed that five patterns existed in avian influenza A viruses, which associated with the phenotype of interspecies transmission, and that avian viruses with patterns C and E could across species barrier and those with patterns A, B and D might not have the abilities. The results could be used to construct an early warning system to predict the transmissibility of avian influenza A viruses to humans.

  2. The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A h5N1 cold-adapted vaccine virus

    A recombinant live attenuated influenza virus (LAIV) deltaH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and the six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was attenuated in chickens, mice and fe...

  3. Identification of Newly Emerging Influenza Viruses by Surface-Enhanced Raman Spectroscopy.

    Lim, Jae-young; Nam, Jung-soo; Yang, Se-eun; Shin, Hyunku; Jang, Yoon-ha; Bae, Gyu-Un; Kang, Taewook; Lim, Kwang-il; Choi, Yeonho

    2015-12-01

    In this work, we demonstrate in situ virus identification based on surface-enhanced Raman scattering (SERS). We hypothesized that newly emerging influenza viruses possess surface proteins and lipids that can generate distinctive Raman signals. To test this hypothesis, SERS signals were measured from the surface of a noninfluenza virus, two different influenza viruses, and a genetically shuffled influenza virus. To ensure the safety for experimenters we constructed nonreplicating pseudotyped viruses that display main influenza virus surface components. Pseudotype with influenza virus components produced enhanced Raman peaks, on gold nanoparticles, that are easily distinguishable from those of pseudotype with a noninfluenza virus component, vesicular stomatitis virus G protein (VSVG). Furthermore, virus with the surface components of a newly emerging influenza strain, A/California/04/2009 (H1N1), generated Raman peaks different from those of viruses with components of the conventional laboratory-adapted influenza strain, A/WSN/33 (H1N1). Interestingly, the virus simultaneously displaying surface components of both influenza strains, a model mutant with genome reassortment, also produced a Raman signal pattern that is clearly distinguishable from those of each strain. This work highlights that SERS can provide a powerful label-free strategy to quickly identify newly emerging and potentially fatal influenza viruses. PMID:26528878

  4. Migratory birds and influenza virus

    Hubálek, Zdeněk

    Brno : ÚBO AV ČR, 2006 - (Procházka, P.; Sedláček, J.). s. 22-24 ISBN 80-903329-5-1. [Workshop of the Southeastern European Bird Migration Network (SEEN) /8./. 02.02.2006-05.02.2006, Praha] Institutional research plan: CEZ:AV0Z60930519 Keywords : migratory birds * influenza virus Subject RIV: EG - Zoology

  5. Characterization and evaluation of monoclonal antibodies developed for typing influenza A and influenza B viruses.

    Walls, H H; Harmon, M W; Slagle, J J; Stocksdale, C; Kendal, A P

    1986-01-01

    Monoclonal antibodies that are broadly reactive with influenza A or influenza B viruses were produced as stable reagents for typing influenza viruses. Monoclonal antibodies to influenza A were specific for either matrix protein or nucleoprotein. The antibodies to influenza B were specific for nucleoprotein or hemagglutinin protein. In an enzyme immunoassay procedure, influenza A antibodies detected H1N1, H2N2, and H3N2 influenza A virus strains collected between 1934 and 1984. Each of the inf...

  6. Immunity to seasonal and pandemic influenza A viruses

    Valkenburg, Sophie A.; Rutigliano, John A.; Ellebedy, Ali H.; Doherty, Peter C.; THOMAS, PAUL G.; Kedzierska, Katherine

    2011-01-01

    The introduction of a new influenza strain into human circulation leads to rapid global spread. This review summarizes innate and adaptive immunity to influenza viruses, with an emphasis on T-cell responses that provide cross-protection between distinct subtypes and strains. We discuss antigenic variation within T-cell immunogenic peptides and our understanding of pre-existing immunity towards the pandemic A(H1N1) 2009 strain.

  7. Immunology of avian influenza virus: a review.

    Suarez, D L; Schultz-Cherry, S

    2000-01-01

    Avian influenza virus can cause serious disease in a wide variety of birds and mammals, but its natural host range is in wild ducks, gulls, and shorebirds. Infections in poultry can be inapparent or cause respiratory disease, decreases in production, or a rapidly fatal systemic disease known as highly pathogenic avian influenza (HPAI). For the protection of poultry, neutralizing antibody to the hemagglutinin and neuraminidase proteins provide the primary protection against disease. A variety of vaccines elicit neutralizing antibody, including killed whole virus vaccines and fowl-pox recombinant vaccines. Antigenic drift of influenza viruses appears to be less important in causing vaccine failures in poultry as compared to humans. The cytotoxic T lymphocyte response can reduce viral shedding in mildly pathogenic avian influenza viruses, but provides questionable protection against HPAI. Influenza viruses can directly affect the immune response of infected birds, and the role of the Mx gene, interferons, and other cytokines in protection from disease remains unknown. PMID:10717293

  8. Emerging influenza virus: A global threat

    M Khanna; P Kumar; K Choudhary; B Kumar; V K Vijayan

    2008-11-01

    Since 1918, influenza virus has been one of the major causes of morbidity and mortality, especially among young children. Though the commonly circulating strain of the virus is not virulent enough to cause mortality, the ability of the virus genome to mutate at a very high rate may lead to the emergence of a highly virulent strain that may become the cause of the next pandemic. Apart from the influenza virus strain circulating in humans (H1N1 and H3N2), the avian influenza H5N1 H7 and H9 virus strains have also been reported to have caused human infections, H5N1 H7 and H9 have shown their ability to cross the species barrier from birds to humans and further replicate in humans. This review addresses the biological and epidemiological aspects of influenza virus and efforts to have a control on the virus globally.

  9. Cellular Proteins in Influenza Virus Particles

    Shaw, Megan L.; Stone, Kathryn L.; Colangelo, Christopher M.; Gulcicek, Erol E.; Peter Palese

    2008-01-01

    Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensi...

  10. Improving the representativeness of influenza viruses shared within the WHO Global Influenza Surveillance and Response System

    Pereyaslov, Dmitriy; Zemtsova, Galina; Gruessner, Christine; Daniels, Rodney S.; McCauley, John W.; Brown, Caroline S

    2016-01-01

    Background Sharing influenza viruses within the WHO Global Influenza Surveillance and Response System is crucial for monitoring evolution of influenza viruses. Objectives Analysis of timeliness and geographic representativeness of viruses shared by National Influenza Centres (NICs) in the WHO European Region with the London WHO Collaborating Centre for Reference and Research on Influenza for the Northern Hemisphere's 2010–2011 and 2011–2012 influenza seasons. Materials and methods Data from N...

  11. Cellular proteins in influenza virus particles.

    Megan L Shaw

    2008-06-01

    Full Text Available Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.

  12. Biopolymer encapsulated live influenza virus as a universal CD8+ T cell vaccine against influenza virus

    Boesteanu, Alina C.; Babu, Nadarajan S.; Wheatley, Margaret; Papazoglou, Elisabeth S.; Katsikis, Peter D.

    2010-01-01

    Current influenza virus vaccines primarily elicit antibodies and can be rendered ineffective by antigenic drift and shift. Vaccines that elicit CD8+ T cell responses targeting less variable proteins may function as universal vaccines that have broad reactivity against different influenza virus strains. To generate such a universal vaccine, we encapsulated live influenza virus in a biopolymer and delivered it to mice subcutaneously. This vaccine was safe, induced potent CD8+ T cell immunity an...

  13. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells.

    Wörmann, Xenia; Lesch, Markus; Welke, Robert-William; Okonechnikov, Konstantin; Abdurishid, Mirshat; Sieben, Christian; Geissner, Andreas; Brinkmann, Volker; Kastner, Markus; Karner, Andreas; Zhu, Rong; Hinterdorfer, Peter; Anish, Chakkumkal; Seeberger, Peter H; Herrmann, Andreas; Meyer, Thomas F; Karlas, Alexander

    2016-05-01

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA1 D130E, HA2 I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. PMID:26914510

  14. Epidemic Status of Swine Influenza Virus in China

    Kong, Weili; Ye, Jiahui; Guan, Shangsong; Liu, Jinhua; Pu, Juan

    2013-01-01

    As one of the most significant swine diseases, in recent years, swine influenza (SI) has had an immense impact on public health and has raised extensive public concerns in China. Swine are predisposed to both avian and human influenza virus infections, between that and/or swine influenza viruses, genetic reassortment could occur. This analysis aims at introducing the history of swine influenza virus, the serological epidemiology of swine influenza virus infection, the clinical details of swin...

  15. A brief introduction to avian influenza virus

    Avian influenza virus (AIV) causes a disease of high economic importance for poultry production worldwide. The earliest recorded cases of probable high pathogenicity AIV in poultry were reported in Italy in the 1870’s and avian influenza been recognized in domestic poultry through the modern era of ...

  16. Characterization of an H10N8 influenza virus isolated from Dongting lake wetland

    Chen Jianjun

    2011-01-01

    Full Text Available Abstract Background Wild birds, especially those in wetlands and aquatic environments, are considered to be natural reservoirs of avian influenza viruses. It is accepted that water is an important component in the transmission cycle of avian influenza virus. Monitoring the water at aggregation and breeding sites of migratory waterfowl, mainly wetland, is very important for early detection of avian influenza virus. The epidemiology investigation of avian influenza virus was performed in Dongting lake wetland which is an international important wetland. Results An H10N8 influenza virus was isolated from Dongting Lake wetland in 2007. Phylogenetic analysis indicated that the virus was generated by multiple gene segment reassortment. The isolate was lowly pathogenic for chickens. However, it replicated efficiently in the mouse lung without prior adaptation, and the virulence to mice increased rapidly during adaptation in mouse lung. Sequence analysis of the genome of viruses from different passages showed that multiple amino acid changes were involved in the adaptation of the isolates to mice. Conclusions The water might be an important component in the transmission cycle of avian influenza virus, and other subtypes of avian influenza viruses (other than H5, H7 and H9 might evolve to pose a potential threat to mammals and even humans.

  17. Biochemical Impact of the Host Adaptation-associated PB2 E627K Mutation on the Temperature-dependent RNA Synthesis Kinetics of Influenza A Virus Polymerase Complex*

    Aggarwal, Shilpa; Dewhurst, Stephen; Takimoto, Toru; Kim, Baek

    2011-01-01

    Most avian influenza A viruses, which preferentially replicate at the high temperatures found in the digestive tract of birds, have a glutamic acid at residue 627 of the viral RNA polymerase PB2 subunit (Glu-627), whereas the human viruses, which optimally replicate at the low temperatures observed in the human respiratory tract, have a lysine (Lys-627). The mechanism of action for this mutation is still not understood, although interaction with host factors has been proposed to play a major ...

  18. Avian Influenza Virus: The Threat of A Pandemic

    Shih-Cheng Chang; Yi-Ying Cheng; Shin-Ru Shih

    2006-01-01

    The 1918 influenza A virus pandemic caused a death toll of 40~50 million. Currently,because of the widespread dissemination of the avian influenza virus (H5N1), there is a highrisk of another pandemic. Avian species are the natural hosts for numerous subtypes ofinfluenza A viruses; however, the highly pathogenic avian influenza virus (HPAI) is not onlyextremely lethal to domestic avian species but also can infect humans and cause death. Thisreview discusses why the avian influenza virus is co...

  19. H5N1 influenza viruses: outbreaks and biological properties

    Neumann, Gabriele; Chen, Hualan; Gao, George F.; Shu, Yuelong; Kawaoka, Yoshihiro

    2009-01-01

    All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1...

  20. Avian Influenza A H7N9 Virus Induces Severe Pneumonia in Mice without Prior Adaptation and Responds to a Combination of Zanamivir and COX-2 Inhibitor

    Li, Can; Li, Chuangen; Anna J X Zhang; To, Kelvin K. W.; Andrew C Y Lee; Zhu, Houshun; Wu, Hazel W. L.; Chan, Jasper F. W.; Chen, Honglin; Hung, Ivan F. N.; Li, Lanjuan; Yuen, Kwok-Yung

    2014-01-01

    Background Human infection caused by the avian influenza A H7N9 virus has a case-fatality rate of over 30%. Systematic study of the pathogenesis of avian H7N9 isolate and effective therapeutic strategies are needed. Methods BALB/c mice were inoculated intranasally with an H7N9 virus isolated from a chicken in a wet market epidemiologically linked to a fatal human case, (A/chicken/Zhejiang/DTID-ZJU01/2013 [CK1]), and with an H7N9 virus isolated from a human (A/Anhui/01/2013 [AH1]). The pulmona...

  1. Recent zoonoses caused by influenza A viruses.

    Alexander, D J; Brown, I H

    2000-04-01

    Influenza is a highly contagious, acute illness which has afflicted humans and animals since ancient times. Influenza viruses are part of the Orthomyxoviridae family and are grouped into types A, B and C according to antigenic characteristics of the core proteins. Influenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals and birds, occasionally producing devastating pandemics in humans, such as in 1918, when over twenty million deaths occurred world-wide. The two surface glycoproteins of the virus, haemagglutinin (HA) and neuraminidase (NA), are the most important antigens for inducing protective immunity in the host and therefore show the greatest variation. For influenza A viruses, fifteen antigenically distinct HA subtypes and nine NA subtypes are recognised at present; a virus possesses one HA and one NA subtype, apparently in any combination. Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. In the 20th Century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, has occurred on four occasions, as follows, in 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each resulting in a pandemic. Frequent epidemics have occurred between the pandemics as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Currently, epidemics occur throughout the world in the human population due to infection with influenza A viruses of subtypes H1N1 and H3N2 or with influenza B virus. The impact of these epidemics is most effectively measured by monitoring excess mortality due to pneumonia and influenza. Phylogenetic studies suggest that aquatic birds could be the source of all influenza A viruses in other species. Human pandemic strains are thought to have emerged through one of the following three mechanisms: genetic reassortment (occurring as a

  2. Avian Influenza A (H7N9) Virus

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Submit What's this? Submit Button Past Newsletters Avian Influenza A (H7N9) Virus Language: English Español Recommend ...

  3. Transmission of Avian Influenza A Viruses Between Animals and People

    ... Newsletters Transmission of Avian Influenza A Viruses Between Animals and People Language: English Español Recommend on ... Compartir Influenza A viruses have infected many different animals, including ducks, chickens, pigs, whales, horses, and seals. ...

  4. M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A.

    Lorena Itatí Ibañez

    Full Text Available The ectodomain of influenza A matrix protein 2 (M2e is a candidate for a universal influenza A vaccine. We used recombinant Hepatitis B core antigen to produce virus-like particles presenting M2e (M2e-VLPs. We produced the VLPs with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. Immunization of BALB/c mice with M2e-VLPs containing nucleic acids induced a stronger, Th1-biased antibody response compared to particles lacking nucleic acids. The former also induced a stronger M2e-specific CD4(+ T cell response, as determined by ELISPOT. Mice vaccinated with alum-adjuvanted M2e-VLPs containing the nucleic acid-binding domain were better protected against influenza A virus challenge than mice vaccinated with similar particles lacking this domain, as deduced from the loss in body weight following challenge with X47 (H3N2 or PR/8 virus. Challenge of mice that had been immunized with M2e-VLPs with or without nucleic acids displayed significantly lower mortality, morbidity and lung virus titers than control-immunized groups. We conclude that nucleic acids present in M2e-VLPs correlate with improved immune protection.

  5. Avian influenza A viruses: from zoonosis to pandemic

    Richard, Mathilde; de Graaf, Miranda; Herfst, Sander

    2014-01-01

    Zoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in poultry in numerous countries in Europe, Asia and Africa, and the recently emerged H7N9 viruses in China, due to their relatively high number of human fatalities and pandemic potential. To start a pandemic, zoonot...

  6. The pathogenesis of H3N8 canine influenza virus in chickens and turkeys

    Canine influenza virus (CIV) of the H3N8 subtype has emerged in dog populations throughout the U.S. where it has become endemic in kennels and animal shelters in some regions of the U.S. CIV is believed to be an equine influenza that was transmitted to and adapted to dogs. It has not previously bee...

  7. Guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.

    Yipeng Sun

    Full Text Available BACKGROUND: The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. CONCLUSIONS/SIGNIFICANCE: We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses.

  8. Is low pathogenic avian influenza virus virulent for wild waterbirds?

    Kuiken, T

    2013-01-01

    Although low pathogenic avian influenza virus (LPAIV) is traditionally considered to have adapted to its wild waterbird host to become avirulent, recent studies have suggested that LPAIV infection might after all have clinical effects. Therefore, I reviewed the literature on LPAIV infections in wild waterbirds. The virulence of LPAIV was assessed in 17 studies on experimental infections and nine studies on natural infections. Reported evidence for virulence were reductions in return rate, fee...

  9. Influenza

    Ferroni, Eliana; Jefferson, Tom

    2011-01-01

    Influenza viruses are constantly altering their antigenic structure, and every year the WHO recommends which strains of influenza should be included in vaccines. During the autumn–winter months, influenza circulates more frequently (influenza seasons), causing a greater proportion of influenza-like illness and sometimes serious seasonal epidemics.The incidence of symptoms depends on the underlying immunity of the population.

  10. Influenza

    Jefferson, Tom

    2009-01-01

    Influenza viruses are constantly altering their antigenic structure, and every year the WHO recommends which strains of influenza should be included in vaccines. During the autumn-winter months, influenza circulates more frequently (influenza seasons), causing a greater proportion of influenza-like illness, and sometimes serious seasonal epidemics.The incidence of infection depends on the underlying immunity of the population.

  11. Nasal commensal Staphylococcus epidermidis counteracts influenza virus

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T.; Rohde, Holger; Gallo, Richard L.; Huang, Chun-Ming

    2016-01-01

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection. PMID:27306590

  12. Composting for Avian Influenza Virus Elimination

    Elving, Josefine; Emmoth, Eva; Albihn, Ann; Vinnerås, Björn; Ottoson, Jakob

    2012-01-01

    Effective sanitization is important in viral epizootic outbreaks to avoid further spread of the pathogen. This study examined thermal inactivation as a sanitizing treatment for manure inoculated with highly pathogenic avian influenza virus H7N1 and bacteriophages MS2 and ϕ6. Rapid inactivation of highly pathogenic avian influenza virus H7N1 was achieved at both mesophilic (35°C) and thermophilic (45 and 55°C) temperatures. Similar inactivation rates were observed for bacteriophage ϕ6, while b...

  13. Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses

    Maines, Taronna R; Chen, Li-Mei; Van Hoeven, Neal; Tumpey, Terrence M; Blixt, Ola; Belser, Jessica A; Gustin, Kortney M; Pearce, Melissa B; Pappas, Claudia; Stevens, James; Cox, Nancy J; Paulson, James C; Raman, Rahul; Sasisekharan, Ram; Katz, Jacqueline M; Donis, Ruben O

    2011-01-01

    Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced...

  14. Avian influenza viruses - new causative a gents of human infections

    Hrnjaković-Cvjetković Ivana; Cvjetković Dejan; Jerant-Patić Vera; Milošević Vesna; Tadić-Radovanov Jelena; Kovačević Gordana

    2006-01-01

    Introduction. Influenza A viruses can infect humans, some mammals and especially birds. Subtypes of human influenza A viruses: ACH1N1), ACH2N2) and A(H3N2) have caused pandemics. Avian influenza viruses vary owing to their 15 hemagglutinins (H) and 9 neuraminidases (N). Human cases of avian influenza A In the Netherlands in 2003, there were 83 human cases of influenza A (H7N7). In 1997, 18 cases of H5N1 influenza A, of whom 6 died, were found among residents of Hong Kong. In 2004, 34 human ca...

  15. Radioimmunoassay of influenza A virus haemagglutinin. II

    Individual rabbits differed greatly in their antibody response to the ''strain-specific'' and ''cross-reactive'' antigenic determinants on the hemagglutinin (HA) subunit of influenza virus recombinant MRC11 (H3N2) and influenza virus Dunedin (H3N2), after immunization with whole virus or bromelain-released hemagglutinin (B-HA). Consequently, diverse cross-reactions between these viruses and A/Hong Kong/68 virus were found in the hemagglutination inhibition (HI) test as well as in homologous radioimmunoassay (125I-B-HA from MRC11: anti MRC11 serum, and 125I-B-HA from Dunedin: anti Dunedin serum) when sera from different animals were employed. Radioimmunoassay (RIA), over and above to the HI test, was also able to differentiate clearly the respective HAs with antisera reacting to the same HI titre with both corresponding influenza virus strains. Thus it appeared that antigenic differences could be identified with higher sensitivity by homologous RIA than by the HI test and that multiple antigenic determinants were reactive on the 125I-B-HA in the RIA procedure employed. MRC11 and A/HK/68 viruses were also compared by heterologous RIA (125I-B-HA from MRC11: anti A/HK/68 serum). It was found that preferentially antigenic determinants with a high degree of cross-reactivity could be studied in the heterologous system. (author)

  16. THE MOLECULAR BIOLOGY OF AVIAN INFLUENZA VIRUS IN SHORT

    Avian influenza virus (AIV) is an important pathogen of poultry as it can cause severe economic losses through disease, including respiratory signs and mortality, and effects on trade. Avian influenza virus is classified as type A influenza, which is a member of the orthomyxoviridae family. Charact...

  17. Symptoms of influenza virus infection in hospitalized patients

    van den Dool, C; Hak, E; Wallinga, J; van Loon, A M; Lammers, J W J; Bonten, M J M

    2008-01-01

    BACKGROUND: During influenza outbreaks, fever and cough are the most accurate symptoms in predicting influenza virus infection in the community. OBJECTIVE: To determine the usefulness of fever, cough, and other symptoms for diagnosing influenza virus infection in hospitalized patients. DESIGN: Prosp

  18. Interaction of nanodiamonds materials with influenza viruses

    The perspectives of the application of modern materials contained nanodiamonds (ND) are considered in this study. The interaction between detonation paniculate ND, soot and influenza A and B viruses, fragments of cDNA were analyzed at the normal conditions. It was shown that these sorbents can interact with the following viruses: reference epidemic strains of influenza A(H1N1), A(H1N1)v, A(H3N2) and B viruses circulated in the word in 2000-2010. The allantoises, concentrated viruses, cDNA can be absorbed by ND sorbents and getting removed from water solutions within 20 min. ND sorbents can be used for the preparation of antivirus filters for water solution and for future diagnostic systems in virology.

  19. Radioimmunoassay of influenza A virus haemagglutinin. I

    Haemagglutinin released from influenza A virus recombinant MRC11 [antigenically identical to the strain A/Port Chalmers/1/73 (H3N2)] by bromelain treatment and purified by rate zonal centrifugation (further on B-HA) was examined for possible contamination by neuraminidase. Specific enzymatic activities of the MRC11 virus and the B-HA respectively showed that B-HA contained less than 0.1% of enzymatically active neuraminidase originally present in the virus. Gel double diffusion tests, specificities of rabbit antisera induced by B-HA as well as radioimmunoprecipitation experiments demonstrated that B-HA was devoid of any antigenically active neuraminidase. Precipitation of 125I-labelled B-HA with antisera to influenza virus recombinants with N2 neuraminidase was evidently caused by antibodies to host antigenic determinant(s) present in these sera. As for purity and radioimmunoprecipitation properties, B-HA is quite suitable for radioimmunoassay experiments. (author)

  20. Protective effects of phillyrin against influenza A virus in vivo.

    Qu, Xin-Yan; Li, Qing-Jun; Zhang, Hui-Min; Zhang, Xiao-Juan; Shi, Peng-Hui; Zhang, Xiu-Juan; Yang, Jing; Zhou, Zhe; Wang, Sheng-Qi

    2016-07-01

    Influenza A virus infection represents a great threat to public health. However, owing to side effects and the emergence of resistant virus strains, the use of currently available anti-influenza drugs may be limited. In order to identify novel anti-influenza drugs, we investigated the antiviral effects of phillyrin against influenza A virus infection in vivo. The mean survival time, lung index, viral titers, influenza hemagglutinin (HA) protein and serum cytokines levels, and histopathological changes in lung tissue were examined. Administration of phillyrin at a dose of 20 mg/kg/day for 3 days significantly prolonged the mean survival time, reduced the lung index, decreased the virus titers and interleukin-6 levels, reduced the expression of HA, and attenuated lung tissue damage in mice infected with influenza A virus. Taken together, these data showed that phillyrin had potential protective effects against infection caused by influenza A virus. PMID:27323762

  1. Avian Influenza: Mixed Infections and Missing Viruses

    Wentworth, David E.; Dugan, Vivien G.; Xudong Lin; Seth Schobel; Magdalena Plancarte; Kelly, Terra R.; Lindsay, LeAnn L.; Boyce, Walter M.

    2013-01-01

    A high prevalence and diversity of avian influenza (AI) viruses were detected in a population of wild mallards sampled during summer 2011 in California, providing an opportunity to compare results obtained before and after virus culture. We tested cloacal swab samples prior to culture by matrix real-time PCR, and by amplifying and sequencing a 640bp portion of the hemagglutinin (HA) gene. Each sample was also inoculated into embryonated chicken eggs, and full genome sequences were determined ...

  2. Emergence of European Avian Influenza Virus-Like H1N1 Swine Influenza A Viruses in China▿

    Liu, Jinhua; Bi, Yuhai; Qin, Kun; Fu, Guanghua; Yang, Jun; Peng, Jinshan; Ma, Guangpeng; Liu, Qinfang; Pu, Juan; Tian, Fulin

    2009-01-01

    During swine influenza surveillance from 2007 to 2008, 10 H1N1 viruses were isolated and analyzed for their antigenic and phylogenetic properties. Our study revealed the emergence of avian-origin European H1N1 swine influenza virus in China, which highlights the necessity of swine influenza surveillance for potential pandemic preparedness.

  3. Spatiotemporal Analysis of the Genetic Diversity of Seal Influenza A(H10N7) Virus, Northwestern Europe

    Bodewes, Rogier; Zohari, Siamak; Krog, Jesper Schak;

    2016-01-01

    birds to seals, amino acid changes in HA may occur rapidly and are important for virus adaptation to its new mammalian host. Influenza A viruses are major pathogens for humans, domestic animals, and wildlife. In addition to the continuous circulation of influenza A viruses among various host species...... to various avian influenza A(H10N7) viruses. The collection of samples from infected seals during the course of the outbreak provided a unique opportunity to follow the adaptation of the avian virus to its new seal host. Sequence data for samples collected from 41 different seals from four different...... found in H10 viruses isolated from Eurasian birds. Also, sequence variation in the HA gene was greater at the beginning than at the end of the epidemic, when a number of the mutations observed earlier had been fixed. These results imply that when an avian influenza virus jumps the species barrier from...

  4. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Irina Margine; Florian Krammer

    2014-01-01

    Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation wa...

  5. Current Approaches for Diagnosis of Influenza Virus Infections in Humans

    Vemula, Sai Vikram; Zhao, Jiangqin; Liu, Jikun; Wang, Xue; Biswas, Santanu; Hewlett, Indira

    2016-01-01

    Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemi...

  6. Influenza virus types and subtypes among pediatric patients having influenza like illness in summer season

    Bishwanath Acharya; Bishnu Prasad Upadhyay; Shailaja Adhikari; Ajit Rayamajhi; Kanchan Thapa

    2016-01-01

    Background: Acute respiratory infections (ARIs) represent one of the major causes of childhood mortality and morbidity in Nepal. The Influenza virus is one of the common causes of viral ARIs and bacterial infection secondary to influenza contributes to majority of childhood death worldwide. However, the diagnosis of influenza virus infection is not routinely suggested in Nepal even for children clinically presenting with influenza like illness (ILI). Methods: With an aim to describe the statu...

  7. Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

    We studied influenza virus M1 protein by generating HeLa and MDCK cell lines that express M1 genetically fused to green fluorescent protein (GFP). GFP-M1 was incorporated into virions produced by influenza virus infected MDCK cells expressing the fusion protein indicating that the fusion protein is at least partially functional. Following infection of either HeLa or MDCK cells with influenza A virus (but not influenza B virus), GFP-M1 redistributes from its cytosolic/nuclear location and accumulates in nuclear dots. Immunofluorescence revealed that the nuclear dots represent nuclear dot 10 (ND10) structures. The colocalization of authentic M1, as well as NS1 and NS2 protein, with ND10 was confirmed by immunofluorescence following in situ isolation of ND10. These findings demonstrate a previously unappreciated involvement of influenza virus with ND10, a structure involved in cellular responses to immune cytokines as well as the replication of a rapidly increasing list of viruses

  8. The pathogenesis of H3N8 canine influenza virus in chickens, turkeys and ducks

    Canine influenza virus (CIV) of the H3N8 subtype has emerged in dog populations throughout the U.S. where is has become endemic in kennels and animal shelters in some regions. It has not previously been determined whether the canine adapted virus can be transmitted to domestic poultry, which are su...

  9. El virus influenza y la gripe aviar

    Libia Herrero-Uribe

    2008-03-01

    Full Text Available En este artículo se presenta una revisión del virus influenza,su biología,sus mecanismos de variación antigénica,las pandemias que ha producido y la prevención mediante las vacunas y medicamentos antivirales.Se analizan las razones por las cuales aparece el virus H5N1 que produce la fiebre aviar en humanos,la patogénesis de este virus y las estrategias para su prevención.Se informa sobre el plan de preparación para la pandemia en los niveles nacional e internacional.

  10. Highly Pathogenic Avian Influenza Virus Infection in Feral Raccoons, Japan

    Horimoto, Taisuke; Maeda, Ken; Murakami, Shin; Kiso, Maki; Iwatsuki-Horimoto, Kiyoko; SASHIKA, Mariko; Ito, Toshihiro; Suzuki, Kazuo; Yokoyama, Mayumi; Kawaoka, Yoshihiro

    2011-01-01

    Although raccoons (Procyon lotor) are susceptible to influenza viruses, highly pathogenic avian influenza virus (H5N1) infection in these animals has not been reported. We performed a serosurvey of apparently healthy feral raccoons in Japan and found specific antibodies to subtype H5N1 viruses. Feral raccoons may pose a risk to farms and public health.

  11. Global migration of influenza A viruses in swine

    The emergence of the 2009 A/H1N1 pandemic virus underscores the importance of understanding how influenza A viruses evolve in swine on a global scale. To reveal the frequency, patterns and drivers of the spread of swine influenza virus globally, we conducted the largest phylogenetic analysis of swin...

  12. Avian influenza viruses - new causative a gents of human infections

    Hrnjaković-Cvjetković Ivana

    2006-01-01

    Full Text Available Introduction. Influenza A viruses can infect humans, some mammals and especially birds. Subtypes of human influenza A viruses: ACH1N1, ACH2N2 and A(H3N2 have caused pandemics. Avian influenza viruses vary owing to their 15 hemagglutinins (H and 9 neuraminidases (N. Human cases of avian influenza A In the Netherlands in 2003, there were 83 human cases of influenza A (H7N7. In 1997, 18 cases of H5N1 influenza A, of whom 6 died, were found among residents of Hong Kong. In 2004, 34 human cases (23 deaths were reported in Viet Nam and Thailand. H5N1 virus-infected patients presented with fever and respiratory symptoms. Complications included respiratory distress syndrome, renal failure, liver dysfunction and hematologic disorders. Since 1999, 7 cases of human influenza H9N2 infection have been identified in China and Hong Kong. The importance of human infection with avian influenza viruses. H5N1 virus can directly infect humans. Genetic reassortment of human and avian influenza viruses may occur in humans co infected with current human A(HIN1 or A(H3N2 subtypes and avian influenza viruses. The result would be a new influenza virus with pandemic potential. All genes of H5Nl viruses isolated from humans are of avian origin. Prevention and control. The reassortant virus containing H and N from avian and the remaining proteins from human influenza viruses will probably be used as a vaccine strain. The most important control measures are rapid destruction of all infected or exposed birds and rigorous disinfection of farms. Individuals exposed to suspected animals should receive prophylactic treatment with antivirals and annual vaccination. .

  13. Pathogenicity of highly pathogenic avian influenza virus in mammals

    de Wit, Emmie; Kawaoka, Yoshihiro; de Jong, Menno; Fouchier, Ron

    2008-01-01

    textabstractIn recent years, there has been an increase in outbreaks of highly pathogenic avian influenza (HPAI) in poultry. Occasionally, these outbreaks have resulted in transmission of influenza viruses to humans and other mammals, with symptoms ranging from conjunctivitis to pneumonia and death. Here, the current knowledge of the determinants of pathogenicity of HPAI viruses in mammals is summarized. It is becoming apparent that common mechanisms exist across influenza A virus strains and...

  14. Improved and simplified recombineering approach for influenza virus reverse genetics

    Liu, Qinfang; Wang, Shuai; Ma, Guangpeng; Pu, Juan; Forbes, Nicole E.; Brown, Earl G.; Liu, Jin-Hua

    2009-01-01

    Typical reverse genetics systems for generating influenza viruses require the insertion of each genome segments by DNA ligation into vectors for genome synthesis and expression. Herein is described the construction and use of a novel pair of plasmid vectors for cloning all eight genome segments of influenza A virus by homologous recombination for influenza virus reverse genetics. Plasmids, pLLBA and pLLBG, were constructed to possess opposing RNA polymerase I and RNA polymerase II transcripti...

  15. Animal Models for Influenza Virus Pathogenesis and Transmission

    Lowen, Anice C.; Bouvier, Nicole M.

    2010-01-01

    Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus in...

  16. The Regulation of Autophagy by Influenza A Virus

    Rong Zhang

    2014-01-01

    Full Text Available Influenza A virus is a dreadful pathogen of animals and humans, causing widespread infection and severe morbidity and mortality. It is essential to characterize the influenza A virus-host interaction and develop efficient counter measures against the viral infection. Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules. Recently, it has been shown that autophagy is a critical mechanism underlying the interaction between influenza A virus and its host. Autophagy can be induced by the infection with influenza A virus, which is considered as a necessary process for the viral proliferation, including the accumulation of viral elements during the replication of influenza A virus. On the other hand, influenza A virus can inhibit the autophagic formation via interaction with the autophagy-related genes (Atg and signaling pathways. In addition, autophagy is involved in the influenza virus-regulated cell deaths, leading to significant changes in host apoptosis. Interestingly, the high pathogenic strains of influenza A virus, such as H5N1, stimulate autophagic cell death and appear to interplay with the autophagy in distinct ways as compared with low pathogenic strains. This review discusses the regulation of autophagy, an influenza A virus driven process.

  17. Virulence of Avian Influenza A Viruses for Squirrel Monkeys

    Murphy, Brian R.; Hinshaw, Virginia S.; Sly, D. Lewis; London, William T.; Hosier, Nanette T.; Wood, Frank T.; Webster, Robert G.; Chanock, Robert M.

    1982-01-01

    Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus, A/Udorn/307/72 (H3N2). In squirrel monkeys, the 10 avian influenza A viruses exhibited a spectrum of replication and virulence. The levels of virus replication and clinical response were closely correlated. Two viruses, A/Mallard/NY/6874/78 (H3N2) and A/Pintail/Alb/121/79 (H7N8), resembled the human virus in t...

  18. The global antigenic diversity of swine influenza A viruses

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky;

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled...... with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic...... potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds...

  19. Influenza virus vaccine for neglected hosts: horses and dogs

    2016-01-01

    This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health. PMID:27489801

  20. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza

  1. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R., E-mail: grw7@cornell.edu

    2014-07-25

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

  2. Molecular diagnostics of Avian influenza virus

    Petrović Tamaš; Lazić Sava; Kapetanov Miloš; Velhner Maja

    2006-01-01

    The success of supervizing an infectious disease depends on the ability for speedy detection and characterization of the cause and the forming of a corresponding system for examining the success of control implemented in order to prevent a recurrence of the disease. Since influenza viruses continue to circle, causing significant morbidity and mortality both among the human population and among animals all over the world, it is essential to secure the timely identification and monitoring of th...

  3. Aerosolized avian influenza virus by laboratory manipulations

    Li Zhiping; Li Jinsong; Zhang Yandong; Li Lin; Ma Limin; Li Dan; Gao Feng; Xia Zhiping

    2012-01-01

    Abstract Background Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. Results Normal laboratory procedures used ...

  4. Transmission dynamics of Avian Influenza A virus

    Lu, Lu

    2015-01-01

    Influenza A virus (AIV) has an extremely high rate of mutation. Frequent exchanges of gene segments between different AIV (reassortment) have been responsible for major pandemics in recent human history. The presence of a wild bird reservoir maintains the threat of incursion of AIV into domestic birds, humans and other animals. In this thesis, I addressed unanswered questions of how diverse AIV subtypes (classified according to antigenicity of the two surface proteins, haema...

  5. The capillary electrophoresis of the influenza viruses

    Horká, Marie; Kubesová, Anna; Kubíček, O.; Kubíčková, Z.; Rosenbergová, K.; Šlais, Karel

    Tallinn: Tallinn University of Technology, 2009 - (Borissova, M.; Vaher, M.). s. 93 ISBN 978-9985-59-930-3. [Nordic Separation Science Society (NoSSS) International Conference /5./. 26.08.2009-29.08.2009, Tallinn] R&D Projects: GA AV ČR IAAX00310701 Institutional research plan: CEZ:AV0Z40310501 Keywords : capillary isoelectric focusing * capillary electrophoresis * influenza swine and equine viruses Subject RIV: CB - Analytical Chemistry, Separation

  6. Aerosolized avian influenza virus by laboratory manipulations

    Li Zhiping

    2012-08-01

    Full Text Available Abstract Background Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. Results Normal laboratory procedures used to process the influenza virus were carried out independently and the amount of virus polluting the on-site atmosphere was measured. In particular, zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation, and experimental zoogenetic infection were performed. In addition, common accidents associated with each process were simulated, including breaking glass containers, syringe injection of influenza virus solution, and rupturing of centrifuge tubes. A micro-cluster sampling ambient air pollution collection device was used to collect air samples. The collected viruses were tested for activity by measuring their ability to induce hemagglutination with chicken red blood cells and to propagate in chicken embryos after direct inoculation, the latter being detected by reverse-transcription PCR and HA test. The results showed that the air samples from the normal centrifugal group and the negative-control group were negative, while all other groups were positive for H5N1. Conclusions Our findings suggest that there are numerous sources of aerosols in laboratory operations involving H5N1. Thus, laboratory personnel should be aware of the exposure risk that accompanies routine procedures involved in H5N1 processing and take proactive measures to prevent accidental infection and decrease the risk of virus aerosol leakage beyond the laboratory.

  7. Structure of NS1A effector domain from the influenza A/Udorn/72 virus

    The structure of the effector domain of the influenza protein NS1, a validated antiviral drug target, has been solved in two space groups. The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented

  8. Structure of NS1A effector domain from the influenza A/Udorn/72 virus

    Xia, Shuangluo; Monzingo, Arthur F.; Robertus, Jon D., E-mail: jrobertus@mail.utexas.edu [Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, University of Texas, 1 University Station A5300, Austin, TX 78712 (United States)

    2009-01-01

    The structure of the effector domain of the influenza protein NS1, a validated antiviral drug target, has been solved in two space groups. The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented.

  9. Influenza virus infection, ozone exposure, and fibrogenesis.

    Jakab, G J; Bassett, D J

    1990-05-01

    Oxidant exposure following chemically induced lung injury exacerbates the tendency to develop pulmonary fibrosis. Influenza virus pneumonitis causes severe acute lung damage that, upon resolution, is followed by a persistent alveolitis and parenchymal changes characterized by patchy interstitial pneumonia and collagen deposition in the affected areas. To determine whether oxidant exposure exacerbates the virus-induced alveolitis and residual lung damage, mice were infected by aerosol inhalation with influenza A virus and continuously exposed to 0.5 ppm ozone or ambient air. Noninfected control mice were exposed to either ambient air or ozone. On various days during the first month after infection, groups of mice were sacrificed and their lungs assessed for acute injury (lung lavage albumin, total and differential cell counts, wet/dry ratios, and morphometry). At 30, 60, 90, and 120 days after infection, groups of mice were sacrificed for total and differential lavage cell counts, lung hydroxyproline content, and morphometric analysis. Ozone exposure did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 4, 7, 10, and 15 days after virus infection but mitigated the virus-induced acute lung injury by approximately 50%. After Day 30 a shift in the character of the pulmonary lesions was observed in that continuous exposure to ozone potentiated the postinfluenzal alveolitis and structural changes in the lung parenchyma. Additional studies suggest that the mechanism for the enhanced postinfluenzal lung damage may be related to the oxidant impairing the repair process of the acute influenzal lung damage. These data demonstrate that ozone exposure mitigates acute virus-induced lung injury and potentiates residual lung damage. PMID:2339849

  10. Characterization of influenza virus among influenza like illness cases in Mumbai, India.

    Roy, Soumen; Dahake, Ritwik; Patil, Deepak; Tawde, Shweta; Mukherjee, Sandeepan; Athlekar, Shrikant; Chowdhary, Abhay; Deshmukh, Ranjana

    2014-01-01

    The present study was carried out to monitor influenza viruses by identifying the virus and studying the seasonal variation during 2007-2009 in Mumbai. A total of 193 clinical respiratory samples (nasal and throat swab) were collected from patients having influenza like illness in Mumbai region. One-step real-time reverse-transcriptase PCR (rRTPCR) was used to detect Influenza type A (H1 and H3) and Influenza type B virus. Isolation of the virus was carried out using in vitro system which was further confirmed and typed by hemagglutination assay and hemagglutination inhibition assay. Out of 193 samples 24 (12.4 3%) samples tested positive for influenza virus, of which 13 (6.73 %) were influenza type A virus and 10 (5.18 %) were influenza type B virus, while 1 sample (0.51 %) was positive for both. By culture methods, 3 (1.55 %) viral isolates were obtained. All the three isolates were found to be Influenza type B/Malaysia (Victoria lineage) by Hemagglutination Inhibition Assay. The data generated from the present study reveals that both Influenza type A and B are prevalent in Mumbai with considerable activity. The peak activity was observed during monsoon season. PMID:25674606

  11. New world bats harbor diverse influenza A viruses.

    Suxiang Tong

    Full Text Available Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.

  12. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance

    Burnham, Andrew J.; Baranovich, Tatiana; Govorkova, Elena A.

    2013-01-01

    Many aspects of the biology and epidemiology of influenza B viruses are far less studied than for influenza A viruses, and one of these aspects is effectiveness and resistance to the clinically available antiviral drugs, the neuraminidase (NA) inhibitors (NAIs). Acute respiratory infections are one of the leading causes of death in children and adults, and influenza is among the few respiratory infections that can be prevented and treated by vaccination and antiviral treatment. Recent data ha...

  13. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

    Jong Seok Lee; Hye Suk Hwang; Eun-Ju Ko; Yu-Na Lee; Young-Man Kwon; Min-Chul Kim; Sang-Moo Kang

    2014-01-01

    Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE) has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8) probably in part through interference with the formation of reactive oxygen species by influenza A...

  14. Characterization of two influenza A viruses from a pilot whale.

    Hinshaw, V S; Bean, W J; Geraci, J.; Fiorelli, P; Early, G.; Webster, R G

    1986-01-01

    Influenza A viruses of the H13N2 and H13N9 subtypes were isolated from the lung and hilar node of a pilot whale. Serological, molecular, and biological analyses indicate that the whale isolates are closely related to the H13 influenza viruses from gulls.

  15. Avian Influenza Viruses in Water Birds, Africa 1

    Gaidet, Nicolas; Dodman, Tim; Caron, Alexandre; Balança, Gilles; Desvaux, Stephanie; Goutard, Flavie; Cattoli, Giovanni; Lamarque, François; Hagemeijer, Ward; Monicat, François

    2007-01-01

    We report the first large-scale surveillance of avian influenza viruses in water birds conducted in Africa. This study shows evidence of avian influenza viruses in wild birds, both Eurasian and Afro-tropical species, in several major wetlands of Africa.

  16. radioprotective and interferonogenic characteristics of influenza virus vaccine

    Different methods of prophylactic treatment with influenza virus vaccina increase survival of irradiated mice and hamsters by 25-55% as compared to unprotected ones. Higher radioresistance occurs in the same time intervals as a rise of interferon in the blood after immunization with influenza virus vaccine. 7 refs.; 2 figs.; 2 tabs

  17. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

    Jong Seok Lee

    2014-01-01

    Full Text Available Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8 probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

  18. Virulence of Avian Influenza A Viruses for Squirrel Monkeys

    Murphy, Brian R.; Hinshaw, Virginia S.; Sly, D. Lewis; London, William T.; Hosier, Nanette T.; Wood, Frank T.; Webster, Robert G.; Chanock, Robert M.

    1982-01-01

    Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus, A/Udorn/307/72 (H3N2). In squirrel monkeys, the 10 avian influenza A viruses exhibited a spectrum of replication and virulence. The levels of virus replication and clinical response were closely correlated. Two viruses, A/Mallard/NY/6874/78 (H3N2) and A/Pintail/Alb/121/79 (H7N8), resembled the human virus in their level and duration of replication and in their virulence. At the other end of the spectrum, five avian viruses were restricted by 100- to 10,000-fold in replication in the upper and lower respiratory tract and were clearly attenuated compared with the human influenza virus. In hamsters, the 10 viruses exhibited a spectrum of replication in the nasal turbinates, ranging from viruses that replicated as efficiently as the human virus to those that were 8,000- fold restricted. Since several avian viruses were closely related serologically to human influenza viruses, studies were done to confirm the avian nature of these isolates. Each of the avian viruses plaqued efficiently at 42°C, a restrictive temperature for replication of human influenza A viruses. Avian strains that had replicated either very efficiently or very poorly in squirrel monkeys still grew to high titer in the intestinal tracts of ducks, a tropism characteristic of avian, but not mammalian, influenza viruses. These observations indicate that some avian influenza A viruses grow well and cause disease in a primate host, whereas other avian viruses are very restricted in this host. These findings also provide a basis for determining the gene or genes involved in the restriction of replication that is observed with the attenuated avian viruses. Application of such information may allow the preparation of reassortant viruses derived from a virulent human influenza virus and an attenuated avian virus for possible

  19. Novel reassortant swine influenza viruses are circulating in Danish pigs

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona;

    The Danish surveillance program for influenza A virus in pigs has revealed that two novel reassortant swine influenza viruses may now be circulating in the Danish swine population, since they each have been detected in at least two submissions from different herds in 2011 as well as in 2012. One of...... the reassortant viruses comprised a HA gene similar to H1 of H1N1 avian-like swine influenza virus (SIV) and a NA gene most closely related to N2 gene of human H3N2 influenza virus that circulated in humans in the mid 1990s. The internal genes of this reassortant virus with the subtype H1avN2hu all...... pandemic H1N1pdm09 influenza virus lineage. Swine influenza virus with a similar subtype to H1pdm09N2sw has previously been found in pigs in Italy and Germany. Detailed analyses of viral genes will further elucidate the relationship between these new swine influenza viruses found in the different countries...

  20. The challenges of avian influenza virus: mechanism, epidemiology and control

    George F. GAO; Pang-Chui SHAW

    2009-01-01

    @@ Early 2009, eight human infection cases of H5N1 highly pathogenic avian influenza (HPAI) virus, with 5 death cases, were reported in China. This again made the world alert on a possible pandemic worldwide, probably caused by avian-origin influenza virus. Again H5N1 is in the spotlight of the world, not only for the scientists but also for the ordinary people. How much do we know about this virus? Where will this virus go and where did it come? Can we avoid a possible pandemic of influenza? Will the human beings conquer this devastating agent? Obviously we can list more questions than we know the answers.

  1. Current Approaches for Diagnosis of Influenza Virus Infections in Humans

    Vemula, Sai Vikram; Zhao, Jiangqin; Liu, Jikun; Wang, Xue; Biswas, Santanu; Hewlett, Indira

    2016-01-01

    Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans. PMID:27077877

  2. Influenza B Virus: Some Features of Clinical Findings and Etiotropic Treatment

    O. V. Maltsev; I. S. Grishin; E. V. Peredelsky; N. I. Lvov; K. V. Zhdanov

    2013-01-01

    Since January 1997 till March 2009 492 patients with a confirmed diagnosis of influenza A virus and influenza B virus underwent work-up in Military Medical Academy. It is established that the clinical findings of influenza B virus are accurately different from the clinical findings of influenza A virus. Influenza B virus is characterized by more prolonged fever, lower incidence and duration of some respiratory syndromes and fewer sequelae. The influence of etiotropic drugs and early interfero...

  3. Influenza Virus Resistance to Antiviral Agents: A Plea for Rational Use

    Poland, Gregory A.; Jacobson, Robert M.; Ovsyannikova, Inna G.

    2009-01-01

    Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. At the current time, nearly all influenza A/H3N2 viruses and a percentage of influenza A/H1N1 viruses are adamantane resistant, which leaves only neuraminidase inhibitors available for treatment of infection with these viruses. In December 2008, the Centers for Disease Control and Prevention released new data demonstrating that a high percenta...

  4. Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

    Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    Background: Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are lacking. The ruddy turnstone (Arenaria interpres) is the shorebird species with the highest prevalence of influenza virus at Delaware Bay. Objectives: The primary objective of this study was to experimentally assess the patterns of influenza virus excretion, minimal infectious doses, and clinical outcome in ruddy turnstones. Methods: We experimentally challenged ruddy turnstones using a common LPAIV shorebird isolate, an LPAIV waterfowl isolate, or a highly pathogenic H5N1 avian influenza virus. Cloacal and oral swabs and sera were analyzed from each bird. Results: Most ruddy turnstones had pre-existing antibodies to avian influenza virus, and many were infected at the time of capture. The infectious doses for each challenge virus were similar (103·6–104·16 EID50), regardless of exposure history. All infected birds excreted similar amounts of virus and showed no clinical signs of disease or mortality. Influenza A-specific antibodies remained detectable for at least 2 months after inoculation. Conclusions: These results provide a reference for interpretation of surveillance data, modeling, and predicting the risks of avian influenza transmission and movement in these important hosts.

  5. Avian influenza virus risk assessment in falconry

    Lüschow Dörte; Lierz Peter; Jansen Andreas; Harder Timm; Hafez Hafez; Kohls Andrea; Schweiger Brunhilde; Lierz Michael

    2011-01-01

    Abstract Background There is a continuing threat of human infections with avian influenza viruses (AIV). In this regard falconers might be a potential risk group because they have close contact to their hunting birds (raptors such as falcons and hawks) as well as their avian prey such as gulls and ducks. Both (hunting birds and prey birds) seem to be highly susceptible to some AIV strains, especially H5N1. We therefore conducted a field study to investigate AIV infections in falconers, their ...

  6. The variable codons of H5N1 avian influenza A virus haemagglutinin genes

    Mark; J.GIBBS; Robert; W.MURPHY

    2008-01-01

    We investigated the selection pressures on the haemagglutinin genes of H5N1 avian influenza viruses using fixed effects likelihood models. We found evidence of positive selection in the sequences from isolates from 1997 to 2007, except viruses from 2000. The haemagglutinin sequences of viruses from southeast Asia, Hong Kong and mainland China were the most polymorphic and had similar nonsyn-onymous profiles. Some sites were positively selected in viruses from most regions and a few of these sites displayed different amino acid patterns. Selection appeared to produce different outcomes in vi-ruses from Europe, Africa and Russia and from different host types. One position was found to be positively selected for human isolates only. Although the functions of some positively selected posi-tions are unknown, our analysis provided evidence of different temporal, spatial and host adaptations for H5N1 avian influenza viruses.

  7. Avian influenza virus and free-ranging wild birds

    Dierauf, Leslie A.; Karesh, W.B.; Ip, Hon S.; Gilardi, K.V.; Fischer, John R.

    2006-01-01

    Recent media and news reports and other information implicate wild birds in the spread of highly pathogenic avian influenza in Asia and Eastern Europe. Although there is little information concerning highly pathogenic avian influenza viruses in wild birds, scientists have amassed a large amount of data on low-pathogenicity avian influenza viruses during decades of research with wild birds. This knowledge can provide sound guidance to veterinarians, public health professionals, the general public, government agencies, and other entities with concerns about avian influenza.

  8. Antigenic characterization of influenza viruses produced using synthetic DNA and novel backbones.

    Suphaphiphat, Pirada; Whittaker, Lynne; De Souza, Ivna; Daniels, Rodney S; Dormitzer, Philip R; McCauley, John W; Settembre, Ethan C

    2016-07-12

    The global system for manufacturing seasonal influenza vaccines has been developed to respond to the natural evolution of influenza viruses, but the problem of antigenic mismatch continues to be a challenge in certain years. In some years, mismatches arise naturally due to the antigenic drift of circulating viruses after vaccine strain selection has already been made. In other years, antigenic differences between the vaccine virus and circulating viruses are introduced as part of the current system, which relies on the use of egg-adapted isolates as a starting material for candidate vaccine viruses (CVVs). Improving the current process for making vaccine viruses can provide great value. We have previously established a synthetic approach for rapidly generating influenza viruses in a vaccine-approved Madin Darby canine kidney (MDCK) cell line using novel, high-growth backbones that increase virus rescue efficiency and antigen yield. This technology also has the potential to produce viruses that maintain antigenic similarity to the intended reference viruses, depending on the hemagglutinin (HA) and neuraminidase (NA) sequences used for gene synthesis. To demonstrate this utility, we generated a panel of synthetic viruses using HA and NA sequences from recent isolates and showed by hemagglutination inhibition (HI) tests that all synthetic viruses were antigenically-like their conventional egg- or cell-propagated reference strains and there was no impact of the novel backbones on antigenicity. This synthetic approach can be used for the efficient production of CVVs that may be more representative of circulating viruses and may be used for both egg- and cell-based vaccine manufacturing platforms. When combined with mammalian cell culture technology for antigen production, synthetic viruses generated using HA and NA sequences from a non-egg-adapted prototype can help to reduce the potential impact of antigenic differences between vaccine virus and circulating viruses on

  9. The global antigenic diversity of swine influenza A viruses

    Lewis, Nicola S.; Russell, Colin A.; Langat, Pinky; Tavis K Anderson; Berger, Kathryn; Bielejec, Filip; Burke, David F.; Dudas, Gytis; Fonville, Judith M; Fouchier, Ron AM; Kellam, Paul; Koel, Bjorn F; Lemey, Philippe; Nguyen, Tung; Nuansrichy, Bundit

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigeni...

  10. Rapid preparation of mutated influenza hemagglutinins for influenza virus pandemic prevention

    Nishioka, Ryosuke; Satomura, Atsushi; Yamada, Junki; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2016-01-01

    Influenza viruses have periodically caused pandemic due to frequent mutation of viral proteins. Influenza viruses have two major membrane glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin plays a crucial role in viral entry, while NA is involved in the process of a viral escape. In terms of developing antiviral drugs, HA is a more important target than NA in the prevention of pandemic, since HA is likely to change the host specificity of a virus by acquiring mutations, t...

  11. Molecular diagnostics of Avian influenza virus

    Petrović Tamaš

    2006-01-01

    Full Text Available The success of supervizing an infectious disease depends on the ability for speedy detection and characterization of the cause and the forming of a corresponding system for examining the success of control implemented in order to prevent a recurrence of the disease. Since influenza viruses continue to circle, causing significant morbidity and mortality both among the human population and among animals all over the world, it is essential to secure the timely identification and monitoring of the strains that are in circulation. The speedy detection and characterization of new highly-virulent varieties is one of the priorities of the World Health Organization monitoring network. The implementation of molecular methods has an increasingly significant role in diagnostics and the monitoring of the influenza virus. Among a large number of molecular methods, the one particularly in use is the reverse transcription-polimerase chain reaction (PT-PCR. Technological progress in the area of the conducting of molecular methods has enabled that we can prove, in one day, using the RT-PCR method even very small quantities of the infective agent in a sample. In an obtained PCR product, we can relatively easily establish the nucleotide sequence, a detailed analysis and molecular epidemiology of the circulating strains. The molecular diagnostics procedure (RT-PCR is based on the correct choice or designing of primers depending on the desired knowledge. In order to obtain a specific diagnosis of influenza A, B or C, primers are used which multiply internal genes, such as the nucleoprotein (NP or matrix gene (M, because these are genes that are highly conserved among the virus types. In the event that we are interested in the subtype of influenza A, after obtaining a positive reaction, primers for genes of surface antigens are selected, such as hemagglutinin. Following the correct detection of the H subtype, it is possible to establish the virus virulence through the

  12. The high susceptibility of turkeys to influenza viruses of different origins implies their importance as potential intermediate hosts.

    Pillai, S P S; Pantin-Jackwood, M; Yassine, H M; Saif, Y M; Lee, C W

    2010-03-01

    Several previous reports and our studies show that waterfowl-origin influenza viruses can be more easily transmitted to domestic turkeys than chickens. Similarly, studies indicate turkeys to be better hosts for low pathogenic avian influenza viruses isolated from commercial poultry operations and live bird markets in comparison to chickens. Low 50% infectious-dose titers of wild bird as well as poultry-adapted viruses for turkeys further suggest that turkeys can be easily infected following a low-dose exposure. Also, interspecies transmission of swine influenza viruses to turkeys occurs frequently. These findings suggest the role of turkeys as suitable intermediate hosts that can be easily infected with influenza viruses of different origins and that turkeys can act as source of infection for other land-based poultry or even mammals. PMID:20521688

  13. Relationship of influenza virus infection to associated infections in children who present with influenza-like symptoms

    Norowitz, Yitzchok M.; Kohlhoff, Stephan; Smith-Norowitz, Tamar A

    2016-01-01

    Background Influenza virus is a major health care burden and is associated with significant morbidity and mortality. Data on morbidity and complications (pneumonia, otitis media) related to influenza virus infection in primary care settings are limited with reports mainly obtained from hospital settings. We assessed the prevalence of complications from viral/bacterial infections in influenza- positive compared with influenza- negative children presenting with influenza-like illness (ILI) in a...

  14. Monitoring Avian Influenza A(H7N9) Virus through National Influenza-like Illness Surveillance, China

    Xu, Cuiling; Havers, Fiona; Wang, Lijie; Tao CHEN; Shi, Jinghong; Wang, Dayan; YANG Jing; Lei YANG; Widdowson, Marc-Alain; Shu, Yuelong

    2013-01-01

    In China during March 4–April 28, 2013, avian influenza A(H7N9) virus testing was performed on 20,739 specimens from patients with influenza-like illness in 10 provinces with confirmed human cases: 6 (0.03%) were positive, and increased numbers of unsubtypeable influenza-positive specimens were not seen. Careful monitoring and rapid characterization of influenza A(H7N9) and other influenza viruses remain critical.

  15. Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis.

    Le, Vuong Ba; Schneider, Jochen; Boergeling, Yvonne; Berri, Fatma; Ducatez, Mariette; GUERIN, Jean-Luc; Adrian, Iris; Errazuriz-Cerda, Elisabeth; frasquilho, sonia; Antunes, Laurent; Lina, Bruno; Bordet, Jean-Claude; Jandrot-Perrus, Martine; Ludwig, Stephan; Riteau, Beatrice

    2015-01-01

    RATIONALE: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown. OBJECTIVES: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza. METHODS: We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza v...

  16. Avian Influenza: Mixed Infections and Missing Viruses

    David E. Wentworth

    2013-08-01

    Full Text Available A high prevalence and diversity of avian influenza (AI viruses were detected in a population of wild mallards sampled during summer 2011 in California, providing an opportunity to compare results obtained before and after virus culture. We tested cloacal swab samples prior to culture by matrix real-time PCR, and by amplifying and sequencing a 640bp portion of the hemagglutinin (HA gene. Each sample was also inoculated into embryonated chicken eggs, and full genome sequences were determined for cultured viruses. While low matrix Ct values were a good predictor of virus isolation from eggs, samples with high or undetectable Ct values also yielded isolates. Furthermore, a single passage in eggs altered the occurrence and detection of viral strains, and mixed infections (different HA subtypes were detected less frequently after culture. There is no gold standard or perfect reference comparison for surveillance of unknown viruses, and true negatives are difficult to distinguish from false negatives. This study showed that sequencing samples prior to culture increases the detection of mixed infections and enhances the identification of viral strains and sequences that may have changed or even disappeared during culture.

  17. Cocirculation of avian H9N2 and contemporary "human" H3N2 influenza A viruses in pigs in southeastern China: Potential for genetic reassortment?

    Peiris, J. S. M.; Guan, Y.; Markwell, D; Ghose, P.; Webster, R G; Shortridge, K. F.

    2001-01-01

    Pigs are permissive to both human and avian influenza viruses and have been proposed to be an intermediate host for the genesis of pandemic influenza viruses through reassortment or adaptation of avian viruses. Prospective virological surveillance carried out between March 1998 and June 2000 in Hong Kong, Special Administrative Region, People's Republic of China, on pigs imported from southeastern China, provides the first evidence of interspecies transmission of avian H9N2 viruses to pigs an...

  18. Dogs are highly susceptible to H5N1 avian influenza virus

    Chen, Ying; Zhong, Gongxun; Wang, Guojun; Deng, Guohua; Li, Yanbing; Shi, Jianzhong; Zhang, Zhuo; Guan, Yuntao; Jiang, Yongping; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2010-01-01

    Replication of avian influenza viruses (AIVs) in dogs may facilitate their adaptation in humans; however, the data to date on H5N1 influenza virus infection in dogs are conflicting. To elucidate the susceptibility of dogs to this pathogen, we infected two groups of 6 beagles with 106 50% egg-infectious dose of H5N1 AIV A/bar-headed goose/Qinghai/3/05 (BHG/QH/3/05) intranasally (i.n.) and intratracheally (i.t.), respectively. The dogs showed disease symptoms, including anorexic, fever, conjunc...

  19. A Review of Evidence that Equine Influenza Viruses Are Zoonotic.

    Xie, Tai; Anderson, Benjamin D; Daramragchaa, Ulziimaa; Chuluunbaatar, Maitsetset; Gray, Gregory C

    2016-01-01

    Among scientists, there exist mixed opinions whether equine influenza viruses infect man. In this report, we summarize a 2016 systematic and comprehensive review of the English, Chinese, and Mongolian scientific literature regarding evidence for equine influenza virus infections in man. Searches of PubMed, Web of Knowledge, ProQuest, CNKI, Chongqing VIP Database, Wanfang Data and MongolMed yielded 2831 articles, of which 16 met the inclusion criteria for this review. Considering these 16 publications, there was considerable experimental and observational evidence that at least H3N8 equine influenza viruses have occasionally infected man. In this review we summarize the most salient scientific reports. PMID:27420100

  20. A competitive-inhibiton radioimmunoassay for influenza virus envelope antigens

    A double-antibody competitive-inhibition radioimmunoassay for influenza virus envelope antigens is described. A viral antigen preparation from influenza A virus recombinant MRC11 [antigenically identical to A/Port Chalmers/1/73 (H3N2)] consisting of haemagglutinin and neuraminidase was labelled with radioiodine. Rabbit antisera were allowed to react with the labelled antigen and the resultant antigen-antibody complexes were precipitated with the appropriate antiglobulin. The competitive-inhibition radioimmunoassay very sensitively elucidated differences even among closely related influenza virus strains. Attempts have been made to eliminate neuraminidase from radioimmunoprecipitation to obtain a competitive-inhibition radioimmunoassay system for haemagglutinin alone. (author)

  1. Quantification of Influenza Virus RNA in Aerosols in Patient Rooms

    Leung, Nancy H. L.; Zhou, Jie; Daniel K W Chu; Yu, Han; William G. Lindsley; Beezhold, Donald H.; Yen, Hui-Ling; Li, Yuguo; Seto, Wing-Hong; Peiris, Joseph S. M.; Cowling, Benjamin J

    2016-01-01

    Background The potential for human influenza viruses to spread through fine particle aerosols remains controversial. The objective of our study was to determine whether influenza viruses could be detected in fine particles in hospital rooms. Methods and Findings We sampled the air in 2-bed patient isolation rooms for four hours, placing cyclone samplers at heights of 1.5m and 1.0m. We collected ten air samples each in the presence of at least one patient with confirmed influenza A virus infec...

  2. Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection

    Stevens, Natalie E.; Hatjopolous, Antoinette; Fraser, Cara K.; Alsharifi, Mohammed; Diener, Kerrilyn R.; Hayball, John D.

    2016-01-01

    Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus. PMID:27380890

  3. Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection.

    Stevens, Natalie E; Hatjopolous, Antoinette; Fraser, Cara K; Alsharifi, Mohammed; Diener, Kerrilyn R; Hayball, John D

    2016-01-01

    Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus. PMID:27380890

  4. Animal Models for Influenza Virus Pathogenesis and Transmission

    Anice C. Lowen

    2010-07-01

    Full Text Available Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein.

  5. El virus influenza y la gripe aviar Influenza virus and avian flu

    Libia Herrero-Uribe

    2008-03-01

    Full Text Available En este artículo se presenta una revisión del virus influenza,su biología,sus mecanismos de variación antigénica,las pandemias que ha producido y la prevención mediante las vacunas y medicamentos antivirales.Se analizan las razones por las cuales aparece el virus H5N1 que produce la fiebre aviar en humanos,la patogénesis de este virus y las estrategias para su prevención.Se informa sobre el plan de preparación para la pandemia en los niveles nacional e internacional.This article presents a review of Influenza virus,its biology,its mechanism of antigenic variation and its prevention by vaccination and the use of antivirals.The pandemics produced by this virus through history are presented.The appearance of the avian flu virus H5N1 is analyzed and its pathogenesis and strategies of prevention are discussed.National and international information about pandemic preparedness is presented.

  6. Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin

    Shuwen Liu; Jie Yang; Xintian Shen; Minmin Li

    2013-01-01

    Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Her...

  7. Pathobiology of avian influenza virus infections in wild birds

    Individual avian Influenza (AI) viruses vary in their ability to produce infection, disease and death in different bird species. Based on the pathobiological features in chickens, AI viruses (AIV) are categorized as low pathogenicity (LPAI) or high pathogenicity (HPAI) viruses, and can be of any of...

  8. Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7.

    van Zeijl, J.H.; Bakkers, J.; Wilbrink, B.; Melchers, W.J.; Mullaart, R.A.; Galama, J.M.

    2005-01-01

    During 2 consecutive influenza seasons we investigated the presence of influenza virus, human herpesvirus (HHV) type 6, and HHV-7 in cerebrospinal fluid samples from 9 white children suffering from influenza-associated encephalopathy. We conclude that it is unlikely that neuroinvasion by influenza v

  9. Practical aspects of vaccination of poultry against avian influenza virus

    Although little has changed in vaccine technology for avian influenza virus (AIV) in the past 20 years, the approach to vaccination of poultry (chickens, turkeys and ducks) for avian influenza has evolved as highly pathogenic (HP) AIV has become endemic in several regions of the world. Vaccination f...

  10. Influenza A virus pathogenesis and vaccination in swine

    Swine influenza is an acute respiratory disease of pigs that is characterized by fever followed by lethargy, anorexia, and serous nasal discharge. The disease progresses rapidly and may be complicated when associated with other respiratory pathogens. Influenza A virus (IAV) is one of the most preval...

  11. The quest of influenza A viruses for new hosts.

    Liu, M; Guan, Y; Peiris, M; He, S; Webby, R J; Perez, D; Webster, R G

    2003-01-01

    There is increasing evidence that stable lineages of influenza viruses are being established in chickens. H9N2 viruses are established in chickens in Eurasia, and there are increasing reports of H3N2, H6N1, and H6N2 influenza viruses in chickens both in Asia and North America. Surveillance in a live poultry market in Nanchang, South Central China, reveals that influenza viruses were isolated form 1% of fecal samples taken from healthy poultry over the course of 16 months. The highest isolation rates were from chickens (1.3%) and ducks (1.2%), followed by quail (0.8%), then pigeon (0.5%). H3N6, H9N2, H2N9, and H4N6 viruses were isolated from multiple samples, while single isolates of H1N1, H3N2, and H3N3 viruses were made. Representatives of each virus subtype were experimentally inoculated into both quail and chickens. All the viruses replicated in the trachea of quail, but efficient replication in chickens was confined to 25% of the tested isolates. In quail, these viruses were shed primarily by the aerosol route, raising the possibility that quail may be the "route modulator" that changes the route of transmission of influenza viruses from fecal-oral to aerosol transmission. Thus, quail may play an important role in the natural history of influenza viruses. The pros and cons of the use of inactivated and recombinant fowl pox-influenza vaccines to control the spread of avian influenza are also evaluated. PMID:14575076

  12. Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine

    Solórzano, Alicia; Foni, Emanuela; Córdoba, Lorena; Baratelli, Massimiliano; Razzuoli, Elisabetta; Bilato, Dania; Martín del Burgo, María Ángeles; Perlin, David S.; Martínez, Jorge; Martínez-Orellana, Pamela; Fraile, Lorenzo; Chiapponi, Chiara; Amadori, Massimo; del Real, Gustavo; Montoya, María

    2015-01-01

    Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed t...

  13. Prevention and Treatment of Avian Influenza A Viruses in People

    ... this? Submit What's this? Submit Button Past Newsletters Prevention and Treatment of Avian Influenza A Viruses in ... Recommend on Facebook Tweet Share Compartir The Best Prevention is to Avoid Sources of Exposure Currently, the ...

  14. Isolation of influenza viruses in MDCK 33016PF cells and clearance of contaminating respiratory viruses.

    Roth, Bernhard; Mohr, Hannah; Enders, Martin; Garten, Wolfgang; Gregersen, Jens-Peter

    2012-01-11

    This paper summarizes results obtained by multiplex PCR screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in MDCK 33016PF cells. Using the ResPlexII v2.0 (Qiagen) multiplex PCR, 393 positive results were obtained in 468 clinical samples collected during an influenza season in Germany. The overall distribution of positive results was influenza A 42.0%, influenza B 38.7%, adenovirus 1.5%, bocavirus 0.5%, coronavirus 3.3%, enterovirus 5.6%, metapneumovirus 1.0%, parainfluenza virus 0.8%, rhinovirus 4.1%, and respiratory syncytial virus (RSV) 2.5%. Double infections of influenza virus together with another virus were found for adenovirus B and E, bocavirus, coronavirus, enterovirus and for rhinovirus. These other viruses were rapidly lost upon passages in MDCK 33016PF cells and under conditions as applied to influenza virus passaging. Clinical samples, in which no influenza virus but other viruses were found, were also subject to passages in MDCK 33016PF cells. Using lower inoculum dilutions than those normally applied for preparations containing influenza virus (total dilution of the original sample of ∼10(4)), the positive results for the different viruses turned negative already after 2 or 3 passages in MDCK 33016PF cells. These results demonstrate that, under practical conditions as applied to grow influenza viruses, contaminating viruses can be effectively removed by passages in MDCK cells. In combination with their superior isolation efficiency, MDCK cells appear highly suitable to be used as an alternative to embryonated eggs to isolate and propagate influenza vaccine candidate viruses. PMID:22119922

  15. Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies.

    Fukuyama, Satoshi; Katsura, Hiroaki; Zhao, Dongming; Ozawa, Makoto; Ando, Tomomi; Shoemaker, Jason E; Ishikawa, Izumi; Yamada, Shinya; Neumann, Gabriele; Watanabe, Shinji; Kitano, Hiroaki; Kawaoka, Yoshihiro

    2015-01-01

    Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours ('Color-flu' viruses) to facilitate the study of viral infection in in vivo models. On adaptation to mice, stable expression of the fluorescent proteins in infected animals allows their detection by different types of microscopy and by flow cytometry. We use this system to analyse the progression of viral spread in mouse lungs, for live imaging of virus-infected cells, and for differential gene expression studies in virus antigen-positive and virus antigen-negative live cells in the lungs of Color-flu-infected mice. Collectively, Color-flu viruses are powerful tools to analyse virus infections at the cellular level in vivo to better understand influenza pathogenesis. PMID:25807527

  16. The Irrationality of GOF Avian Influenza Virus Research

    Wain-Hobson, Simon

    2014-01-01

    The last two and a half years have witnessed a curious debate in virology characterized by a remarkable lack of discussion. It goes by the misleading epithet “gain of function” (GOF) influenza virus research, or simply GOF. As will be seen, there is nothing good to be gained. The controversial experiments confer aerosol transmission on avian influenza virus strains that can infect humans, but which are not naturally transmitted between humans. Some of the newer strains are clearly highly path...

  17. Ecology, Evolution and Pathogenesis of Avian Influenza Viruses

    Munster, Vincent

    2006-01-01

    textabstractInfluenza A virus behoort tot de familie van Orthomyxoviridae. Infl uenza A virussen zijn onregelmatig gevormde virussen van ongeveer 120 nm groot. Het genoom van influenza A virussen is gesegmenteerd en bestaat uit negatief-strengs RNA. De acht gensegmenten coderen voor 11 verschillende eiwitten. Infl uenza A virussen worden onderverdeeld op basis van de oppervlakte eiwitten; hemagglutinine (HA, een eiwit dat zorg draagt voor de binding van het virus aan en binnendringen van de g...

  18. Detecting emerging transmissibility of avian influenza virus in human households

    van Boven, M.; Koopmans, M.; Du Ry van Beest Holle, M.; Meijer, Adam; Klinkenberg, D.; Donnelly, C. A.; Heesterbeek, J A P

    2007-01-01

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i) the animal reservoir, (ii) humans who were infected b...

  19. Pandemic swine influenza virus (H1N1): A threatening evolution.

    Khanna, Madhu; Kumar, Binod; Gupta, Neha; Kumar, Prashant; Gupta, Ankit; Vijayan, V K; Kaur, Harpreet

    2009-12-01

    "Survival of the fittest" is an old axiom laid down by the great evolutionist Charles Darwin and microorganisms seem to have exploited this statement to a great extent. The ability of viruses to adapt themselves to the changing environment has made it possible to inhabit itself in this vast world for the past millions of years. Experts are well versed with the fact that influenza viruses have the capability to trade genetic components from one to the other within animal and human population. In mid April 2009, the Centers for Disease Control and Prevention and the World Health Organization had recognized a dramatic increase in number of influenza cases. These current 2009 infections were found to be caused by a new strain of influenza type A H1N1 virus which is a re-assortment of several strains of influenza viruses commonly infecting human, avian, and swine population. This evolution is quite dependent on swine population which acts as a main reservoir for the reassortment event in virus. With the current rate of progress and the efforts of heath authorities worldwide, we have still not lost the race against fighting this virus. This article gives an insight to the probable source of origin and the evolutionary progress it has gone through that makes it a potential threat in the future, the current scenario and the possible measures that may be explored to further strengthen the war against pandemic. PMID:23100799

  20. Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2.

    Li, Junwei; Ishaq, Musarat; Prudence, Mabiala; Xi, Xiao; Hu, Tao; Liu, Qingzhen; Guo, Deyin

    2009-09-01

    To understand the adaptation of H5N1 influenza viruses to mammals, a non-pathogenic influenza H5N1 virus (HN021) in mice was passaged for 15 times in mammalian host. Animal experimental results indicated that the mouse-adapted (MA) variants became highly pathogenic in mice after the passages. Sequence analysis showed that there was one amino acid substitution in PB2 protein of MA mutants after first passage (MA1), three amino acid substitutions in PB2 protein of MA5 and one amino acid in M1 protein, seven amino acids in HA protein and seven amino acids in PB2 protein of MA15, respectively. Animal experiments and growth assays with reassortant viruses produced by reverse genetics showed that mutations in PB2 alone contributed to the increase in virulence of HN021 in mice. Polymerase activity assays showed that the mutations in PB2 enhanced ribonucleoprotein complex polymerase activity in mammalian cells. Interestingly, one reverse mutation (K627E) took place at the amino acid position 627 of PB2 during passages of MA5 to MA15, indicating that a lysine at position 627 of PB2 is not absolutely needed for virulence and adaptation in mice by H5N1 virus. Taken together, the results suggest that mutations at multiple sites of PB2 contributed to the virulence and adaptation in mice, and the E627K mutation of PB2 is not an indispensable determinant in PB2 for mammalian adaptation by H5N1 avian influenza virus. PMID:19393699

  1. Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses

    Lin-Lin Ma; Miao Ge; Hui-Qiang Wang; Jin-Qiu Yin; Jian-Dong Jiang; Yu-Huan Li

    2015-01-01

    Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge. Here, 10 oral proprietary Chinese medicines were selected to evaluate their anti-influenza activities. These drugs exhibit potent inhibitory effects against influenza A H1N1, influenza A H3N2, and influenza B virus...

  2. Avian influenza virus risk assessment in falconry

    Lüschow Dörte

    2011-04-01

    Full Text Available Abstract Background There is a continuing threat of human infections with avian influenza viruses (AIV. In this regard falconers might be a potential risk group because they have close contact to their hunting birds (raptors such as falcons and hawks as well as their avian prey such as gulls and ducks. Both (hunting birds and prey birds seem to be highly susceptible to some AIV strains, especially H5N1. We therefore conducted a field study to investigate AIV infections in falconers, their falconry birds as well as prey birds. Findings During 2 hunting seasons (2006/2007 and 2007/2008 falconers took tracheal and cloacal swabs from 1080 prey birds that were captured by their falconry birds (n = 54 in Germany. AIV-RNA of subtypes H6, H9, or H13 was detected in swabs of 4.1% of gulls (n = 74 and 3.8% of ducks (n = 53 using RT-PCR. The remaining 953 sampled prey birds and all falconry birds were negative. Blood samples of the falconry birds tested negative for AIV specific antibodies. Serum samples from all 43 falconers reacted positive in influenza A virus-specific ELISA, but remained negative using microneutralisation test against subtypes H5 and H7 and haemagglutination inhibition test against subtypes H6, H9 and H13. Conclusion Although we were able to detect AIV-RNA in samples from prey birds, the corresponding falconry birds and falconers did not become infected. Currently falconers do not seem to carry a high risk for getting infected with AIV through handling their falconry birds and their prey.

  3. The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis?

    Barba, Marta; Daly, Janet M

    2016-01-01

    Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1) has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon. Details are provided regarding what it is known about NS1 in equine influenza, especially concerning C-terminal truncation. Further research is needed to determine the role of NS1 in equine influenza infection, which will help to understand the pathophysiology of complicated cases related to cytokine imbalance and secondary bacterial infection, and to investigate new therapeutic and vaccination strategies. PMID:27589809

  4. Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

    Scull, Margaret A.; Gillim-Ross, Laura; Santos, Celia; Roberts, Kim L.; Bordonali, Elena; Subbarao, Kanta; Barclay, Wendy S.; Pickles, Raymond J.

    2009-01-01

    Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37°C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal ...

  5. Developments of Subunit and VLP Vaccines Against Influenza A Virus

    Ma-ping Deng; Zhi-hong Hu; Hua-lin Wang; Fei Deng

    2012-01-01

    Influenza virus is a continuous and severe global threat to mankind.The continuously re-emerging disease gives rise to thousands of deaths and enormous economic losses each year,which emphasizes the urgency and necessity to develop high-quality influenza vaccines in a safer,more efficient and economic way.The influenza subunit and VLP vaccines,taking the advantage of recombinant DNA technologies and expression system platforms,can be produced in such an ideal way.This review summarized the recent advancements in the research and development of influenza subunit and VLP vaccines based on the recombinant expression of hemagglutinin antigen (HA),neuraminidase antigen (NA),Matrix 2 protein (M2) and nucleocapsid protein (NP).It would help to get insight into the current stage of influenza vaccines,and suggest the future design and development of novel influenza vaccines.

  6. Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses.

    He, Yun; Yang, Yang; Iyer, Suri S

    2016-06-15

    We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). These unnatural sialosides were printed onto glass slides to generate a small focused microarray. We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. PMID:27139196

  7. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

    Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

    2016-01-01

    A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

  8. The global antigenic diversity of swine influenza A viruses

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky; Anderson, Tavis K; Berger, Kathryn; Bielejec, Filip; Burke, David F; Dudas, Gytis; Fonville, Judith M; Fouchier, Ron AM; Kellam, Paul; Koel, Bjorn F; Lemey, Philippe; Nguyen, Tung; Nuansrichy, Bundit; Peiris, JS Malik; Saito, Takehiko; Simon, Gaelle; Skepner, Eugene; Takemae, Nobuhiro; Webby, Richard J; Van Reeth, Kristien; Brookes, Sharon M; Larsen, Lars; Watson, Simon J; Brown, Ian H; Vincent, Amy L

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans. DOI: http://dx.doi.org/10.7554/eLife.12217.001 PMID:27113719

  9. The fast diagnosis by different methodologies of the influenza virus

    Iris Hatibi

    2013-09-01

    Full Text Available This paper presents the causative agent of the epidemic of the influenza in our country during the season 2009-2010. It also shows the effectiveness of the molecular diagnosis for Influenza virus by the means of the real-time PCR method in comparative of classical virological ones. Also in this paper we have presented the antigenic characterization of this virus which caused the pandemic during 2009-2010 years. We have collected and processed with several diagnostic methods like imunoflorescent assay, rapid tests, isolation and molecular method 409 samples. These were collected by the means of a Sentinel Surveillance throughout Albania, (tampon nasal- pharyngeal from people suspected of influenza in different ages. To isolate the virus of influenza we have used two methods: the method of isolation of influenza in the cell line of MDCK and also the isolation of the viral RNA by the means of the molecular method. The identifications of the isolates were carried out through the reactions of the hem agglutination inhibition and we have used also the method of Immunofluorescence and rapid test for the antigen detection of influenza virus. The results of the virus analyses are given in the relevant figures. The positive isolates were sent to the International Center of Influenza in London to be confirmed and also to have a further genetic analysis through molecular methods. From these tests performed during the season 2009-2010, it came out that our country was affected by one strain of influenza type A, AH1N1 variant A/California/2009/11. This strain circulated in the whole world causing the pandemic of 2009 and was a new variant deriving from the fusion of 4 strains of Influenza a process which occurred in pigs. These variants have affected the majority of the countries in Europe and in the world.

  10. Oseltamivir (Tamiflu® in the environment, resistance development in influenza A viruses of dabbling ducks and the risk of transmission of an oseltamivir-resistant virus to humans – a review

    Josef D. Järhult

    2012-06-01

    Full Text Available The antiviral drug oseltamivir (Tamiflu® is a cornerstone in influenza pandemic preparedness plans worldwide. However, resistance to the drug is a growing concern. The active metabolite oseltamivir carboxylate (OC is not degraded in surface water or sewage treatment plants and has been detected in river water during seasonal influenza outbreaks. The natural influenza reservoir, dabbling ducks, can thus be exposed to OC in aquatic environments. Environmental-like levels of OC induce resistance development in influenza A/H1N1 virus in mallards. There is a risk of resistance accumulation in influenza viruses circulating among wild birds when oseltamivir is used extensively. By reassortment or direct transmission, oseltamivir resistance can be transmitted to humans potentially causing a resistant pandemic or human-adapted highly-pathogenic avian influenza virus. There is a need for more research on resistance development in the natural influenza reservoir and for a prudent use of antivirals.

  11. El virus influenza y la gripe aviar Influenza virus and avian flu

    Libia Herrero-Uribe

    2008-01-01

    En este artículo se presenta una revisión del virus influenza,su biología,sus mecanismos de variación antigénica,las pandemias que ha producido y la prevención mediante las vacunas y medicamentos antivirales.Se analizan las razones por las cuales aparece el virus H5N1 que produce la fiebre aviar en humanos,la patogénesis de este virus y las estrategias para su prevención.Se informa sobre el plan de preparación para la pandemia en los niveles nacional e internacional.This article presents a re...

  12. Highly pathogenic avian influenza viruses inhibit effective immune responses of human blood-derived macrophages

    Friesenhagen, Judith; Boergeling, Yvonne; Hrincius, Eike; Ludwig, Stephan; Roth, Johannes; Viemann, Dorothee

    2012-01-01

    Human blood-derived macrophages are non-permissive for influenza virus propagation, and fail to elicit inflammatory and antiviral responses upon infection with high pathogenic avian influenza viruses.

  13. Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza Part II: Future compounds against influenza virus

    Gasparini, R; Amicizia, D.; Lai, P. L.; BRAGAZZI, N.L.; PANATTO, D.

    2014-01-01

    Summary In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential f...

  14. Selecting Viruses for the Seasonal Influenza Vaccine

    ... Japan (National Institute for Infectious Diseases); and Beijing, China (National Institute for Viral Disease Control and Prevention). ... Influenza (Flu) Vaccines Are Made . Top of Page Influenza Types Seasonal Avian Swine Variant Pandemic Other Get Email Updates To ...

  15. Panorama phylogenetic diversity and distribution of Type A influenza virus.

    Shuo Liu

    Full Text Available BACKGROUND: Type A influenza virus is one of important pathogens of various animals, including humans, pigs, horses, marine mammals and birds. Currently, the viral type has been classified into 16 hemagglutinin and 9 neuraminidase subtypes, but the phylogenetic diversity and distribution within the viral type largely remain unclear from the whole view. METHODOLOGY/PRINCIPAL FINDINGS: The panorama phylogenetic trees of influenza A viruses were calculated with representative sequences selected from approximately 23,000 candidates available in GenBank using web servers in NCBI and the software MEGA 4.0. Lineages and sublineages were classified according to genetic distances, topology of the phylogenetic trees and distributions of the viruses in hosts, regions and time. CONCLUSIONS/SIGNIFICANCE: Here, two panorama phylogenetic trees of type A influenza virus covering all the 16 hemagglutinin subtypes and 9 neuraminidase subtypes, respectively, were generated. The trees provided us whole views and some novel information to recognize influenza A viruses including that some subtypes of avian influenza viruses are more complicated than Eurasian and North American lineages as we thought in the past. They also provide us a framework to generalize the history and explore the future of the viral circulation and evolution in different kinds of hosts. In addition, a simple and comprehensive nomenclature system for the dozens of lineages and sublineages identified within the viral type was proposed, which if universally accepted, will facilitate communications on the viral evolution, ecology and epidemiology.

  16. Reverse Genetics Plasmid for Cloning Unstable Influenza A Virus Gene Segments

    Zhou, Bin; Jerzak, Greta; Scholes, Derek T.; Donnelly, Matthew E.; Li, Yan; Wentworth, David E.

    2011-01-01

    Reverse genetics approaches that enable the generation of recombinant influenza A viruses entirely from plasmids are invaluable for studies on virus replication, morphogenesis, pathogenesis, or transmission. Furthermore, influenza virus reverse genetics is now critical for the development of new vaccines for this human and animal pathogen. Periodically, influenza gene segments are unstable within plasmids in bacteria. The PB2 gene segment of a highly pathogenic avian H5 influenza virus A/Turk...

  17. Seroepidemiological Evidence of Avian Influenza A Virus Transmission to Pigs in Southern China

    Su, Shuo; Qi, Wenbao; Chen, Jidang; Zhu, Wanjun; Huang, Zhen; Xie, Jiexiong; Zhang, Guihong

    2013-01-01

    Recently, three novel avian-origin swine influenza viruses (SIVs) were first isolated from pigs in Guangdong Province, southern China, yet little is known about the seroprevalence of avian influenza viruses among pigs in southern China. Here, we report for the first time the seroprevalence of avian H3, H4, and H6 influenza viruses in swine populations and the lack of seroepidemiological evidence of avian H5 influenza virus transmission to pigs in China.

  18. Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin.

    Weaver, Eric A; Rubrum, Adam M; Webby, Richard J; Barry, Michael A

    2011-01-01

    Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 10(7) virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses. PMID:21464940

  19. Quantitative Risk Assessment of Avian Influenza Virus Infection via Water

    Schijven FJ; Teunis PFM; Roda Husman AM de; MGB

    2006-01-01

    Using literature data, daily infection risks of chickens and humans with H5N1 avian influenza virus (AIV) by drinking water consumption were estimated for the Netherlands. A highly infectious virus and less than 4 log10 drinking water treatment (reasonably inefficient) may lead to a high infection r

  20. DETECTION OF AVIAN INFLUENZA VIRUS USING AN INTERFEROMETRIC BIOSENSOR

    An optical interferometric waveguide immunoassay for direct and label-less detection of avian influenza virus is described. The assay response is based on index of refraction changes that occur upon binding of virus particles to antigen (hemagglutinin) specific antibodies on the waveguide surface. ...

  1. A new model for simulating evolution of human influenza virus

    2008-01-01

    @@ Understanding the evolution of influenza A virus, which poses a global challenge to public health, is of special significance for its control and prevention. Although the genome structure of the virus is seemingly simple, their evolutionary patterns and molecular mechanisms are difficult to reveal.

  2. Control of Influenza and Poliomyelitis with Killed Virus Vaccines

    Salk, Jonas; Salk, Darrell

    1977-01-01

    Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

  3. Influenza Virus Surveillance in Coordinated Swine Production Systems, United States.

    Kaplan, Bryan S; DeBeauchamp, Jennifer; Stigger-Rosser, Evelyn; Franks, John; Crumpton, Jeri Carol; Turner, Jasmine; Darnell, Daniel; Jeevan, Trushar; Kayali, Ghazi; Harding, Abbey; Webby, Richard J; Lowe, James F

    2015-10-01

    To clarify the epidemiology of influenza A viruses in coordinated swine production systems to which no animals from outside the system are introduced, we conducted virologic surveillance during September 2012-September 2013. Animal age, geographic location, and farm type were found to affect the prevalence of these viruses. PMID:26402228

  4. Immunohistochemical staining of avian influenza virus in tissues

    Immunohistochemical methods are commonly used for studying the pathogenesis of avian influenza (AI) virus by allowing the identification of sites of replication of the virus in infected tissues and the correlation with the histopathological changes observed. In this chapter, the materials and metho...

  5. Influenza and other respiratory viruses in three Central American countries

    Laguna‐Torres, Victor A.; Sánchez‐Largaespada, José F.; Lorenzana, Ivette; Forshey, Brett; Aguilar, Patricia; Jimenez, Mirna; Parrales, Eduardo; Rodriguez, Francisco; García, Josefina; Jimenez, Ileana; Rivera, Maribel; Perez, Juan; Sovero, Merly; Rios, Jane; Gamero, María E.; Halsey, Eric S.; Kochel, Tadeusz J.

    2010-01-01

    Please cite this paper as: Laguna‐Torres et al. (2011) Influenza and other respiratory viruses in three Central American countries. Influenza and Other Respiratory Viruses 5(2), 123–134. Background  Despite the disease burden imposed by respiratory diseases on children in Central America, there is a paucity of data describing the etiologic agents of the disease. Aims  To analyze viral etiologic agents associated with influenza‐like illness (ILI) in participants reporting to one outpatient health center, one pediatric hospital, and three general hospitals in El Salvador, Honduras, and Nicaragua Material & Methods  Between August 2006 and April 2009, pharyngeal swabs were collected from outpatients and inpatients. Patient specimens were inoculated onto cultured cell monolayers, and viral antigens were detected by indirect and direct immunofluorescence staining. Results  A total of 1,756 patients were enrolled, of whom 1,195 (68.3%) were under the age of 5; and 183 (10.4%) required hospitalization. One or more viral agents were identified in 434 (24.7%) cases, of which 17 (3.9%) were dual infections. The most common viruses isolated were influenza A virus (130; 7.4% of cases), respiratory syncytial virus (122; 6.9%), adenoviruses (63; 3.6%), parainfluenza viruses (57; 3.2%), influenza B virus (47; 2.7% of cases), and herpes simplex virus 1 (22; 1.3%). In addition, human metapneumovirus and enteroviruses (coxsackie and echovirus) were isolated from patient specimens. Discussion  When compared to the rest of the population, viruses were isolated from a significantly higher percentage of patients age 5 or younger. The prevalence of influenza A virus or influenza B virus infections was similar between the younger and older age groups. RSV was the most commonly detected pathogen in infants age 5 and younger and was significantly associated with pneumonia (p < 0.0001) and hospitalization (p < 0.0001). Conclusion  Genetic analysis of influenza

  6. Swine Influenza Viruses: a North American Perspective

    Influenza is a zoonotic viral disease that represents a health and economic threat to both humans and animals worldwide. Swine influenza was first recognized clinically in pigs in the Midwestern U.S. in 1918, coinciding with the human influenza pandemic known as the Spanish flu. Since that time swin...

  7. Within-host variation of avian influenza viruses

    Iqbal, Munir; Xiao, Hiaxia; Baillie, Greg; Warry, Andrew; Essen, Steve C.; Londt, Brandon; Brookes, Sharon M; Brown, Ian H.; McCauley, John W.

    2009-01-01

    The emergence and spread of H5N1 avian influenza viruses from Asia through to Europe and Africa pose a significant animal disease problem and have raised concerns that the virus may pose a pandemic threat to humans. The epizootological factors that have influenced the wide distribution of the virus are complex, and the variety of viruses currently circulating reflects these factors. Sequence analysis of the virus genes sheds light on the H5N1 virus evolution during its emergence and spread, b...

  8. Antibody Recognition of a Highly Conserved Influenza Virus Epitope

    Ekiert, Damian C.; Bhabha, Gira; Elsliger, Marc-André; Friesen, Robert H.E.; Jongeneelen, Mandy; Throsby, Mark; Goudsmit, Jaap; Wilson, Ian A.; Scripps; Crucell

    2009-05-21

    Influenza virus presents an important and persistent threat to public health worldwide, and current vaccines provide immunity to viral isolates similar to the vaccine strain. High-affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Cocrystal structures were determined at 2.2 and 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1 and HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.

  9. Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established.

    Nigel J Dimmock

    Full Text Available Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1. Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes.

  10. Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment

    Gabor, Kristin A.; Michelle F. Goody; Mowel, Walter K; Breitbach, Meghan E.; Gratacap, Remi L.; P. Eckhard Witten; Kim, Carol H.

    2014-01-01

    Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in substantial morbidity, mortality and economic burdens. Prevention and treatment of influenza illness is difficult due to the high mutation rate of the virus, the emergence of new virus strains and increasing antiviral resistance. Animal models of influenza infection are crucial to our gaining a better understanding of the pathogenesis of and host response to i...

  11. Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

    Belser, Jessica A; Blixt, Ola; Chen, Li-Mei; Pappas, Claudia; Maines, Taronna R; Van Hoeven, Neal; Donis, Ruben; Busch, Julia; McBride, Ryan; Paulson, James C; Katz, Jacqueline M; Tumpey, Terrence M

    2008-01-01

    viruses from The Netherlands in 2003 maintained the classic avian-binding preference for alpha2-3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses. However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the...... in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact. These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and...

  12. Chiropteran influenza viruses: flu from bats or a relic from the past?

    Brunotte, Linda; Beer, Martin; Horie, Masayuki; Schwemmle, Martin

    2016-02-01

    The identification of influenza A-like genomic sequences in bats suggests the existence of distinct lineages of chiropteran influenza viruses in South and Central America. These viruses share similarities with conventional influenza A viruses but lack the canonical receptor-binding property and neuraminidase function. The inability to isolate infectious bat influenza viruses impeded further studies, however, reverse genetic analysis provided new insights into the molecular biology of these viruses. In this review, we highlight the recent developments in the field of the newly discovered bat-derived influenza A-like viruses. We also discuss whether bats are a neglected natural reservoir of influenza viruses, the risk associated with bat influenza viruses for humans and whether these viruses originate from the pool of avian IAV or vice versa. PMID:26947779

  13. Novel Reassortant Highly Pathogenic Avian Influenza (H5N5) Viruses in Domestic Ducks, China

    Gu, Min; Liu, Wenbo; Cao, Yongzhong; Peng, Daxin; Wang, Xiaobo; Wan, Hongquan; Zhao, Guo; Xu, Quangang; Zhang, Wei; Song, Qingqing; Li, Yanfang; Liu, Xiufan

    2011-01-01

    In China, domestic ducks and wild birds often share the same water, in which influenza viruses replicate preferentially. Isolation of 2 novel reassortant highly pathogenic avian influenza (H5N5) viruses from apparently healthy domestic ducks highlights the role of these ducks as reassortment vessels. Such new subtypes of influenza viruses may pose a pandemic threat.

  14. Efficacy of Inactivated Swine Influenza Virus Vaccines Against 2009 H1N1 Influenza Virus in Pigs

    Introduction. The gene constellation of the 2009 pandemic H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species (1). Although its hemagglutinin gene is relat...

  15. Lack of chicken adaptation of newly emergent Eurasian H5N8 and reassortant H5N2 high pathogenicity avian influenza viruses in the U.S. is consistent with restricted poultry outbreaks in the Pacific flyway during 2014-2015.

    Bertran, Kateri; Swayne, David E; Pantin-Jackwood, Mary J; Kapczynski, Darrell R; Spackman, Erica; Suarez, David L

    2016-07-01

    In 2014-2015, the U.S. experienced an unprecedented outbreak of Eurasian clade 2.3.4.4 H5 highly pathogenic avian influenza (HPAI) virus, initially affecting mainly wild birds and few backyard and commercial poultry premises. To better model the outbreak, the pathogenesis and transmission dynamics of representative Eurasian H5N8 and reassortant H5N2 clade 2.3.4.4 HPAI viruses detected early in the North American outbreak were investigated in chickens. High mean chicken infectious doses and lack of seroconversion in survivors indicated the viruses were poorly chicken adapted. Pathobiological features were consistent with HPAI virus infection, although the delayed appearance of lesions, longer mean death times, and reduced replication in endothelial cells differed from features of most other Eurasian H5N1 HPAI viruses. Although these initial U.S. H5 HPAI viruses had reduced adaptation and transmissibility in chickens, multi-generational passage in poultry could generate poultry adapted viruses with higher infectivity and transmissibility. PMID:27110710

  16. Apoptosis in Raji cell line induced by influenza A virus

    李虹; 肖丽英; 李华林; 李婉宜; 蒋中华; 张林; 李明远

    2003-01-01

    Objective To study the apoptotic effects of influenza A virus on the Raji cell line. Methods Cultured Raji cells were infected with influenza A virus at a multiplicity of infection (m.o.i) of 20 and the effects of apoptosis were detected at different time points post infection using the following methods: electron microscope, DNA agarose gel electrophoresis, PI stained flow cytometry (FCM) and Annexin-V FITC/PI stained FCM.Results Raji cells infected with influenza A virus showed changes of morphology apoptotis, DNA agarose electrophoresis also demonstrated a ladder-like pattern of DNA fragments in a time-dependent manner. PI stained FCM showed "apoptosis peak" and FITC/PI stained FCM showed apoptotic cells. Quantitative analysis indicated that the percentage of apoptotic Raji cells increased after infection, and cycloheximide (CHX), an eukaryotic transcription inhibitor, could effectively inhibit the apoptotic effects of influenza A virus in vitro.Conclusions Influenza A virus can induce apoptosis in Raji cell line suggesting that it may lead to a potential method for tumor therapy.

  17. Detecting emerging transmissibility of avian influenza virus in human households.

    Michiel van Boven

    2007-07-01

    Full Text Available Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i the animal reservoir, (ii humans who were infected by animals (primary human-to-human transmission, or (iii humans who were infected by humans (secondary human-to-human transmission. Here we propose a method of analysing household infection data to detect changes in the transmissibility of avian influenza viruses in humans at an early stage. The method is applied to an outbreak of H7N7 avian influenza virus in The Netherlands that was the cause of more than 30 human-to-human transmission events. The analyses indicate that secondary human-to-human transmission is plausible for the Dutch household infection data. Based on the estimates of the within-household transmission parameters, we evaluate the effectiveness of antiviral prophylaxis, and conclude that it is unlikely that all household infections can be prevented with current antiviral drugs. We discuss the applicability of our method for the detection of emerging human-to-human transmission of avian influenza viruses in particular, and for the analysis of within-household infection data in general.

  18. Detailed Report on 2014/15 Influenza Virus Characteristics, and Estimates on Influenza Virus Vaccine Effectiveness from Austria’s Sentinel Physician Surveillance Network

    Redlberger-Fritz, Monika; Kundi, Michael; Popow-Kraupp, Theresia

    2016-01-01

    Background Influenza vaccine effectiveness (VE) is influenced by the antigenic similarity between vaccine- and circulating strains. Material and Methods This paper presents data obtained by the Austrian sentinel surveillance system on the evolution of influenza viruses during the season 2014/15 and its impact on influenza vaccine effectiveness in primary care in Austria as estimated by a test-negative case control design. VE estimates were performed for each influenza virus type/subtype, stra...

  19. Immunity to Pre-1950 H1N1 Influenza Viruses Confers Cross-Protection against the Pandemic Swine-Origin 2009 A (H1N1) Influenza Virus

    Skountzou, Ioanna; Koutsonanos, Dimitrios G.; Kim, Jin Hyang; Powers, Ryan; Satyabhama, Lakshmipriyadarshini; Masseoud, Feda; Weldon, William C.; Martin, Maria del Pilar; Mittler, Robert S.; Compans, Richard; Jacob, Joshy

    2010-01-01

    The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, 60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50–60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in ...

  20. Rapid Semiautomated Subtyping of Influenza Virus Species during the 2009 Swine Origin Influenza A H1N1 Virus Epidemic in Milwaukee, Wisconsin▿

    Bose, Michael E; Beck, Eric T.; Ledeboer, Nate; Kehl, Sue C.; Jurgens, Lisa A.; Patitucci, Teresa; Witt, Lorraine; LaGue, Elizabeth; Darga, Patrick; He, Jie; Fan, Jiang; Kumar, Swati; Kelly J. Henrickson

    2009-01-01

    In the spring of 2009, a novel influenza A (H1N1) virus (swine origin influenza virus [S-OIV]) emerged and began causing a large outbreak of illness in Milwaukee, WI. Our group at the Midwest Respiratory Virus Program laboratory developed a semiautomated real-time multiplex reverse transcription-PCR assay (Seasonal), employing the NucliSENS easyMAG system (bioMérieux, Durham, NC) and a Raider thermocycler (HandyLab Inc., Ann Arbor, MI), that typed influenza A virus, influenza B virus, and res...

  1. Evaluation of Jatropha curcas Linn. leaf extracts for its cytotoxicity and potential to inhibit hemagglutinin protein of influenza virus

    Patil, Deepak; Roy, Soumen; Dahake, Ritwik; Rajopadhye, Shreewardhan; Kothari, Sweta; Deshmukh, Ranjana; Chowdhary, Abhay

    2013-01-01

    Influenza is a serious respiratory illness which can be debilitating and cause complications that lead to hospitalization and death. Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. Given temporal and geographic changes and the shifts in antiviral drug resistance among influenza viruses, it is time to consider natural antiviral agents against influenza virus. Jatropha curcas is known for var...

  2. Anti-influenza virus effect of aqueous extracts from dandelion

    He Wen; Han Huamin; Wang Wei; Gao Bin

    2011-01-01

    Abstract Background Human influenza is a seasonal disease associated with significant morbidity and mortality. Anti-flu Traditional Chinese Medicine (TCM) has played a significant role in fighting the virus pandemic. In TCM, dandelion is a commonly used ingredient in many therapeutic remedies, either alone or in conjunction with other natural substances. Evidence suggests that dandelion is associated with a variety of pharmacological activities. In this study, we evaluated anti-influenza viru...

  3. Requirements of New Vaccines against Novel Influenza Viruses

    Kobayashi, Osamu

    2014-01-01

    The currently available influenza vaccines were developed in the 1930s through the 1960s using technologies that were state-of-the art for the times. Decades of advancement in virology and immunology have provided the tools for making better vaccines against influenza virus. Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe v...

  4. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Svetlana V Shcherbik

    Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  5. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Irina Margine

    2014-10-01

    Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.

  6. Multi-antigen vaccines based on complex adenovirus vectors induce protective immune responses against H5N1 avian influenza viruses.

    Holman, David H; Wang, Danher; Raja, Nicholas U; Luo, Min; Moore, Kevin M; Woraratanadharm, Jan; Mytle, Nutan; Dong, John Y

    2008-05-19

    There are legitimate concerns that the highly pathogenic H5N1 avian influenza virus could adapt for human-to-human transmission and cause a pandemic similar to the 1918 "Spanish flu" that killed 50 million people worldwide. We have developed pandemic influenza vaccines by incorporating multiple antigens from both avian and Spanish influenza viruses into complex recombinant adenovirus vectors. In vaccinated mice, these vaccines induced strong humoral and cellular immune responses against pandemic influenza virus antigens, and protected vaccinated mice against lethal H5N1 virus challenge. These results indicate that this multi-antigen, broadly protective vaccine may serve as a safer and more effective approach than traditional methods for development of a pandemic influenza vaccine. PMID:18395306

  7. Hsp90 inhibitors reduce influenza virus replication in cell culture

    The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses

  8. Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models.

    Belser, Jessica A; Eckert, Alissa M; Tumpey, Terrence M; Maines, Taronna R

    2016-09-01

    Ferrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses. PMID:27412880

  9. Well-tolerated Spirulina extract inhibits influenza virus replication and reduces virus-induced mortality

    Yi-Hsiang Chen; Gi-Kung Chang; Shu-Ming Kuo; Sheng-Yu Huang; I-Chen Hu; Yu-Lun Lo; Shin-Ru Shih

    2016-01-01

    Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts a...

  10. Serum amyloid P component binds to influenza A virus haemagglutinin and inhibits the virus infection in vitro

    Andersen, Ove; Vilsgaard Ravn, K; Juul Sørensen, I; Jonson, G; Holm Nielsen, E; Svehag, SE

    1997-01-01

    that SAP can bind to influenza A virus and inhibit agglutination of erythrocytes mediated by the virus subtypes H1N1, H2N2 and H3N2. SAP also inhibits the production of haemagglutinin (HA) an the cytopathogenic effect of influenza A virus in MDCK cells. The binding of SAP to the virus requires...

  11. Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses

    Holm, Christian K.; Rahbek, Stine H.; Gad, Hans Henrik; Bak, Rasmus O.; Jakobsen, Martin R; Jiang, Zhaozaho; Hansen, Anne Louise; Jensen, Simon K.; Sun, Chenglong; Thomsen, Martin K.; Laustsen, Anders; Nielsen, Camilla G.; Severinsen, Kasper; Xiong, Yingluo; Burdette, Dara L.

    2016-01-01

    Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserve...

  12. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    2003-01-01

    MedImmune Vaccines (formerly Aviron) has developed a cold-adapted live influenza virus vaccine [FluMist] that can be administered by nasal spray. FluMist is the first live virus influenza vaccine and also the first nasally administered vaccine to be marketed in the US. The vaccine will be formulated to contain live attenuated (att) influenza virus reassortants of the strains recommended by the US Public Health Service for each 'flu season. The vaccine is termed cold-adapted (ca) because the virus has been adapted to replicate efficiently at 25 degrees C in the nasal passages, which are below normal body temperature. The strains used in the seasonal vaccine will also be made temperature sensitive (ts) so that their replication is restricted at 37 degrees C (Type B strains) and 39 degrees C (Type A strains). The combined effect of the antigenic properties and the att, ca and ts phenotypes of the influenza strains contained in the vaccine enables the viruses to replicate in the nasopharynx to produce protective immunity. The original formulation of FluMist requires freezer storage throughout distribution. Because many international markets do not have distribution channels well suited to the sale of frozen vaccines, Wyeth and MedImmune are collaborating to develop a second generation, refrigerator-stable, liquid trivalent cold-adapted influenza vaccine (CAIV-T), which is in phase III trials. Initially, the frozen formulation will only be available in the US. For the 2003-2004 season, FluMist will contain A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) (A/Moscow/10/99-like) and B/Hong Kong/330/2001. Aviron was acquired by MedImmune on 15 January 2002. Aviron is now a wholly-owned subsidiary of MedImmune and is called MedImmune Vaccines. Aviron acquired FluMist in March 1995 through a Co-operative Research and Development Agreement (CRADA) with the US NIAID, and a licensing agreement with the University of Michigan, Ann Arbor, USA. In June 2000, the CRADA was

  13. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    Sun Young Yin; Hyoung Jin Kim; Hong-Jin Kim

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extr...

  14. The hemagglutinin structure of an avian H1N1 influenza A virus

    Lin, Tianwei; Wang, Gengyan; Li, Anzhang; Zhang, Qian; Wu, Caiming; Zhang, Rongfu; Cai, Qixu; Song, Wenjun; Yuen, Kwok-Yung; (U. Hong Kong); (Inter. Inst. Infect. Imm.); (Xiamen)

    2009-09-15

    The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptor binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.

  15. Novel avian influenza A (H7N9 virus induces impaired interferon responses in human dendritic cells.

    Veera Arilahti

    Full Text Available In March 2013 a new avian influenza A(H7N9 virus emerged in China and infected humans with a case fatality rate of over 30%. Like the highly pathogenic H5N1 virus, H7N9 virus is causing severe respiratory distress syndrome in most patients. Based on genetic analysis this avian influenza A virus shows to some extent adaptation to mammalian host. In the present study, we analyzed the activation of innate immune responses by this novel H7N9 influenza A virus and compared these responses to those induced by the avian H5N1 and seasonal H3N2 viruses in human monocyte-derived dendritic cells (moDCs. We observed that in H7N9 virus-infected cells, interferon (IFN responses were weak although the virus replicated as well as the H5N1 and H3N2 viruses in moDCs. H7N9 virus-induced expression of pro-inflammatory cytokines remained at a significantly lower level as compared to H5N1 virus-induced "cytokine storm" seen in human moDCs. However, the H7N9 virus was extremely sensitive to the antiviral effects of IFN-α and IFN-β in pretreated cells. Our data indicates that different highly pathogenic avian viruses may show considerable differences in their ability to induce host antiviral responses in human primary cell models such as moDCs. The unexpected appearance of the novel H7N9 virus clearly emphasizes the importance of the global influenza surveillance system. It is, however, equally important to systematically characterize in normal human cells the replication capacity of the new viruses and their ability to induce and respond to natural antiviral substances such as IFNs.

  16. Efficacy of canine influenza virus (H3N8) vaccine to decrease severity of clinical disease after co-challenge with canine influenza virus and Streptococcus equi subsp. Zooepidemicus

    Since first emerging into the North American canine population in 2004, canine influenza virus (CIV) subtype H3N8 has shown horizontal transmission among dogs, with a high level of adaptation to this species. Severity of disease is variable, and co-infection by other respiratory pathogens is an impo...

  17. Replication of avian, human and swine influenza viruses in porcine respiratory explants and association with sialic acid distribution

    Nauwynck Hans J

    2010-02-01

    Full Text Available Abstract Background Throughout the history of human influenza pandemics, pigs have been considered the most likely "mixing vessel" for reassortment between human and avian influenza viruses (AIVs. However, the replication efficiencies of influenza viruses from various hosts, as well as the expression of sialic acid (Sia receptor variants in the entire porcine respiratory tract have never been studied in detail. Therefore, we established porcine nasal, tracheal, bronchial and lung explants, which cover the entire porcine respiratory tract with maximal similarity to the in vivo situation. Subsequently, we assessed virus yields of three porcine, two human and six AIVs in these explants. Since our results on virus replication were in disagreement with the previously reported presence of putative avian virus receptors in the trachea, we additionally studied the distribution of sialic acid receptors by means of lectin histochemistry. Human (Siaα2-6Gal and avian virus receptors (Siaα2-3Gal were identified with Sambucus Nigra and Maackia amurensis lectins respectively. Results Compared to swine and human influenza viruses, replication of the AIVs was limited in all cultures but most strikingly in nasal and tracheal explants. Results of virus titrations were confirmed by quantification of infected cells using immunohistochemistry. By lectin histochemistry we found moderate to abundant expression of the human-like virus receptors in all explant systems but minimal binding of the lectins that identify avian-like receptors, especially in the nasal, tracheal and bronchial epithelium. Conclusions The species barrier that restricts the transmission of influenza viruses from one host to another remains preserved in our porcine respiratory explants. Therefore this system offers a valuable alternative to study virus and/or host properties required for adaptation or reassortment of influenza viruses. Our results indicate that, based on the expression of Sia

  18. The Timeline of Influenza Virus Shedding in Children and Adults in a Household Transmission Study of Influenza in Managua, Nicaragua.

    Ng, Sophia; Lopez, Roger; Kuan, Guillermina; Gresh, Lionel; Balmaseda, Angel; Harris, Eva; Gordon, Aubree

    2016-05-01

    In a household transmission study in Nicaragua, children under 6 years old had a longer duration of presymptomatic influenza virus shedding than adults. The duration of postsymptomatic influenza virus shedding was longest in children 0-5 years old, followed by children 6-15 years of age and adults. PMID:26910589

  19. Rapid preparation of mutated influenza hemagglutinins for influenza virus pandemic prevention.

    Nishioka, Ryosuke; Satomura, Atsushi; Yamada, Junki; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2016-03-01

    Influenza viruses have periodically caused pandemic due to frequent mutation of viral proteins. Influenza viruses have two major membrane glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin plays a crucial role in viral entry, while NA is involved in the process of a viral escape. In terms of developing antiviral drugs, HA is a more important target than NA in the prevention of pandemic, since HA is likely to change the host specificity of a virus by acquiring mutations, thereby to increase the risk of pandemic. To characterize mutated HA functions, current approaches require immobilization of purified HA on plastic wells and carriers. These troublesome methods make it difficult to respond to emerging mutations. In order to address this problem, a yeast cell surface engineering approach was investigated. Using this technology, human HAs derived from various H1N1 subtypes were successfully and rapidly displayed on the yeast cell surface. The yeast-displayed HAs exhibited similar abilities to native influenza virus HAs. Using this system, human HAs with 190E and 225G mutations were shown to exhibit altered recognition specificities from human to avian erythrocytes. This system furthermore allowed direct measurement of HA binding abilities without protein purification and immobilization. Coupled with the ease of genetic manipulation, this system allows the simple and comprehensive construction of mutant protein libraries on yeast cell surface, thereby contributing to influenza virus pandemic prevention. PMID:26797882

  20. Patterns of evolution and host gene mimicry in influenza and other RNA viruses.

    Benjamin D Greenbaum

    2008-06-01

    Full Text Available It is well known that the dinucleotide CpG is under-represented in the genomic DNA of many vertebrates. This is commonly thought to be due to the methylation of cytosine residues in this dinucleotide and the corresponding high rate of deamination of 5-methycytosine, which lowers the frequency of this dinucleotide in DNA. Surprisingly, many single-stranded RNA viruses that replicate in these vertebrate hosts also have a very low presence of CpG dinucleotides in their genomes. Viruses are obligate intracellular parasites and the evolution of a virus is inexorably linked to the nature and fate of its host. One therefore expects that virus and host genomes should have common features. In this work, we compare evolutionary patterns in the genomes of ssRNA viruses and their hosts. In particular, we have analyzed dinucleotide patterns and found that the same patterns are pervasively over- or under-represented in many RNA viruses and their hosts suggesting that many RNA viruses evolve by mimicking some of the features of their host's genes (DNA and likely also their corresponding mRNAs. When a virus crosses a species barrier into a different host, the pressure to replicate, survive and adapt, leaves a footprint in dinucleotide frequencies. For instance, since human genes seem to be under higher pressure to eliminate CpG dinucleotide motifs than avian genes, this pressure might be reflected in the genomes of human viruses (DNA and RNA viruses when compared to those of the same viruses replicating in avian hosts. To test this idea we have analyzed the evolution of the influenza virus since 1918. We find that the influenza A virus, which originated from an avian reservoir and has been replicating in humans over many generations, evolves in a direction strongly selected to reduce the frequency of CpG dinucleotides in its genome. Consistent with this observation, we find that the influenza B virus, which has spent much more time in the human population, has

  1. Novel Reassortant Influenza A(H5N8) Viruses in Domestic Ducks, Eastern China

    Wu, Haibo; Peng, Xiaorong; Xu, Lihua; Jin, Changzhong; Cheng, Linfang; Lu, Xiangyun; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

    2014-01-01

    Domestic ducks are natural reservoirs of avian influenza viruses and serve as reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8) viruses from domestic ducks in eastern China, sequenced their genomes, and tested their pathogenicity in chickens and mice. Circulation of these viruses may pose health risks for humans.

  2. Competition between influenza A virus genome segments.

    Ivy Widjaja

    Full Text Available Influenza A virus (IAV contains a segmented negative-strand RNA genome. How IAV balances the replication and transcription of its multiple genome segments is not understood. We developed a dual competition assay based on the co-transfection of firefly or Gaussia luciferase-encoding genome segments together with plasmids encoding IAV polymerase subunits and nucleoprotein. At limiting amounts of polymerase subunits, expression of the firefly luciferase segment was negatively affected by the presence of its Gaussia luciferase counterpart, indicative of competition between reporter genome segments. This competition could be relieved by increasing or decreasing the relative amounts of firefly or Gaussia reporter segment, respectively. The balance between the luciferase expression levels was also affected by the identity of the untranslated regions (UTRs as well as segment length. In general it appeared that genome segments displaying inherent higher expression levels were more efficient competitors of another segment. When natural genome segments were tested for their ability to suppress reporter gene expression, shorter genome segments generally reduced firefly luciferase expression to a larger extent, with the M and NS segments having the largest effect. The balance between different reporter segments was most dramatically affected by the introduction of UTR panhandle-stabilizing mutations. Furthermore, only reporter genome segments carrying these mutations were able to efficiently compete with the natural genome segments in infected cells. Our data indicate that IAV genome segments compete for available polymerases. Competition is affected by segment length, coding region, and UTRs. This competition is probably most apparent early during infection, when limiting amounts of polymerases are present, and may contribute to the regulation of segment-specific replication and transcription.

  3. Influenza virus transmission is dependent on relative humidity and temperature.

    Anice C Lowen

    2007-10-01

    Full Text Available Using the guinea pig as a model host, we show that aerosol spread of influenza virus is dependent upon both ambient relative humidity and temperature. Twenty experiments performed at relative humidities from 20% to 80% and 5 degrees C, 20 degrees C, or 30 degrees C indicated that both cold and dry conditions favor transmission. The relationship between transmission via aerosols and relative humidity at 20 degrees C is similar to that previously reported for the stability of influenza viruses (except at high relative humidity, 80%, implying that the effects of humidity act largely at the level of the virus particle. For infected guinea pigs housed at 5 degrees C, the duration of peak shedding was approximately 40 h longer than that of animals housed at 20 degrees C; this increased shedding likely accounts for the enhanced transmission seen at 5 degrees C. To investigate the mechanism permitting prolonged viral growth, expression levels in the upper respiratory tract of several innate immune mediators were determined. Innate responses proved to be comparable between animals housed at 5 degrees C and 20 degrees C, suggesting that cold temperature (5 degrees C does not impair the innate immune response in this system. Although the seasonal epidemiology of influenza is well characterized, the underlying reasons for predominant wintertime spread are not clear. We provide direct, experimental evidence to support the role of weather conditions in the dynamics of influenza and thereby address a long-standing question fundamental to the understanding of influenza epidemiology and evolution.

  4. Perspective of Use of Antiviral Peptides against Influenza Virus.

    Skalickova, Sylvie; Heger, Zbynek; Krejcova, Ludmila; Pekarik, Vladimir; Bastl, Karel; Janda, Jozef; Kostolansky, Frantisek; Vareckova, Eva; Zitka, Ondrej; Adam, Vojtech; Kizek, Rene

    2015-10-01

    The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides. PMID:26492266

  5. Perspective of Use of Antiviral Peptides against Influenza Virus

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  6. Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin

    Shuwen Liu

    2013-01-01

    Full Text Available Influenza A virus (IAV has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA, the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.

  7. Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections

    Furuya-Kanamori, Luis; Cox, Mitchell; Milinovich, Gabriel J.; Magalhaes, Ricardo J. Soares; Mackay, Ian M.

    2016-01-01

    Influenza infection manifests in a wide spectrum of severity, including symptomless pathogen carriers. We conducted a systematic review and meta-analysis of 55 studies to elucidate the proportional representation of these asymptomatic infected persons. We observed extensive heterogeneity among these studies. The prevalence of asymptomatic carriage (total absence of symptoms) ranged from 5.2% to 35.5% and subclinical cases (illness that did not meet the criteria for acute respiratory or influenza-like illness) from 25.4% to 61.8%. Statistical analysis showed that the heterogeneity could not be explained by the type of influenza, the laboratory tests used to detect the virus, the year of the study, or the location of the study. Projections of infection spread and strategies for disease control require that we identify the proportional representation of these insidious spreaders early on in the emergence of new influenza subtypes or strains and track how this rate evolves over time and space. PMID:27191967

  8. Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

    Fordyce, Sarah L; Bragstad, Karoline; Pedersen, Svend Stenvang; Jensen, Thøger Gorm; Gahrn-Hansen, Bente; Daniels, Rod; Hay, Alan; Kampmann, Marie-Louise; Bruhn, Christian Aw; Moreno-Mayar, J Victor; Avila Arcos, Maria del Carmen; Gilbert, M Thomas P; Nielsen, Lars P

    2013-01-01

    Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly...

  9. A quantitative comet infection assay for influenza virus

    Lindsay, Stephen M.; Timm, Andrea; Yin, John

    2011-01-01

    The virus comet assay is a cell-based virulence assay used to evaluate an antiviral drug or antibody against a target virus. The comet assay differs from the plaque assay in allowing spontaneous flows in 6-well plates to spread virus. When implemented quantitatively the comet assay has been shown to have an order-of-magnitude greater sensitivity to antivirals than the plaque assay. In this study, a quantitative comet assay for influenza virus is demonstrated, and is shown to have a 13-fold in...

  10. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice

    Reading Patrick C

    2008-08-01

    Full Text Available Abstract Background Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. Methods The anti-Gr-1 monoclonal antibody (mAb RB6-8C5 was used to (i identify neutrophils in the upper (nasal tissues and lower (lung respiratory tract of uninfected and influenza virus-infected mice, and (ii deplete neutrophils prior to and during influenza virus infection of mice. Results Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6 mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. Conclusion Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response.

  11. H5N6 influenza virus infection, the newest influenza

    Beuy; Joob; Wiwanitkit; Viroj

    2015-01-01

    The most recent new emerging infection is the H5N6 inl uenza virus infection. This infection has just been reported from China in early May 2014. The disease is believed to be a cross species infection. All indexed cases are from China. Of interest, the H5N6 inl uenza virus is the primary virus for avian. The avian H5N6 inl uenza virus in avian population is a low virulent strain. However, the clinical manifestation in human seems severe. In this mini-review, the authors summarize and discuss on this new emerging inl uenza.

  12. Evolutionary and transmission dynamics of reassortant H5N1 influenza virus in Indonesia.

    Tommy Tsan-Yuk Lam

    Full Text Available H5N1 highly pathogenic avian influenza (HPAI viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses.

  13. Los virus Influenza y la nueva pandemia A/H1N1

    Miguel Talledo; Kattya Zumaeta

    2011-01-01

    Los virus Influenza pertenecen a la familia Orthomyxoviridae, virus con genoma RNA de sentido negativo segmentado. Los virus influenza tipo A infectan a humanos y otros organismos, y son los agentes causantes de influenza en humanos. Resaltan entre sus principales proteínas la Hemaglutinina y la Neuraminidasa, que son utilizadas en la clasificación de los miembros de este grupo. Estos virus mutan continuamente, exhibiendo patrones muy estudiados, como el cambio y la deriva antigénica, siendo ...

  14. Genetic characterization of highly pathogenic H5 influenza viruses from poultry in Taiwan, 2015.

    Huang, Pei-Yu; Lee, Chang-Chun David; Yip, Chun-Hung; Cheung, Chung-Lam; Yu, Guangchuang; Lam, Tommy Tsan-Yuk; Smith, David K; Zhu, Huachen; Guan, Yi

    2016-03-01

    Phylogenetic analysis of the highly pathogenic avian influenza (HPAI) H5 viruses causing recent outbreaks in Taiwan showed that they belonged to the Asian HPAI H5 lineage, clade 2.3.4.4 viruses, and were apparently introduced by migratory birds. These viruses reassorted with Eurasian influenza gene pool viruses and formed five genotypic variants. As Taiwan has a similar influenza ecosystem to southern China, the HPAI H5 lineage could become established and enzootic in the island. PMID:26690663

  15. Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses.

    Hoffmann, Bernd; Hoffmann, Donata; Henritzi, Dinah; Beer, Martin; Harder, Timm C

    2016-01-01

    Rapid and sensitive diagnostic approaches are of the utmost importance for the detection of humans and animals infected by specific influenza virus subtype(s). Cascade-like diagnostics starting with the use of pan-influenza assays and subsequent subtyping devices are normally used. Here, we demonstrated a novel low density array combining 32 TaqMan(®) real-time RT-PCR systems in parallel for the specific detection of the haemagglutinin (HA) and neuraminidase (NA) subtypes of avian and porcine hosts. The sensitivity of the newly developed system was compared with that of the pan-influenza assay, and the specificity of all RT-qPCRs was examined using a broad panel of 404 different influenza A virus isolates representing 45 different subtypes. Furthermore, we analysed the performance of the RT-qPCR assays with diagnostic samples obtained from wild birds and swine. Due to the open format of the array, adaptations to detect newly emerging influenza A virus strains can easily be integrated. The RITA array represents a competitive, fast and sensitive subtyping tool that requires neither new machinery nor additional training of staff in a lab where RT-qPCR is already established. PMID:27256976

  16. Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses

    Hoffmann, Bernd; Hoffmann, Donata; Henritzi, Dinah; Beer, Martin; Harder, Timm C.

    2016-01-01

    Rapid and sensitive diagnostic approaches are of the utmost importance for the detection of humans and animals infected by specific influenza virus subtype(s). Cascade-like diagnostics starting with the use of pan-influenza assays and subsequent subtyping devices are normally used. Here, we demonstrated a novel low density array combining 32 TaqMan® real-time RT-PCR systems in parallel for the specific detection of the haemagglutinin (HA) and neuraminidase (NA) subtypes of avian and porcine hosts. The sensitivity of the newly developed system was compared with that of the pan-influenza assay, and the specificity of all RT-qPCRs was examined using a broad panel of 404 different influenza A virus isolates representing 45 different subtypes. Furthermore, we analysed the performance of the RT-qPCR assays with diagnostic samples obtained from wild birds and swine. Due to the open format of the array, adaptations to detect newly emerging influenza A virus strains can easily be integrated. The RITA array represents a competitive, fast and sensitive subtyping tool that requires neither new machinery nor additional training of staff in a lab where RT-qPCR is already established. PMID:27256976

  17. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  18. Influenza A virus in pigs – protection, provocation and predisposition

    Endemic strains of influenza A virus (IAV) in North America pigs consist of the subtypes H1N1, H1N2, and H3N2. These circulating strains contain the triple reassortant internal gene (TRIG) cassette resulting from incorporation of genes from swine, avian, and human IAV's. Genetic drift and reassortme...

  19. Influenza virus induces bacterial and nonbacterial otitis media.

    Short, K.R.; Diavatopoulos, D.A.; Thornton, R.; Pedersen, J.; Strugnell, R.A.; Wise, A.K.; Reading, P.C.; Wijburg, O.L.

    2011-01-01

    Otitis media (OM) is one of the most common childhood diseases. OM can arise when a viral infection enables bacteria to disseminate from the nasopharynx to the middle ear. Here, we provide the first infant murine model for disease. Mice coinfected with Streptococcus pneumoniae and influenza virus ha

  20. Protective effect of dietary xylitol on influenza A virus infection.

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  1. Oligonucleotide microchip for subtyping of influenza A virus

    Fesenko, Eugeny E.; Kireyev, Dmitry E.; Gryadunov, Dmitry A.; Mikhailovich, Vladimir M.; Grebennikova, Tatyana V.; L’vov, Dmitry K.; Zasedatelev, Alexander S.

    2007-01-01

    Background  Influenza A viruses are classified into subtypes depending on the antigenic properties of their two outer glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Sixteen subtypes of HA and nine of NA are known. Lately, the circulation of some subtypes (H7N7, H5N1) has been closely watched because of the epidemiological threat they present. Objectives  This study assesses the potential of using gel‐based microchip technology for fast and sensitive molecular subtyping of the influenza A virus. Methods  The method employs a microchip of 3D gel‐based elements containing immobilized probes. Segments of the HA and NA genes are amplified using multiplex RT‐PCR and then hybridized with the microchip. Results  The developed microchip was validated using a panel of 21 known reference strains of influenza virus. Selected strains represented different HA and NA subtypes derived from avian, swine and human hosts. The whole procedure takes 10 hours and enables one to identify 15 subtypes of HA and two subtypes of NA. Forty‐one clinical samples isolated during the poultry fall in Novosibirsk (Russia, 2005) were successfully identified using the proposed technique. The sensitivity and specificity of the method were 76% and 100%, respectively, compared with the ‘gold standard’ techniques (virus isolation with following characterization by immunoassay). Conclusions  We conclude that the method of subtyping using gel‐based microchips is a promising approach for fast detection and identification of influenza A, which may greatly improve its monitoring. PMID:19453417

  2. Protective effect of dietary xylitol on influenza A virus infection.

    Sun Young Yin

    Full Text Available Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1. We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases.

  3. [Purification of neuraminidase from influenza virus on an immunosorbent].

    Iakubov, L A; Savich, I M; Beklemishev, A B

    1984-10-01

    A procedure for isolation of neuraminidase from influenza virus using the nonionic detergent Triton x-100 was developed. To achieve further purification, the protein mixture was passed through a Sepharose column packed with immobilized antibodies against hemagglutinin. The neuraminidase preparation thus obtained fully retained its enzymatic and antigenic properties and during electrophoretic separation under denaturating conditions gave one protein band. PMID:6440594

  4. Perspective of Use of Antiviral Peptides against Influenza Virus

    Skaličková, S.; Heger, Z.; Krejčová, L.; Pekárik, V.; Bastl, K.; Janda, Jozef; Kostolanský, F.; Varečková, E.; Zítka, O.; Adam, V.; Kizek, R.

    2015-01-01

    Roč. 7, č. 10 (2015), s. 5428-5442. ISSN 1999-4915 R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : cationic peptides * hemagglutinin * influenza virus Subject RIV: EC - Immunology Impact factor: 3.353, year: 2014

  5. Influenza A virus and secondary bacterial infection in swine

    Influenza A virus (IAV) infection alone causes significant disease characterized by respiratory distress and poor growth in pigs. Endemic strains of IAV in North America pigs consist of the subtypes H1N1, H1N2, and H3N2. These circulating strains contain the triple reassortant internal gene (TRIG) c...

  6. Highly pathogenic avian influenza virus among wild birds in Mongolia

    The central Asian country of Mongolia supports large populations of migratory water birds that migrate across much of Asia where highly pathogenic avian influenza (HPAI) virus subtype H5N1 is endemic. This, together with the near absence of domestic poultry, makes Mongolia an ideal location to unde...

  7. Characterization of the glycoproteins of bat-derived influenza viruses.

    Maruyama, Junki; Nao, Naganori; Miyamoto, Hiroko; Maeda, Ken; Ogawa, Hirohito; Yoshida, Reiko; Igarashi, Manabu; Takada, Ayato

    2016-01-15

    Recently found bat-derived influenza viruses (BatIVs) have hemagglutinin (HA) and neuraminidase (NA) gene segments distinct from those of previously known influenza A viruses. However, pathogenicities of these BatIVs remain unknown since infectious virus strains have not been isolated yet. To gain insight into the biological properties of BatIVs, we generated vesicular stomatitis viruses (VSVs) pseudotyped with the BatIV HA and NA. We found that VSVs pseudotyped with BatIV HAs and NAs efficiently infected particular bat cell lines but not those derived from primates, and that proteolytic cleavage with a trypsin-like protease was necessary for HA-mediated virus entry. Treatment of the susceptible bat cells with some enzymes and inhibitors revealed that BatIV HAs might recognize some cellular glycoproteins as receptors rather than the sialic acids used for the other known influenza viruses. These data provide fundamental information on the mechanisms underlying the cellular entry and host restriction of BatIVs. PMID:26605499

  8. Active NF-kappaB signalling is a prerequisite for influenza virus infection.

    Nimmerjahn, Falk; Dudziak, Diana; Dirmeier, Ulrike; Hobom, Gerd; Riedel, Alexander; Schlee, Martin; Staudt, Louis M; Rosenwald, Andreas; Behrends, Uta; Bornkamm, Georg W; Mautner, Josef

    2004-08-01

    Influenza virus still poses a major threat to human health. Despite widespread vaccination programmes and the development of drugs targeting essential viral proteins, the extremely high mutation rate of influenza virus still leads to the emergence of new pathogenic virus strains. Therefore, it has been suggested that cellular cofactors that are essential for influenza virus infection might be better targets for antiviral therapy. It has previously been reported that influenza virus efficiently infects Epstein-Barr virus-immortalized B cells, whereas Burkitt's lymphoma cells are virtually resistant to infection. Using this cellular system, it has been shown here that an active NF-kappaB signalling pathway is a general prerequisite for influenza virus infection of human cells. Cells with low NF-kappaB activity were resistant to influenza virus infection, but became susceptible upon activation of NF-kappaB. In addition, blocking of NF-kappaB activation severely impaired influenza virus infection of otherwise highly susceptible cells, including the human lung carcinoma cell lines A549 and U1752 and primary human cells. On the other hand, infection with vaccinia virus was not dependent on an active NF-kappaB signalling pathway, demonstrating the specificity of this pathway for influenza virus infection. These results might be of major importance for both the development of new antiviral therapies and the understanding of influenza virus biology. PMID:15269376

  9. High-throughput detection method for influenza virus.

    Kumar, Pawan; Bartoszek, Allison E; Moran, Thomas M; Gorski, Jack; Bhattacharyya, Sanjib; Navidad, Jose F; Thakar, Monica S; Malarkannan, Subramaniam

    2012-01-01

    Influenza virus is a respiratory pathogen that causes a high degree of morbidity and mortality every year in multiple parts of the world. Therefore, precise diagnosis of the infecting strain and rapid high-throughput screening of vast numbers of clinical samples is paramount to control the spread of pandemic infections. Current clinical diagnoses of influenza infections are based on serologic testing, polymerase chain reaction, direct specimen immunofluorescence and cell culture (1,2). Here, we report the development of a novel diagnostic technique used to detect live influenza viruses. We used the mouse-adapted human A/PR/8/34 (PR8, H1N1) virus (3) to test the efficacy of this technique using MDCK cells (4). MDCK cells (10(4) or 5 x 10(3) per well) were cultured in 96- or 384-well plates, infected with PR8 and viral proteins were detected using anti-M2 followed by an IR dye-conjugated secondary antibody. M2 (5) and hemagglutinin (1) are two major marker proteins used in many different diagnostic assays. Employing IR-dye-conjugated secondary antibodies minimized the autofluorescence associated with other fluorescent dyes. The use of anti-M2 antibody allowed us to use the antigen-specific fluorescence intensity as a direct metric of viral quantity. To enumerate the fluorescence intensity, we used the LI-COR Odyssey-based IR scanner. This system uses two channel laser-based IR detections to identify fluorophores and differentiate them from background noise. The first channel excites at 680 nm and emits at 700 nm to help quantify the background. The second channel detects fluorophores that excite at 780 nm and emit at 800 nm. Scanning of PR8-infected MDCK cells in the IR scanner indicated a viral titer-dependent bright fluorescence. A positive correlation of fluorescence intensity to virus titer starting from 10(2)-10(5) PFU could be consistently observed. Minimal but detectable positivity consistently seen with 10(2)-10(3) PFU PR8 viral titers demonstrated the high

  10. Measurement of airborne influenza virus during hen slaughtering in an ABSL-3E bioBUBBLE®

    Several avian viral diseases, including avian influenza, Newcastle disease, infectious bronchitis or laryngotracheitis, are transmitted via respiratory droplets or by contact with contaminated fomites. Using high pathogenicity avian influenza (HPAI) virus as a model, the objective of the present st...

  11. New England harbor seal H3N8 influenza virus retains avian-like receptor specificity.

    Hussein, Islam T M; Krammer, Florian; Ma, Eric; Estrin, Michael; Viswanathan, Karthik; Stebbins, Nathan W; Quinlan, Devin S; Sasisekharan, Ram; Runstadler, Jonathan

    2016-01-01

    An influenza H3N8 virus, carrying mammalian adaptation mutations, was isolated from New England harbor seals in 2011. We sought to assess the risk of its human transmissibility using two complementary approaches. First, we tested the binding of recombinant hemagglutinin (HA) proteins of seal H3N8 and human-adapted H3N2 viruses to respiratory tissues of humans and ferrets. For human tissues, we observed strong tendency of the seal H3 to bind to lung alveoli, which was in direct contrast to the human-adapted H3 that bound mainly to the trachea. This staining pattern was also consistent in ferrets, the primary animal model for human influenza pathogenesis. Second, we compared the binding of the recombinant HAs to a library of 610 glycans. In contrast to the human H3, which bound almost exclusively to α-2,6 sialylated glycans, the seal H3 bound preferentially to α-2,3 sialylated glycans. Additionally, the seal H3N8 virus replicated in human lung carcinoma cells. Our data suggest that the seal H3N8 virus has retained its avian-like receptor binding specificity, but could potentially establish infection in human lungs. PMID:26888262

  12. Detection of Influenza and Other Respiratory Viruses Carried Out in the Influenza Project - Monitoring Vaccine Effectiveness (I-MOVE).

    Woźniak-Kosek, Agnieszka

    2015-01-01

    The project Influenza Vaccine Effectiveness-Monitoring (I-MOVE) is part of the European research carried out by the ECDC (European Center for Disease Prevention and Control), aimed at monitoring the effectiveness of vaccination in Europe during the growing incidence of flu and influenza-like illnesses in the coming epidemic seasons. Laboratory studies using molecular RT-PCR biology methods for detection of genetic material of influenza virus and other respiratory viruses were performed by Voivodeship Sanitary-Epidemiological Stations in Poland. The validation of the results of swabs taken from the nose and throat were carried out in the Department of Influenza Research, National Influenza Center in Warsaw. The study involved 210 samples from patients across Poland. Positive results were recorded for 72.4 % of the samples; influenza virus type A was detected in 43 and type B in 38 cases, whereas in 71 cases other respiratory viruses were detected, which included Human parainfluenza virus type 1-4; Human respiratory syncytial virus type A and B; Human coronavirus 229E/NL63, OC43; Human rhinovirus type A, B, and C; Human enterovirus; and Human adenovirus. The results show that although influenza viruses predominated in the 2010/2011 season in Poland, other flu-like viruses also abounded. PMID:25252895

  13. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E.; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I.; Abad, Francesc X.; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert

    2010-01-01

    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus curren...

  14. Anti-influenza virus effect of aqueous extracts from dandelion

    He Wen

    2011-12-01

    Full Text Available Abstract Background Human influenza is a seasonal disease associated with significant morbidity and mortality. Anti-flu Traditional Chinese Medicine (TCM has played a significant role in fighting the virus pandemic. In TCM, dandelion is a commonly used ingredient in many therapeutic remedies, either alone or in conjunction with other natural substances. Evidence suggests that dandelion is associated with a variety of pharmacological activities. In this study, we evaluated anti-influenza virus activity of an aqueous extract from dandelion, which was tested for in vitro antiviral activity against influenza virus type A, human A/PR/8/34 and WSN (H1N1. Results Results obstained using antiviral assays, minigenome assay and real-time reverse transcription-PCR analysis showed that 0.625-5 mg/ml of dandelion extracts inhibited infections in Madin-Darby canine kidney (MDCK cells or Human lung adenocarcinoma cell line (A549 of PR8 or WSN viruses, as well as inhibited polymerase activity and reduced virus nucleoprotein (NP RNA level. The plant extract did not exhibit any apparent negative effects on cell viability, metabolism or proliferation at the effective dose. This result is consistent with the added advantage of lacking any reported complications of the plant's utility in traditional medicine over several centuries. Conclusion The antiviral activity of dandelion extracts indicates that a component or components of these extracts possess anti-influenza virus properties. Mechanisms of reduction of viral growth in MDCK or A549 cells by dandelion involve inhibition on virus replication.

  15. The Character of Influenza Virus the H7 Subtype and Alert to Novel Influenza Virus H7N9 Subtype Virus

    NLP Indi Dharmayanti

    2013-08-01

    Full Text Available Influenza virus subtype H7 influenza viruses as well as other influenza virus geographically divided into two distinct genetic lineages, North American (H7N2, H7N3 or Eurasian (H7N7 and H7N3. Unlike the AI virus subtypes H5, since 1997 until now, all the infections caused by the H5 virus has Neuraminidase subtype 1 but H7 subtype of AI virus that transmitted successfully to humans have variety of Neuraminidase, so it seems compatible with H7 subtype. In poultry, the H7 subtype of AI virus typically causes mild symptoms, although there are also several outbreaks caused by this subtype virus, so it did not cause panic and active surveillance activities to identify this virus. It is very different from the H5N1 virus which caused many deaths and losses in poultry that infected with H5N1 virus so that it can be identified quickly. In April 2013, China reported a new AI virus is novel H7N9 which resulted in several people died. The world became aware of the H7N9 virus spreading to outside from China, it takes vigilance to be able to anticipate the disease, including Indonesia. Analysis of novel H7N9 virus showed that all genes of the virus is of avian origin, and the three other genes of the virus are reassorment from six internal genes of the AI virus A (H9N2 A/brambling/Beijing/16/2012, HA gene derived from A/duck/Zhejiang/12/2011 (H7N3, and NA genes thought to have come from A/wildbird/Korea/A14/2011 (H7N9. Epidemiological studies show that 77% of people infected by H7N9 have direct or indirect contact with animals including poultry when visiting or working in live poultry markets. Novel H7N9 virus was also found in pigeons, chickens, and environmental that have high genetic similarities with the novel H7N9 virus that infects humans. Until now (May 2013, a novel H7N9 virus has not been identified in Indonesia, so as a precaution and because the symptoms caused by the H7N9 virus is not visible (mild symptom in poultry so that the necessary actions

  16. Novel reassortant highly pathogenic H5N2 avian influenza viruses in poultry in China.

    Guo Zhao

    Full Text Available There has been multiple evidence that domestic poultry may act as a vessel for the generation of novel influenza A viruses. In this study, we have analyzed the evolution and pathogenicity of 4 H5N2 avian influenza viruses isolated from apparently healthy poultry from H5N1 virus endemic areas in China. Phylogenetic analysis revealed that two of these viruses, A/duck/Eastern China/1111/2011 (DK/EC/1111/11 and A/goose/Eastern China/1112/2011 (GS/EC/1112/11 were derived from reassortment events in which clade 2.3.4 highly pathogenic avian influenza (HPAI H5N1 viruses acquired novel neuraminidase and nonstructural protein genes. Another two isolates, A/chicken/Hebei/1102/2010 (CK/HB/1102/10 and A/duck/Hebei/0908/2009 (DK/HB/0908/09, possess hemagglutinin (HA gene belong to clade 7 H5 viruses and other genes from endemic H9N2 viruses, or from viruses of various subtypes of the natural gene pool. All of these H5N2 isolates bear characteristic sequences of HPAI virus at the cleavage site of HA, and animal experiments indicated that all of these viruses but DK/HB/0908/09 is highly pathogenic to chickens. In particular, DK/EC/1111/11 and GS/EC/1112/11 are also highly pathogenic to ducks and moderately pathogenic to mice. All of these 4 viruses were able to replicate in domestic ducks and mice without prior adaptation. The emergence of these novel H5N2 viruses adds more evidence for the active evolution of H5 viruses in Asia. The maintenance of the highly pathogenic phenotype of some of these viruses even after reassortment with a new NA subtypes, their ability to replicate and transmit in domestic poultry, and the pathogenicity in the mammalian mouse model, highlight the potential threat posed by these viruses to both veterinary and public health.

  17. The immune profile associated with acute allergic asthma accelerates clearance of influenza virus

    Samarasinghe, Amali E.; Woolard, Stacie N; Boyd, Kelli L.; Hoselton, Scott A; Schuh, Jane M; McCullers, Jonathan A.

    2014-01-01

    Asthma was the most common comorbidity in hospitalized patients during the 2009 influenza pandemic. For unknown reasons, hospitalized asthmatics had less severe outcomes and were less likely to die from pandemic influenza. Our data with primary human bronchial cells indicate that changes intrinsic to epithelial cells in asthma may protect against cytopathology induced by influenza virus. To further study influenza virus pathogenesis in allergic hosts, we aimed to develop and characterize muri...

  18. Survey of influenza and other respiratory viruses diagnostic testing in US hospitals, 2012–2013

    Su, Su; Fry, Alicia M.; Kirley, Pam Daily; Aragon, Deborah; Yousey‐Hindes, Kimberly; Meek, James; Openo, Kyle; Oni, Oluwakemi; Sharangpani, Ruta; Morin, Craig; Hollick, Gary; Lung, Krista; Laidler, Matt; Lindegren, Mary Lou; Schaffner, William

    2016-01-01

    Background Little is known about laboratory capacity to routinely diagnose influenza and other respiratory viruses at clinical laboratories and hospitals. Aims We sought to assess diagnostic practices for influenza and other respiratory virus in a survey of hospitals and laboratories participating in the US Influenza Hospitalization Surveillance Network in 2012–2013. Materials and Methods All hospitals and their associated laboratories participating in the Influenza Hospitalization Surveillan...

  19. The Analysis of B-Cell Epitopes of Influenza Virus Hemagglutinin

    Shcherbinin, D.N.; S. V Alekseeva; Shmarov, M.M.; Smirnov, Yu.A.; Naroditskiy, B.S.; Gintsburg, A.L.

    2016-01-01

    Vaccination has been successfully used to prevent influenza for a long time. Influenza virus hemagglutinin (HA), which induces a humoral immune response in humans and protection against the flu, is the main antigenic component of modern influenza vaccines. However, new seasonal and pandemic influenza virus variants with altered structures of HA occasionally occur. This allows the pathogen to avoid neutralization with antibodies produced in response to previous vaccination. Development of a va...

  20. THE ANALYSIS OF B-CELL EPITOPES OF INFLUENZA VIRUS HEMAGGLUTININ

    Shcherbinin, D.N.; S. V Alekseeva; Shmarov, M.M.; SMIRNOV YU.A.; Naroditskiy, B.S.; Gintsburg, A.L.

    2016-01-01

    Vaccination has been successfully used to prevent influenza for a long time. Influenza virus hemagglutinin (HA), which induces a humoral immune response in humans and protection against the flu, is the main antigenic component of modern influenza vaccines. However, new seasonal and pandemic influenza virus variants with altered structures of HA occasionally occur. This allows the pathogen to avoid neutralization with antibodies produced in response to previous vaccination. Development of a va...

  1. Experimental Evaluation of the FluChip Diagnostic Microarray for Influenza Virus Surveillance

    Townsend, Michael B.; Dawson, Erica D.; Mehlmann, Martin; Smagala, James A.; Dankbar, Daniela M.; Moore, Chad L.; Smith, Catherine B.; Cox, Nancy J.; Kuchta, Robert D.; Rowlen, Kathy L.

    2006-01-01

    Global surveillance of influenza is critical for improvements in disease management and is especially important for early detection, rapid intervention, and a possible reduction of the impact of an influenza pandemic. Enhanced surveillance requires rapid, robust, and inexpensive analytical techniques capable of providing a detailed analysis of influenza virus strains. Low-density oligonucleotide microarrays with highly multiplexed “signatures” for influenza viruses offer many of the desired c...

  2. Influenza and other respiratory viruses detected by influenza-like illness surveillance in Leyte Island, the Philippines, 2010-2013.

    Hirono Otomaru

    Full Text Available This study aimed to determine the role of influenza-like illness (ILI surveillance conducted on Leyte Island, the Philippines, including involvement of other respiratory viruses, from 2010 to 2013. ILI surveillance was conducted from January 2010 to March 2013 with 3 sentinel sites located in Tacloban city, Palo and Tanauan of Leyte Island. ILI was defined as fever ≥38°C or feverish feeling and either cough or running nose in a patient of any age. Influenza virus and other 5 respiratory viruses were searched. A total of 5,550 ILI cases visited the 3 sites and specimens were collected from 2,031 (36.6% cases. Among the cases sampled, 1,637 (75.6% were children aged <5 years. 874 (43.0% cases were positive for at least one of the respiratory viruses tested. Influenza virus and respiratory syncytial virus (RSV were predominantly detected (both were 25.7% followed by human rhinovirus (HRV (17.5%. The age distributions were significantly different between those who were positive for influenza, HRV, and RSV. ILI cases were reported throughout the year and influenza virus was co-detected with those viruses on approximately half of the weeks of study period (RSV in 60.5% and HRV 47.4%. In terms of clinical manifestations, only the rates of headache and sore throat were significantly higher in influenza positive cases than cases positive to other viruses. In conclusion, syndromic ILI surveillance in this area is difficult to detect the start of influenza epidemic without laboratory confirmation which requires huge resources. Age was an important factor that affected positive rates of influenza and other respiratory viruses. Involvement of older age children may be useful to detect influenza more effectively.

  3. Influenza virus neuraminidase (NA): a target for antivirals and vaccines.

    Jagadesh, Anitha; Salam, Abdul Ajees Abdul; Mudgal, Piya Paul; Arunkumar, Govindakarnavar

    2016-08-01

    Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage. PMID:27255748

  4. Tissue and host tropism of influenza viruses:Importance of quantitative analysis

    2009-01-01

    It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/ glycolipids containing sialic acids in α2,6-linkage; while avian and equine influenza viruses preferentially bind to those containing sialic acids in α2,3-linkage. Even though this generalized view is accurate for H3 subtype isolates, it may not be accurate and absolute for all subtypes of influenza A viruses and, therefore, needs to be reevaluated carefully and realistically. Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community. One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells. In addition, recent studies indicate that α2,3- and α2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses. In fact, determinants for tissue and host tropism of human, avian and animal influenza viruses are more complex than what has been generally accepted. Other factors, such as glycan topology, concentration of invading viruses, local density of receptors, lipid raft microdomains, coreceptors or sialic acid-independent receptors, may also be important. To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1, it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results. In this review, I will comment on some conflicting issues related to tissue and host tropism of influenza viruses, discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area, which should lead to a better

  5. Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China.

    Cui, Hongrui; Shi, Ying; Ruan, Tao; Li, Xuesong; Teng, Qiaoyang; Chen, Hongjun; Yang, Jianmei; Liu, Qinfang; Li, Zejun

    2016-01-01

    H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross-reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation, and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China. PMID:27270298

  6. Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China

    Cui, Hongrui; Shi, Ying; Ruan, Tao; Li, Xuesong; Teng, Qiaoyang; Chen, Hongjun; Yang, Jianmei; Liu, Qinfang; Li, Zejun

    2016-01-01

    H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross-reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation, and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China. PMID:27270298

  7. Cause of Flu (Influenza)

    ... Skip Content Marketing Share this: Main Content Area Flu (Influenza) Cause About the Flu Virus Influenza, or flu, is a respiratory infection ... the virus. Influenza A virus. Credit: CDC Where Influenza Comes From In nature, the flu virus is ...

  8. Quantifying homologous and heterologous antibody titre rises after influenza virus infection.

    Freeman, G; Perera, R A P M; Ngan, E; Fang, V J; Cauchemez, S; Ip, D K M; Peiris, J S M; Cowling, B J

    2016-08-01

    Most influenza virus infections are associated with mild disease. One approach to estimate the occurrence of influenza virus infections in individuals is via repeated measurement of humoral antibody titres. We used baseline and convalescent antibody titres measured by haemagglutination inhibition (HI) and viral neutralization (VN) assays against influenza A(H1N1), A(H3N2) and B viruses to investigate the characteristics of antibody rises following virologically confirmed influenza virus infections in participants in a community-based study. Multivariate models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following influenza A virus infections. In 122 participants with PCR-confirmed influenza A virus infection, homologous antibody titres rose by geometric means of 1·2- to 10·2-fold after infection with A(H1N1), A(H3N2) and A(H1N1)pdm09. Significant cross-reactions were observed between A(H1N1)pdm09 and seasonal A(H1N1). Antibody titre rises for some subtypes and assays varied by age, receipt of oseltamivir treatment, and recent receipt of influenza vaccination. In conclusion, we provided a quantitative description of the mean and variation in rises in influenza virus antibody titres following influenza virus infection. The multivariate patterns in boosting of antibody titres following influenza virus infection could be taken into account to improve estimates of cumulative incidence of infection in seroepidemiological studies. PMID:27018720

  9. Cyclophilin A protects mice against infection by influenza A virus.

    Li, Jing; Chen, Can; Wong, Gary; Dong, Wei; Zheng, Weinan; Li, Yun; Sun, Lei; Zhang, Lianfeng; Gao, George F; Bi, Yuhai; Liu, Wenjun

    2016-01-01

    Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections. PMID:27354005

  10. Cyclophilin A protects mice against infection by influenza A virus

    Li, Jing; Chen, Can; Wong, Gary; Dong, Wei; Zheng, Weinan; Li, Yun; Sun, Lei; Zhang, Lianfeng; Gao, George F.; Bi, Yuhai; Liu, Wenjun

    2016-01-01

    Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections. PMID:27354005

  11. Well-tolerated Spirulina extract inhibits influenza virus replication and reduces virus-induced mortality.

    Chen, Yi-Hsiang; Chang, Gi-Kung; Kuo, Shu-Ming; Huang, Sheng-Yu; Hu, I-Chen; Lo, Yu-Lun; Shih, Shin-Ru

    2016-01-01

    Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts and specific substances derived from Spirulina, and here we show that this Spirulina cold water extract has low cellular toxicity, and is well-tolerated in animal models at one dose as high as 5,000 mg/kg, or 3,000 mg/kg/day for 14 successive days. Anti-flu efficacy studies revealed that the Spirulina extract inhibited viral plaque formation in a broad range of influenza viruses, including oseltamivir-resistant strains. Spirulina extract was found to act at an early stage of infection to reduce virus yields in cells and improve survival in influenza-infected mice, with inhibition of influenza hemagglutination identified as one of the mechanisms involved. Together, these results suggest that the cold water extract of Spirulina might serve as a safe and effective therapeutic agent to manage influenza outbreaks, and further clinical investigation may be warranted. PMID:27067133

  12. Cross-protective immunity to influenza A viruses.

    Epstein, Suzanne L; Price, Graeme E

    2010-11-01

    Antigenic changes in influenza virus occur gradually, owing to mutations (antigenic drift), and abruptly, owing to reassortment among subtypes (antigenic shift). Availability of strain-matched vaccines often lags behind these changes, resulting in a shortfall in public health. In animal models, cross-protection by vaccines based on conserved antigens does not completely prevent infection, but greatly reduces morbidity, mortality, virus replication and, thus, viral shedding and spread. Such immunity is especially effective and long-lasting with mucosal administration. Cross-protective immunity in humans is controversial, but is suggested by some epidemiological findings. 'Universal' vaccines protective against all influenza A viruses might substantially reduce severity of infection and limit spread of disease during outbreaks. These vaccines could be used 'off the shelf' early in an outbreak or pandemic, before strain-matched vaccines are available. PMID:21087110

  13. Zoonosis Update on H9N2 Avian Influenza Virus

    Abdul Ahad*, Masood Rabbani, Altaf Mahmood1, Zulfiqar Hussan Kuthu2, Arfan Ahmad and Muhammad Mahmudur Rahman3

    2013-07-01

    Full Text Available Influenza A viruses infect various mammals like human, horse, pig and birds as well. A total of 16 hemagglutinin (HA and 9 neuraminidase (NA subtypes have been identified. Most of the combinations are found in birds and relatively few have been isolated from mammals. Although there is no report of human to human transmission till to date, several cases of H5N1, H7N7 and H9N2 identified in humans since 1997 raised serious concern for health and veterinary profession. This review paper will focus H9N2 avian influenza virus (AIV with special emphasis on zoonosis. The virus H9N2 though not highly pathogenic like H5N1 but can be virulent through antigenic drift and shift.

  14. European H16N3 gull influenza virus attaches to the human respiratory tract and eye.

    Cecilia Lindskog

    Full Text Available We explored the attachment of an H16N3 influenza virus to human, mallard, and gull tissues using virus histochemistry applied to tissue microarrays and employing human and mallard viruses as references. Of the viruses tested, the H16N3 gull virus most readily attached to the human respiratory tract and eye. These results underscore the need to assess the potential for gull influenza viruses to replicate in human tissues and further investigate the role of gulls in influenza virus ecology.

  15. Gnarled-trunk evolutionary model of influenza A virus hemagglutinin.

    Kimihito Ito

    Full Text Available Human influenza A viruses undergo antigenic changes with gradual accumulation of amino acid substitutions on the hemagglutinin (HA molecule. A strong antigenic mismatch between vaccine and epidemic strains often requires the replacement of influenza vaccines worldwide. To establish a practical model enabling us to predict the future direction of the influenza virus evolution, relative distances of amino acid sequences among past epidemic strains were analyzed by multidimensional scaling (MDS. We found that human influenza viruses have evolved along a gnarled evolutionary pathway with an approximately constant curvature in the MDS-constructed 3D space. The gnarled pathway indicated that evolution on the trunk favored multiple substitutions at the same amino acid positions on HA. The constant curvature was reasonably explained by assuming that the rate of amino acid substitutions varied from one position to another according to a gamma distribution. Furthermore, we utilized the estimated parameters of the gamma distribution to predict the amino acid substitutions on HA in subsequent years. Retrospective prediction tests for 12 years from 1997 to 2009 showed that 70% of actual amino acid substitutions were correctly predicted, and that 45% of predicted amino acid substitutions have been actually observed. Although it remains unsolved how to predict the exact timing of antigenic changes, the present results suggest that our model may have the potential to recognize emerging epidemic strains.

  16. 猪流感病毒的基因组结构及跨种属传播%The Genome Structure and Interspecies Transmission of Swine Influenza Virus

    刘业兵; 张磊; 张志刚

    2009-01-01

    猪是禽和哺乳动物流感病毒的中间宿主和产生重组病毒的混合器,猪流感病毒基因重排现象非常普遍.从猪流感病毒的形态结构、抗原性、基因组与主要编码蛋白、基因重排与跨种属传播等方面,对其研究情况进行了综述,以期为进一步了解猪流感病毒基因重排及种间传播机制,更好的防控流感疫情提供参考.%Swine is susceptible to both avian and mammalian influenza viruses and have been proposed to be intermediate hosts, and mixing vessels for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. The genetic recombination of swine influenza viruses is very prevalent. These aspects were described including of the morphological structure, antigenicity, genome structure and important proteins of swine influenza viruses, the genetic recombination and interspecies transmission, the research process of swine influenza viruses were summarized. The present study provides evidence for the research of the genetic recombination and interspecies transmission of swine influenza viruses, which help to prevent and control the influenza.

  17. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    Research highlights: → The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. → Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. → The universal antibodies cross-neutralize different influenza A subtypes. → The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  18. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    Hashem, Anwar M. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada); Van Domselaar, Gary [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Li, Changgui; Wang, Junzhi [National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China); She, Yi-Min; Cyr, Terry D. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Sui, Jianhua [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); He, Runtao [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Marasco, Wayne A. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada)

    2010-12-10

    Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  19. Cats as a potential source of emerging influenza virus infections

    Taisuke; Horimoto; Fumihiro; Gen; Shin; Murakami; Kiyoko; Iwatsuki-Horimoto; Kentaro; Kato; Masaharu; Hisasue; Masahiro; Sakaguchi; Chairul; A.; Nidom; Yoshihiro; Kawaoka

    2015-01-01

    <正>Dear Editor,Historically,the influenza virus has not been regarded as a major pathogen of cats.However,since 2003,natural infections of domestic cats with highly pathogenic H5N1 avian virus causing fatal cases have been reported(Songserm et al.,2006;Yingst et al.,2006;Klopfleisch et al.,2007).Furthermore,infections of this animal with A(H1N1)pdm09 virus,causing respiratory illness with some fatal cases,have also been reported in various parts

  20. Replication of avian influenza A viruses in mammals.

    Hinshaw, V S; Webster, R. G.; Easterday, B C; Bean, W J

    1981-01-01

    The recent appearance of an avian influenza A virus in seals suggests that viruses are transmitted from birds to mammals in nature. To examine this possibility, avian viruses of different antigenic subtypes were evaluated for their ability to replicate in three mammals-pigs, ferrets, and cats. In each of these mammals, avian strains replicated to high titers in the respiratory tract (10(5) to 10(7) 50% egg infective doses per ml of nasal wash), with peak titers at 2 to 4 days post-inoculation...

  1. Oligonucleotide microarray for subtyping of influenza A viruses

    Klotchenko, S. A.; Vasin, A. V.; Sandybaev, N. T.; Plotnikova, M. A.; Chervyakova, O. V.; Smirnova, E. A.; Kushnareva, E. V.; Strochkov, V. M.; Taylakova, E. T.; Egorov, V. V.; Koshemetov, J. K.; Kiselev, O. I.; Sansyzbay, A. R.

    2012-02-01

    Influenza is one of the most widespread respiratory viral diseases, infecting humans, horses, pigs, poultry and some other animal populations. Influenza A viruses (IAV) are classified into subtypes on the basis of the surface hemagglutinin (H1 to H16) and neuraminidase (N1 to N9) glycoproteins. The correct determination of IAV subtype is necessary for clinical and epidemiological studies. In this article we propose an oligonucleotide microarray for subtyping of IAV using universal one-step multisegment RT-PCR fluorescent labeling of viral gene segments. It showed to be an advanced approach for fast detection and identification of IAV.

  2. Oligonucleotide microarray for subtyping of influenza A viruses

    Influenza is one of the most widespread respiratory viral diseases, infecting humans, horses, pigs, poultry and some other animal populations. Influenza A viruses (IAV) are classified into subtypes on the basis of the surface hemagglutinin (H1 to H16) and neuraminidase (N1 to N9) glycoproteins. The correct determination of IAV subtype is necessary for clinical and epidemiological studies. In this article we propose an oligonucleotide microarray for subtyping of IAV using universal one-step multisegment RT-PCR fluorescent labeling of viral gene segments. It showed to be an advanced approach for fast detection and identification of IAV.

  3. Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

    Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine

    2016-01-01

    Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and ...

  4. Low pathogenic avian influenza isolates from wild birds replicate and transmit via contact in ferrets without prior adaptation.

    Elizabeth A Driskell

    Full Text Available Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA residues with α 2,3 linkage [Neu5Ac(α2,3Gal]. Despite the lack of α2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for α 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential.

  5. In ovo and in vitro susceptibility of American alligators (Alligator mississippiensis) to avian influenza virus infection.

    Temple, Bradley L; Finger, John W; Jones, Cheryl A; Gabbard, Jon D; Jelesijevic, Tomislav; Uhl, Elizabeth W; Hogan, Robert J; Glenn, Travis C; Tompkins, S Mark

    2015-01-01

    Avian influenza has emerged as one of the most ubiquitous viruses within our biosphere. Wild aquatic birds are believed to be the primary reservoir of all influenza viruses; however, the spillover of H5N1 highly pathogenic avian influenza (HPAI) and the recent swine-origin pandemic H1N1 viruses have sparked increased interest in identifying and understanding which and how many species can be infected. Moreover, novel influenza virus sequences were recently isolated from New World bats. Crocodilians have a slow rate of molecular evolution and are the sister group to birds; thus they are a logical reptilian group to explore susceptibility to influenza virus infection and they provide a link between birds and mammals. A primary American alligator (Alligator mississippiensis) cell line, and embryos, were infected with four, low pathogenic avian influenza (LPAI) strains to assess susceptibility to infection. Embryonated alligator eggs supported virus replication, as evidenced by the influenza virus M gene and infectious virus detected in allantoic fluid and by virus antigen staining in embryo tissues. Primary alligator cells were also inoculated with the LPAI viruses and showed susceptibility based upon antigen staining; however, the requirement for trypsin to support replication in cell culture limited replication. To assess influenza virus replication in culture, primary alligator cells were inoculated with H1N1 human influenza or H5N1 HPAI viruses that replicate independent of trypsin. Both viruses replicated efficiently in culture, even at the 30 C temperature preferred by the alligator cells. This research demonstrates the ability of wild-type influenza viruses to infect and replicate within two crocodilian substrates and suggests the need for further research to assess crocodilians as a species potentially susceptible to influenza virus infection. PMID:25380354

  6. Optimisations and Challenges Involved in the Creation of Various Bioluminescent and Fluorescent Influenza A Virus Strains for In Vitro and In Vivo Applications.

    Monique I Spronken

    Full Text Available Bioluminescent and fluorescent influenza A viruses offer new opportunities to study influenza virus replication, tropism and pathogenesis. To date, several influenza A reporter viruses have been described. These strategies typically focused on a single reporter gene (either bioluminescent or fluorescent in a single virus backbone. However, whilst bioluminescence is suited to in vivo imaging, fluorescent viruses are more appropriate for microscopy. Therefore, the idea l reporter virus varies depending on the experiment in question, and it is important that any reporter virus strategy can be adapted accordingly. Herein, a strategy was developed to create five different reporter viruses in a single virus backbone. Specifically, enhanced green fluorescent protein (eGFP, far-red fluorescent protein (fRFP, near-infrared fluorescent protein (iRFP, Gaussia luciferase (gLUC and firefly luciferase (fLUC were inserted into the PA gene segment of A/PR/8/34 (H1N1. This study provides a comprehensive characterisation of the effects of different reporter genes on influenza virus replication and reporter activity. In vivo reporter gene expression, in lung tissues, was only detected for eGFP, fRFP and gLUC expressing viruses. In vitro, the eGFP-expressing virus displayed the best reporter stability and could be used for correlative light electron microscopy (CLEM. This strategy was then used to create eGFP-expressing viruses consisting entirely of pandemic H1N1, highly pathogenic avian influenza (HPAI H5N1 and H7N9. The HPAI H5N1 eGFP-expressing virus infected mice and reporter gene expression was detected, in lung tissues, in vivo. Thus, this study provides new tools and insights for the creation of bioluminescent and fluorescent influenza A reporter viruses.

  7. Neuraminidase and hemagglutinin matching patterns of a highly pathogenic avian and two pandemic H1N1 influenza A viruses.

    Yonghui Zhang

    Full Text Available BACKGROUND: Influenza A virus displays strong reassortment characteristics, which enable it to achieve adaptation in human infection. Surveying the reassortment and virulence of novel viruses is important in the prevention and control of an influenza pandemic. Meanwhile, studying the mechanism of reassortment may accelerate the development of anti-influenza strategies. METHODOLOGY/PRINCIPAL FINDINGS: The hemagglutinin (HA and neuraminidase (NA matching patterns of two pandemic H1N1 viruses (the 1918 and current 2009 strains and a highly pathogenic avian influenza A virus (H5N1 were studied using a pseudotyped particle (pp system. Our data showed that four of the six chimeric HA/NA combinations could produce infectious pps, and that some of the chimeric pps had greater infectivity than did their ancestors, raising the possibility of reassortment among these viruses. The NA of H5N1 (A/Anhui/1/2005 could hardly reassort with the HAs of the two H1N1 viruses. Many biological characteristics of HA and NA, including infectivity, hemagglutinating ability, and NA activity, are dependent on their matching pattern. CONCLUSIONS/SIGNIFICANCE: Our data suggest the existence of an interaction between HA and NA, and the HA NA matching pattern is critical for valid viral reassortment.

  8. Rapid semiautomated subtyping of influenza virus species during the 2009 swine origin influenza A H1N1 virus epidemic in Milwaukee, Wisconsin.

    Bose, Michael E; Beck, Eric T; Ledeboer, Nate; Kehl, Sue C; Jurgens, Lisa A; Patitucci, Teresa; Witt, Lorraine; LaGue, Elizabeth; Darga, Patrick; He, Jie; Fan, Jiang; Kumar, Swati; Henrickson, Kelly J

    2009-09-01

    In the spring of 2009, a novel influenza A (H1N1) virus (swine origin influenza virus [S-OIV]) emerged and began causing a large outbreak of illness in Milwaukee, WI. Our group at the Midwest Respiratory Virus Program laboratory developed a semiautomated real-time multiplex reverse transcription-PCR assay (Seasonal), employing the NucliSENS easyMAG system (bioMérieux, Durham, NC) and a Raider thermocycler (HandyLab Inc., Ann Arbor, MI), that typed influenza A virus, influenza B virus, and respiratory syncytial virus (RSV) and subtyped influenza A virus into the currently circulating H1 and H3 subtypes, as well as a similar assay that identified H1 of S-OIV. The Seasonal and H1 S-OIV assays demonstrated analytical limits of detection of tissue culture infective doses/ml and 3 to 30 input copies, respectively. Testing of the analytical specificities revealed no cross-reactivity with 41 and 26 different common organisms and demonstrated outstanding reproducibility of results. Clinical testing showed 95% sensitivity for influenza A virus and influenza B virus and 95 and 97% specificity compared to tissue culture. Comparisons of results from other molecular tests showed levels of positive agreement with the Seasonal and H1 S-OIV assay results of 99 and 100% and levels of negative agreement of 98 and 100%. This study has demonstrated the use of a semiautomated system for sensitive, specific, and rapid detection of influenza A virus, influenza B virus, and RSV and subtyping of influenza A virus into human H1 and H3 and S-OIV strains. This assay/system performed well in clinical testing of regular seasonal influenza virus subtypes and was outstanding during the 2009 Milwaukee S-OIV infection outbreak. This recent outbreak of infection with a novel influenza A (H1N1) virus also demonstrates the importance of quickly distributing information on new agents and of having rapid influenza virus subtyping assays widely available for clinical and public health decisions. PMID

  9. Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013

    J. Watson, Simon; Langat, Pinky; M. Reid, Scott;

    2015-01-01

    The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data...

  10. Novel Avian Influenza A(H7N9) Virus in Tree Sparrow, Shanghai, China, 2013

    Zhao, Baihui; Zhang, Xi; Zhu, Wenfei; Teng, Zheng; Yu, Xuelian; Gao, Ye; Wu, Di; Pei, Enle; Yuan, Zhengan; Lei YANG; Wang, Dayan; Shu, Yuelong; Wu, Fan

    2014-01-01

    In spring 2013, influenza A(H7N9) virus was isolated from an apparently healthy tree sparrow in Chongming Dongping National Forest Park, Shanghai City, China. The entire gene constellation of the virus is similar to that of isolates from humans, highlighting the need to monitor influenza A(H7N9) viruses in different species.

  11. Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies

    Fukuyama, Satoshi; Katsura, Hiroaki; Zhao, Dongming; Ozawa, Makoto; Ando, Tomomi; Shoemaker, Jason E.; Ishikawa, Izumi; Yamada, Shinya; Neumann, Gabriele; Watanabe, Shinji; Kitano, Hiroaki; Kawaoka, Yoshihiro

    2015-01-01

    Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours (‘Color-flu’ viruses) to facilitate the study of viral infection in...

  12. Construction of the influenza A virus transmission tree in a college-based population: co-transmission and interactions between influenza A viruses

    Zhang, Xu-Sheng; De Angelis, Daniela

    2016-01-01

    Background Co-infection of different influenza A viruses is known to occur but how viruses interact within co-infection remains unknown. An outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza A: persons infected with pandemic A/H1N1; persons infected with seasonal A/H3N2 viruses; and persons infected with both at the same time (co-infection). This provides data to analyse the possible interaction between influenza A viruses within co-infection. Methods We ...

  13. Reconstruction of H3N2 influenza virus based virosome in-vitro

    Mohammad Hesam Sohani; Abbas jamali; Masoumeh Tavassoti Kheiri; Hoorieh Soleimanjahi; Asghar Abdoli; Mohsen Abdoli; Hamidreza Rahmatollahi

    2013-01-01

    Background and Objectives: Virosomes are Virus Like Particles (VLP) assembled in-vitro. Influenza virosomes maintain the cell binding and membrane fusion activity of the wild type virus but are devoid of viral genetic material or internal proteins. Influenza virosomes mimic the natural antigen presentation route of the influenza virus.Methods: Virosomes were prepared by membrane solubilization and reconstitution. Briefly, the Madine-Darby Canine kidney (MDCK) cell line was cultivated on micro...

  14. Targeting Organic Anion Transporter 3 with Probenecid as a Novel Anti-Influenza A Virus Strategy

    Perwitasari, Olivia; Yan, Xiuzhen; Johnson, Scott; White, Caleb; Brooks, Paula; Tompkins, S. Mark; Tripp, Ralph A.

    2013-01-01

    Influenza A virus infection is a major global health concern causing significant mortality, morbidity, and economic loss. Antiviral chemotherapeutics that target influenza A virus are available; however, rapid emergence of drug-resistant strains has been reported. Consequently, there is a burgeoning need to identify novel anti-influenza A drugs, particularly those that target host gene products required for virus replication, to reduce the likelihood of drug resistance. In this study, a small...

  15. Inhibition of Influenza A Virus Infection In Vitro by Peptides Designed In Silico

    Rogelio López-Martínez; G Lizbeth Ramírez-Salinas; José Correa-Basurto; Barrón, Blanca L.

    2013-01-01

    Influenza A viruses are enveloped, segmented negative single-stranded RNA viruses, capable of causing severe human respiratory infections. Currently, only two types of drugs are used to treat influenza A infections, the M2 H(+) ion channel blockers (amantadine and rimantadine) and the neuraminidase inhibitors (NAI) (oseltamivir and zanamivir). Moreover, the emergence of drug-resistant influenza A virus strains has emphasized the need to develop new antiviral agents to complement or replace th...

  16. Avian Influenza A Virus in Wild Birds in Highly Urbanized Areas

    2012-01-01

    Avian influenza virus (AIV) surveillance studies in wild birds are usually conducted in rural areas and nature reserves. Less is known of avian influenza virus prevalence in wild birds located in densely populated urban areas, while these birds are more likely to be in close contact with humans. Influenza virus prevalence was investigated in 6059 wild birds sampled in cities in the Netherlands between 2006 and 2009, and compared with parallel AIV surveillance data from low urbanized areas in ...

  17. Surveillance of avian influenza viruses in Papua New Guinean poultry, June 2011 to April 2012

    Marinjho Jonduo; Sook-San Wong; Nime Kapo; Paskalis Ominipi; Mohammad Abdad; Peter Siba; Pamela McKenzie; Richard Webby; Paul Horwood

    2013-01-01

    We investigated the circulation of avian influenza viruses in poultry populations throughout Papua New Guinea to assess the risk to the poultry industry and human health. Oropharyngeal swabs, cloacal swabs and serum were collected from 537 poultry from 14 provinces of Papua New Guinea over an 11–month period (June 2011 through April 2012). Virological and serological investigations were undertaken to determine the prevalence of avian influenza viruses. Neither influenza A viruses nor antibodi...

  18. Homologous interference mediated by defective interfering influenza virus derived from a temperature-sensitive mutant of influenza virus

    A temperature-sensitive group II mutant of influenza virus, ts-52, with a presumed defect in viral RNA synthesis, readily produced von Magnus-type defective interfering virus (DI virus) when passed serially (four times) at high multiplicity in MDBK cells. The defective virus (ts-52 DI virus) had a high hemagglutinin and a low infectivity titer, and strongly interfered with the replication of standard infectious viruses (both ts-52 and wild-type ts+) in co-infected cells. Progeny virus particles produced by co-infection of DI virus and infectious virus were also defective and also had low infectivity, high hemagglutinating activity, and a strong interfering property. Infectious viruses ts+ and ts-52 were indistinguishable from ts-52 DI viruses by sucrose velocity or density gradient analysis. Additionally, these viruses all possessed similar morphology. However, when the RNA of DI viruses was analyzed by use of polyacrylamide gels containing 6 M urea, there was a reduction in the amount of large RNA species (V1 to V4), and a number of new smaller RNA species (D1 to D6) with molecular weights ranging from 2.9 x 105 to 1.05 x 105 appeared. Since these smaller RNA species (D1 to D6) were absent in some clones of infectious viruses, but were consistently associated with DI viruses and increased during undiluted passages and during co-infection of ts-52 with DI virus, they appeared to be a characteristic of DI viruses. Additionally, the uv target size of interfering activity and infectivity of DI virus indicated that interfering activity was 40 times more resistant to uv irradiation than was infectivity, further implicating small RNA molecules in interference

  19. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know?

    Minodier, Laetitia; Charrel, Remi N.; Ceccaldi, Pierre-Emmanuel; van der Werf, Sylvie; Blanchon, Thierry; Hanslik, Thomas; Falchi, Alessandra

    2015-01-01

    This review provides for the first time an assessment of the current understanding about the occurrence and the clinical significance of gastrointestinal (GI) symptoms in influenza patients, and their correlation with the presence of human influenza viruses in stools of patients with confirmed influenza virus infection. Studies exploring how human influenza viruses spread to the patient’s GI tract after a primary respiratory infection have been summarized. We conducted a systematic search of ...

  20. Reduced incorporation of the influenza B virus BM2 protein in virus particles decreases infectivity

    BM2 is the fourth integral membrane protein encoded by the influenza B virus genome. It is synthesized late in infection and transported to the plasma membrane from where it is subsequently incorporated into progeny virus particles. It has recently been reported that BM2 has ion channel activity and may be the functional homologue of the influenza A virus M2 protein acting as an ion channel involved in viral entry. Using a reverse genetic approach it was not possible to recover virus which lacked BM2. A recombinant influenza B virus was generated in which the BM2 AUG initiation codon was mutated to GUG. This decreased the efficiency of translation of BM2 protein such that progeny virions contained only 1/8 the amount of BM2 seen in wild-type virus. The reduction in BM2 incorporation resulted in a reduction in infectivity although there was no concomitant decrease in the numbers of virions released from the infected cells. These data imply that the incorporation of sufficient BM2 protein into influenza B virions is required for infectivity of the virus particles

  1. Transmission of Avian Influenza Virus (H3N2) to Dogs

    Song, Daesub; Kang, Bokyu; Lee, Chulseung; Jung, Kwonil; Ha, Gunwoo; Kang, Dongseok; Park, Seongjun; Park, Bongkyun; Oh, Jinsik

    2008-01-01

    In South Korea, where avian influenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine influenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. To determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (H3N2) is...

  2. Influenza virus assays based on virus‐inducible reporter cell lines

    Li, Yunsheng; Larrimer, Audrey; Curtiss, Teresa; Kim, Jaekyung; Jones, Abby; Baird‐Tomlinson, Heather; Pekosz, Andrew; Olivo, Paul D.

    2009-01-01

    Background  Virus‐inducible reporter genes have been used as the basis of virus detection and quantitation assays for a number of viruses. A strategy for influenza A virus‐induction of a reporter gene was recently described. In this report, we describe the extension of this strategy to influenza B virus, the generation of stable cell lines with influenza A and B virus‐inducible reporter genes, and the use of these cells in various clinically relevant viral assays. Each of the cell lines described herein constitutively express an RNA transcript that contains a reporter gene coding region flanked by viral 5′‐ and 3′‐untranslated regions (UTR) and therefore mimics an influenza virus genomic segment. Upon infection of the cells with influenza virus the virus‐inducible reporter gene segment (VIRGS) is replicated and transcribed by the viral polymerase complex resulting in reporter gene expression. Findings  Reporter gene induction occurs after infection with a number of laboratory strains and clinical isolates of influenza virus including several H5N1 strains. The induction is dose‐dependent and highly specific for influenza A or influenza B viruses. Conclusions  These cell lines provide the basis of simple, rapid, and objective assays that involve virus quantitation such as determination of viral titer, assessment of antiviral susceptibility, and determination of antibody neutralization titer. These cell lines could be very useful for influenza virus researchers and vaccine manufacturers. PMID:21462401

  3. Swine-origin influenza-virus-induced acute lung injury:Novel or classical pathogenesis?

    Naoyoshi; Maeda; Toshimitsu; Uede

    2010-01-01

    Influenza viruses are common respiratory pathogens in humans and can cause serious infection that leads to the development of pneumonia.Due to their hostrange diversity,genetic and antigenic diversity,and potential to reassort genetically in vivo,influenza A viruses are continual sources of novel influenza strains that lead to the emergence of periodic epidemics and outbreaks in humans.Thus,newly emerging viral diseases are always major threats to public health.In March 2009,a novel influenza virus suddenly emerged and caused a worldwide pandemic.The novel pandemic influenza virus was genetically and antigenically distinct from previous seasonal human influenza A/H1N1 viruses;it was identified to have originated from pigs,and further genetic analysis revealed it as a subtype of A/H1N1,thus later called a swine-origin influenza virus A/H1N1.Since the novel virus emerged,epidemiological surveys and research on experimental animal models have been conducted,and characteristics of the novel influenza virus have been determined but the exact mechanisms of pulmonary pathogenesis remain to be elucidated.In this editorial,we summa-rize and discuss the recent pandemic caused by the novel swine-origin influenza virus A/H1N1 with a focus on the mechanism of pathogenesis to obtain an insight into potential therapeutic strategies.

  4. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

    Tate, M.D.; Pickett, D L; Rooijen, van, J.; Brooks, A G; Reading, P C

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus str...

  5. In Vitro Antiviral Effect of "Nanosilver" on Influenza Virus

    P Mehrbod

    2009-08-01

    Full Text Available Introduction: Influenza is a viral infectious disease with frequent seasonal epidemics causing world-wide economical and social effects. Due to antigenic shifts and drifts of influenza virus, long-lasting vaccine has not been developed so far. The current annual vaccines and effective antiviral drugs are not available sufficiently. Therefore in order to prevent spread of infectious agents including viruses, antiseptics are considered by world health authorities. Small particles of silver have a long history as general antiseptic and disinfectant. Silver does not induce resistance in microorganisms and this ability in Nano-size is stronger. Materials and methods: The aim of this study was to determine antiviral effects of Nanosilver against influenza virus. TCID50 (50% Tissue Culture Infectious Dose of the virus as well as CC50 (50% Cytotoxic Concentration of Nanosilver was obtained by MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide, Sigma method. This compound was non-toxic to MDCK (Madin-Darbey Canin Kidney cells at concentration up to 1 µg/ml.  Effective minimal cytotoxic concentration and 100 TCID50 of the virus were added to the confluent cells.  Inhibitory effects of Nanosilver on the virus and its cytotoxicity were assessed at different temperatures using Hemagglutination (HA assay, RT-PCR (Reverse Transcriptase-Polymerase Chain Reaction, and DIF (Direct Immunofluorescent. RT-PCR and free band densitometry software were used to compare the volume of the PCR product bands on the gel. Results and Discussion:  In this study it was found that Nanosilver has destructive effect on the virus membrane glycoprotein knobs as well as the cells.

  6. Detection of influenza A virus RNA in birds by optimized Real-Time PCR system

    Ilinykh Ph A; Shestopalova EM; Khripko Yu I; Durimanov AG; Sharshov KA; Shestopalov AM

    2010-01-01

    Objective: To evaluate the use of Real-Time PCR system based on specific amplification of matrix protein gene fragment for influenza A virus RNA detection in cloacal swabs from wild birds. Methods:Sensitivity, specificity and reproducibility of analysis results were identified. Study of cloacal swabs from wild birds for influenza A virus presence was performed. Results:Reproducibility of low concentrations of virus detection in samples by Real-Time PCR was significantly higher than that of detection based on cytopathic effect of viruses grown on MDCK cell culture. Conclusions: Real-Time PCR system for influenza A virus RNA detection is developed and applied for virus surveillance study.

  7. Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

    Roberts Paul C

    2009-04-01

    Full Text Available Abstract Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1, demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC. Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4 fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.

  8. Dogs are highly susceptible to H5N1 avian influenza virus

    Chen, Ying; Zhong, Gongxun; Wang, Guojun; Deng, Guohua; Li, Yanbing; Shi, Jianzhong; Zhang, Zhuo; Guan, Yuntao; Jiang, Yongping; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2010-01-01

    Replication of avian influenza viruses (AIVs) in dogs may facilitate their adaptation in humans; however, the data to date on H5N1 influenza virus infection in dogs are conflicting. To elucidate the susceptibility of dogs to this pathogen, we infected two groups of 6 beagles with 106 50% egg-infectious dose of H5N1 AIV A/bar-headed goose/Qinghai/3/05 (BHG/QH/3/05) intranasally (i.n.) and intratracheally (i.t.), respectively. The dogs showed disease symptoms, including anorexic, fever, conjunctivitis, labored breathing and cough, and one i.t. inoculated animal died on day 4 post-infection. Virus shedding was detected from all 6 animals inoculated i.n. and one inoculated i.t. Virus replication was detected in all animals that were euthanized on day 3 or 5 post-infection and in the animal that died on day 4 post-infection. Our results demonstrate that dogs are highly susceptible to H5N1 AIV and may serve as an intermediate host to transfer this virus to humans. PMID:20580396

  9. Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

    Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine

    2016-01-01

    Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed. PMID:26973644

  10. A novel reassortant canine H3N1 influenza virus between pandemic H1N1 and canine H3N2 influenza viruses in Korea

    Song, Daesub; Moon, Hyoung-Joon; An, Dong-Jun; Jeoung, Hye-Young; Kim, Hyekwon; Yeom, Min-Joo; Hong, Minki; Nam, Jeong-Hyun; Park, Seong-Jun; Park, Bong-Kyun; Oh, Jin-Sik; Song, Manki; Webster, Robert G; Kim, Jeong-Ki; Kang, Bo-Kyu

    2012-01-01

    During recent canine influenza surveillance in South Korea, a novel H3N1 canine influenza virus (CIV) that is a putative reassortant between pandemic H1N1 2009 and H3N2 CIVs was isolated. Genetic analysis of eight genes of the influenza virus revealed that the novel H3N1 isolate presented high similarities (99.1–99.9 %) to pandemic influenza H1N1, except for in the haemagglutinin (HA) gene. The HA gene nucleotide sequence of the novel CIV H3N1 was similar (99.6 %) to that of CIV H3N2 isolated...

  11. Antibody-Dependent Cell-Mediated Cytotoxicity to Hemagglutinin of Influenza A Viruses After Influenza Vaccination in Humans

    Zhong, Weimin; Liu, Feng; Wilson, Jason R.; Holiday, Crystal; Li, Zhu-Nan; Bai, Yaohui; Tzeng, Wen-Pin; Stevens, James; York, Ian A.; Levine, Min Z.

    2016-01-01

    Background. Detection of neutralizing antibodies (nAbs) to influenza A virus hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However, current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred. Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection. Methods. Virus neutralization and ADCC activities of serum samples from individuals who received either seasonal or a stock-piled H5N1 avian influenza vaccine were evaluated by hemagglutination inhibition assay, microneutralization assay, and an improved ADCC natural killer (NK) cell activation assay. Results. Immunization with inactivated seasonal influenza vaccine led to strong expansion of both nAbs and ADCC-mediating antibodies (adccAbs) to H3 antigen of the vaccine virus in 24 postvaccination human sera. In sharp contrast, 18 individuals vaccinated with the adjuvanted H5N1 avian influenza vaccine mounted H5-specific antibodies with strong ADCC activities despite moderate virus neutralization capacity. Strength of HA-specific ADCC activities is largely associated with the titers of HA-binding antibodies and not with the fine antigenic specificity of anti-HA nAbs. Conclusions. Detection of both nAbs and adccAbs may better reflect protective capacity of HA-specific antibodies induced by avian influenza vaccines.

  12. Nationwide molecular surveillance of pandemic H1N1 influenza A virus genomes: Canada, 2009.

    Morag Graham

    Full Text Available BACKGROUND: In April 2009, a novel triple-reassortant swine influenza A H1N1 virus ("A/H1N1pdm"; also known as SOIV was detected and spread globally as the first influenza pandemic of the 21(st century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior. METHODOLOGY/PRINCIPAL FINDINGS: By Sanger sequencing, we determined consensus whole-genome sequences for A/H1N1pdm viruses sampled nationwide in Canada over 33 weeks during the 2009 first and second pandemic waves. A total of 235 virus genomes sampled from unique subjects were analyzed, providing insight into the temporal and spatial trajectory of A/H1N1pdm lineages within Canada. Three clades (2, 3, and 7 were identifiable within the first two weeks of A/H1N1pdm appearance, with clades 5 and 6 appearing thereafter; further diversification was not apparent. Only two viral sites displayed evidence of adaptive evolution, located in hemagglutinin (HA corresponding to D222 in the HA receptor-binding site, and to E374 at HA2-subunit position 47. Among the Canadian sampled viruses, we observed notable genetic diversity (1.47 x 10⁻³ amino acid substitutions per site in the gene encoding PB1, particularly within the viral genomic RNA (vRNA-binding domain (residues 493-757. This genome data set supports the conclusion that A/H1N1pdm is evolving but not excessively relative to other H1N1 influenza A viruses. Entropy analysis was used to investigate whether any mutated A/H1N1pdm protein residues were associated with infection severity; however no virus genotypes were observed to trend with infection severity. One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown. CONCLUSIONS/SIGNIFICANCE: These findings contribute to

  13. Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia

    I.A. Leneva

    2016-02-01

    Conclusions: This study provided experimental and clinical evidence of the efficacy of oseltamivir and umifenovir against influenza viruses, representatives of which have continued to circulate in post-pandemic seasons.

  14. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells

    Psoralen compounds covalently bind to nucleic acids when irradiated with long-wavelength ultraviolet light. This treatment can destroy the infectivity of deoxyribonucleic acid and ribonucleic acid viruses. Two psoralen compounds, 4'-hydroxymethyltrioxsalen and 4'-aminomethyltrioxsalen, were used with long-wavelength ultraviolet light to inactivate cell-free herpes simplex and influenza viruses and to render virus-infected cells noninfectious. This method of inactivation was compared with germicidal (short-wavelength) ultraviolet light irradiation. The antigenicity of the treated, virus-infected, antigen-bearing cells was examined by immunofluorescence and radioimmunoassay and by measuring the capacity of the herpes simplex virus-infected cells to stimulate virus-specific lymphocyte proliferation. The infectivity of the virus-infected cells could be totally eliminated without altering their viral antigenicity. The use of psoralen plus long-wavelength ultraviolet light is well suited to the preparation of noninfectious virus antigens and virus antigen-bearing cells for immunological assays

  15. Influenza and respiratory syncytial viruses: Efficacy of different diagnostic assays

    Rahman, M.M.; K K Wong; Alfizah, H.; Hussin, S.; Isahak, I.

    2015-01-01

    Objective: To determine the efficacy of cell culture, immunoflourescence Assay (IFA) and real time polymerase chain reaction (rRT-PCR) in relation to diagnosis of influenza and Respiratory Syncytial Virus (RSV). Methods: Total 2781 specimens of throat swabs and nasopharyngeal aspirates were obtained from patients suspected of respiratory viruses’ infections from January 2009 to December 2011 at Universiti Kebangsaan Malaysia Medical Centre(UKMMC). The specimens were processed by cell culture ...

  16. Polyphylla saponin I has antiviral activity against influenza A virus

    Pu, XiuYing; Ren, Jing; Ma, Xiaolong; Liu, Lu; Yu, Shuang; Li, Xiaoyue; Li, Haibing

    2015-01-01

    Objective: In the present study, the antiviral effects of polyphylla saponin I isolated from Parispolyphylla on influenza A virus are investigated both in vitro and in vivo. Methods: Column chromatography and reversed phase liquid chromatography separation technology were used to extract and purify polyphylla saponin I. The purity of polyphylla saponin I was assayed by high performance liquid chromatography. Methyl thiazolyl tetrazolium assay and analyses of cytopathic effects were performed ...

  17. Potential of acylated peptides to target the influenza A virus

    Daniel Lauster

    2015-04-01

    Full Text Available For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral Peptide B (PeBGF, preventing binding of influenza virus to the host cell. By conjugating the peptide with stearic acid to create a higher-order structure with a multivalent display, we could significantly enhance the inhibitory effect against the serotypes of both human pathogenic influenza virus A/Aichi/2/1968 H3N2, and avian pathogenic A/FPV/Rostock/34 H7N1 in the hemagglutination inhibition assay. Further, the inhibitory potential of stearylated PeBGF (C18-PeBGF was investigated by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010, and the “Entry Blocker” (EB (Jones et al. 2006, with respect to their antiviral activity against infection by Influenza A Virus (IAV H3N2. However, while this strategy seems at a first glance promising, the native situation is quite different from our experimental model settings. First, we found a strong potential of those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious limitations of this type of self-assembling IAV inhibitors.

  18. Novel genetic reassortants in H9N2 influenza A viruses and their diverse pathogenicity to mice

    Bi Yuhai

    2011-11-01

    Full Text Available Abstract Background H9N2 influenza A viruses have undergone extensive reassortments in different host species, and could lead to the epidemics or pandemics with the potential emergence of novel viruses. Methods To understand the genetic and pathogenic features of early and current circulating H9N2 viruses, 15 representative H9N2 viruses isolated from diseased chickens in northern China between 1998 and 2010 were characterized and compared with all Chinese H9N2 viruses available in the NCBI database. Then, the representative viruses of different genotypes were selected to study the pathogenicity in mice with the aim to investigate the adaptation and the potential pathogenicity of the novel H9N2 reassortants to mammals. Results Our results demonstrated that most of the 15 isolates were reassortants and generated four novel genotypes (B62-B65, which incorporated the gene segments from Eurasian H9N2 lineage, North American H9N2 branch, and H5N1 viruses. It was noteworthy that the newly identified genotype B65 has been prevalent in China since 2007, and more importantly, different H9N2 influenza viruses displayed a diverse pathogenicity to mice. The isolates of the 2008-2010 epidemic (genotypes B55 and B65 were lowly infectious, while two representative viruses of genotypes B0 and G2 isolated from the late 1990s were highly pathogenic to mice. In addition, Ck/SD/LY-1/08 (genotype 63, containing H5N1-like NP and PA genes was able to replicate well in mouse lungs with high virus titers but caused mild clinical signs. Conclusion Several lines of evidence indicated that the H9N2 influenza viruses constantly change their genetics and pathogenicity. Thus, the genetic evolution of H9N2 viruses and their pathogenicity to mammals should be closely monitored to prevent the emergence of novel pandemic viruses.

  19. Pandemic H1N1 influenza virus infection in a Canadian cat.

    Knight, Cameron G; Davies, Jennifer L; Joseph, Tomy; Ondrich, Sarah; Rosa, Brielle V

    2016-05-01

    A cat was presented for necropsy after being found dead at home. Histologic findings suggested viral pneumonia. Polymerase chain reaction and viral typing revealed influenza A(H1N1)pdm09. This is the first report of influenza in a Canadian cat and highlights the importance of considering influenza virus in the differential diagnosis for feline respiratory distress. PMID:27152036

  20. Human Infection from Avian-like Influenza A (H1N1) Viruses in Pigs, China

    Yang, Huanliang; Qiao, Chuanling; Tang, Xu; Chen, Yan; Xin, Xiaoguang; Chen, Hualan

    2012-01-01

    In investigating influenza in an immunodeficient child in China, in December 2010, we found that the influenza virus showed high sequence identity to that of swine. Serologic evidence indicated that viral persistence in pigs was the source of infection. Continued surveillance of pigs and systemic analysis of swine influenza isolates are needed.

  1. Mechanism of aftered cytoskeleton organization in influenza virus infection

    The autophosphorylation was followed of cytoskeleton (CS) isolated from control chick embryo cell membranes (CS-C) and from these membranes after influenza virus adsorption (CS-V) under conditions allowing to determine the activity of a single type proteinkinase. The Ca2+ dependent calmodulin (CaM) kinase used different substrates from CS-V than did the c'AMP dependent proteinkinase. The catalytic subunit (c-subunit) of the c'AMP dependent proteinkinase added from outside phosphorylated the same polypeptides than the endogeneous c'AMP dependent proteinkinase, the further being more active than the latter. The purified influenza virus incorporated 32P in the presence of the c-subunit only. Incubation of influenza virus with the c-subunit caused morphological changes visible by electron microscopy. The pleomorphy of the particles as well as their electron transmissibility were enhanced in the result of structural alterations and rarefaction of surface spikes of the haemagglutinin and neuraminidase. The contractibility of CS isolated from normal CEC and of the CS from CEC by 15 min postinfection (p.i.) was determined according to the actomyosin ATPase activity. The ATPase activity of the cytoskeleton in the presence of the Ca2+/CaM and that in the presence of c'AMP were used as controls. The virus as well as the Ca2+/CaM increased the ATPase activity. EGTA had no effect but did not interfere with virus stimulation, while c'AMP blocked the virus-induced enhancement of the ATPase activity. (author). 3 figs., 1 tab., 36 refs

  2. Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment

    Kristin A. Gabor

    2014-11-01

    Full Text Available Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in substantial morbidity, mortality and economic burdens. Prevention and treatment of influenza illness is difficult due to the high mutation rate of the virus, the emergence of new virus strains and increasing antiviral resistance. Animal models of influenza infection are crucial to our gaining a better understanding of the pathogenesis of and host response to influenza infection, and for screening antiviral compounds. However, the current animal models used for influenza research are not amenable to visualization of host-pathogen interactions or high-throughput drug screening. The zebrafish is widely recognized as a valuable model system for infectious disease research and therapeutic drug testing. Here, we describe a zebrafish model for human influenza A virus (IAV infection and show that zebrafish embryos are susceptible to challenge with both influenza A strains APR8 and X-31 (Aichi. Influenza-infected zebrafish show an increase in viral burden and mortality over time. The expression of innate antiviral genes, the gross pathology and the histopathology in infected zebrafish recapitulate clinical symptoms of influenza infections in humans. This is the first time that zebrafish embryos have been infected with a fluorescent IAV in order to visualize infection in a live vertebrate host, revealing a pattern of vascular endothelial infection. Treatment of infected zebrafish with a known anti-influenza compound, Zanamivir, reduced mortality and the expression of a fluorescent viral gene product, demonstrating the validity of this model to screen for potential antiviral drugs. The zebrafish model system has provided invaluable insights into host-pathogen interactions for a range of infectious diseases. Here, we demonstrate a novel use of this species for IAV research. This model has great potential to advance our

  3. Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment.

    Gabor, Kristin A; Goody, Michelle F; Mowel, Walter K; Breitbach, Meghan E; Gratacap, Remi L; Witten, P Eckhard; Kim, Carol H

    2014-11-01

    Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in substantial morbidity, mortality and economic burdens. Prevention and treatment of influenza illness is difficult due to the high mutation rate of the virus, the emergence of new virus strains and increasing antiviral resistance. Animal models of influenza infection are crucial to our gaining a better understanding of the pathogenesis of and host response to influenza infection, and for screening antiviral compounds. However, the current animal models used for influenza research are not amenable to visualization of host-pathogen interactions or high-throughput drug screening. The zebrafish is widely recognized as a valuable model system for infectious disease research and therapeutic drug testing. Here, we describe a zebrafish model for human influenza A virus (IAV) infection and show that zebrafish embryos are susceptible to challenge with both influenza A strains APR8 and X-31 (Aichi). Influenza-infected zebrafish show an increase in viral burden and mortality over time. The expression of innate antiviral genes, the gross pathology and the histopathology in infected zebrafish recapitulate clinical symptoms of influenza infections in humans. This is the first time that zebrafish embryos have been infected with a fluorescent IAV in order to visualize infection in a live vertebrate host, revealing a pattern of vascular endothelial infection. Treatment of infected zebrafish with a known anti-influenza compound, Zanamivir, reduced mortality and the expression of a fluorescent viral gene product, demonstrating the validity of this model to screen for potential antiviral drugs. The zebrafish model system has provided invaluable insights into host-pathogen interactions for a range of infectious diseases. Here, we demonstrate a novel use of this species for IAV research. This model has great potential to advance our understanding of

  4. Drug Repurposing Identifies Inhibitors of Oseltamivir-Resistant Influenza Viruses.

    Bao, Ju; Marathe, Bindumadhav; Govorkova, Elena A; Zheng, Jie J

    2016-03-01

    The neuraminidase (NA) inhibitor, oseltamivir, is a widely used anti-influenza drug. However, oseltamivir-resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir-resistant, alternative therapy options are needed. Herein, we show that a structure-based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir-resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild-type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir-resistance mutation itself caused susceptibility to these drugs. PMID:26833677

  5. Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia

    I.A. Leneva; E.I. Burtseva; S.B. Yatsyshina; I.T. Fedyakina; E.S. Kirillova; E.P. Selkova; Osipova, E.; V. V. Maleev

    2016-01-01

    Background: Antiviral drugs are critical adjuncts to influenza vaccination. This study determined the in vitro susceptibilities of influenza A and B viruses isolated in the 2010–2011 season in Russia to the neuraminidase inhibitor oseltamivir and the hemagglutinin fusion inhibitor umifenovir and clinical efficacy of this antiviral drugs in this season. Methods: The antiviral potency of these drugs against A(H1N1)pdm09 virus in mice was assessed. Importantly, the clinical effectiveness of o...

  6. Identification and genetic analysis of H3N8 subtype influenza viruses isolated from domestic pigeons in Central China.

    Zou, Zhong; Chen, Sunrui; Liu, Ziduo; Jin, Meilin

    2016-02-01

    A novel strain of H3N8 influenza virus was isolated from domestic pigeons during the avian influenza virus (AIV) surveillance in wet markets in Anhui, China, during 2013. The virus was characterized by whole-genome sequencing with subsequent genetic comparison and phylogenetic analysis. Phylogenetic analysis revealed that the NA gene of AIV mapped to the North American lineage, and the remaining seven genes belong to a Eurasian lineage. These findings indicated that this H3N8 virus is a novel nature reassortant virus. Comparison of the hemagglutinin amino acid sequences indicated 9 substitutions. One substitution caused the loss of a potential glycosylation site, and six substitutions were not previously observed in avian H3 isolates. Q226 and T228 at the receptor binding sites suggested that Anhui-08 preferentially binds to a-2,3-linked sialic acid receptors, and the cleavage site sequence showed a low pathogenic feature. Animal experiments further confirmed that A/pigeon/Anhui/08/2013 (H3N8) is low or in pigeons. The results improve our understanding of these viruses as they evolve and also provide important information to aid ongoing risk assessment analyses because these zoonotic influenza viruses continue to circulate and adapt to new hosts. PMID:26611442

  7. Antigenic Drift of A/H3N2/Virus and Circulation of Influenza-Like Viruses During the 2014/2015 Influenza Season in Poland.

    Bednarska, K; Hallmann-Szelińska, E; Kondratiuk, K; Brydak, L B

    2016-01-01

    Morbidity rates of influenza could be greatly reduced due to vaccination. However, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. Their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. In Poland, the 2014/2015 influenza epidemic started in week 5 (January/February) of 2015 and continued until week 17 (April) of 2015. The influenza activity was moderate with the highest incidence of influence-like illness at week 10/2015 (March). During that season, antigenic drift of influenza virus A/H3N2/ occurred causing higher rates of A/H3N2/ infections. Among the 2416 tested specimens, 22.6 % of influenza cases were positive for A/H3N2/, while A/H1N1/pdm09 constituted 14.6 % cases. Influenza A viruses were detected in co-circulation with influenza B viruses; the latter amounted to 34.1 % of all influenza detections. Other detected causes of influenza-like illness consisted of respiratory syncytial virus (RSV), being predominant, and, sporadically, human coronavirus, parainfluenza 1-3, rhinovirus, and adenovirus. Despite low vaccine effectiveness of solely one component, A/H3N2/, the vaccine could mitigate or shorten the length of influenza infection and reduce the number of severe outcomes and mortality. Thus, vaccination against influenza remains the most effective way to prevent illness and possibly fatal outcomes. PMID:26956457

  8. Transmission of highly pathogenic avian influenza H7 virus

    Bos, M.E.H.

    2009-01-01

    Knowledge of the transmission of highly pathogenic avian influenza (HPAI) virus still has gaps, complicating epidemic control. A model was developed to back-calculate the day HPAI virus was introduced into a flock, based on within-flock mortality data of the Dutch HPAI H7N7 epidemic (2003). The method was based on a stochastic epidemic model in which birds move from being susceptible, latently infected and infectious, to death. Our results indicated that two weeks can elapse before a noticeab...

  9. DNA intercalator stimulates influenza transcription and virus replication

    Poon Leo LM

    2011-03-01

    Full Text Available Abstract Influenza A virus uses its host transcription machinery to facilitate viral RNA synthesis, an event that is associated with cellular RNA polymerase II (RNAPII. In this study, various RNAPII transcription inhibitors were used to investigate the effect of RNAPII phosphorylation status on viral RNA transcription. A low concentration of DNA intercalators, such as actinomycin D (ActD, was found to stimulate viral polymerase activity and virus replication. This effect was not observed in cells treated with RNAPII kinase inhibitors. In addition, the loss of RNAPIIa in infected cells was due to the shift of nonphosphorylated RNAPII (RNAPIIa to hyperphosphorylated RNAPII (RNAPIIo.

  10. Complete Genome Sequence of an Avian-Like H4N8 Swine Influenza Virus Discovered in Southern China

    Su, Shuo; Qi, Wen-bao; Chen, Ji-dang; Cao, Nan; Zhu, Wan-jun; Yuan, Li-Guo; Wang, Heng; Zhang, Gui-hong

    2012-01-01

    We report here the complete genomic sequence of an avian-like H4N8 swine influenza virus containing an H5N1 avian influenza virus segment from swine in southern China. Phylogenetic analyses of the sequences of all eight viral RNA segments demonstrated that these are wholly avian influenza viruses of the Asia lineage. To our knowledge, this is the first report of interspecies transmission of an avian H4N8 influenza virus to domestic pigs under natural conditions.

  11. Influenza in migratory birds and evidence of limited intercontinental virus exchange.

    Scott Krauss

    2007-11-01

    Full Text Available Migratory waterfowl of the world are the natural reservoirs of influenza viruses of all known subtypes. However, it is unknown whether these waterfowl perpetuate highly pathogenic (HP H5 and H7 avian influenza viruses. Here we report influenza virus surveillance from 2001 to 2006 in wild ducks in Alberta, Canada, and in shorebirds and gulls at Delaware Bay (New Jersey, United States, and examine the frequency of exchange of influenza viruses between the Eurasian and American virus clades, or superfamilies. Influenza viruses belonging to each of the subtypes H1 through H13 and N1 through N9 were detected in these waterfowl, but H14 and H15 were not found. Viruses of the HP Asian H5N1 subtypes were not detected, and serologic studies in adult mallard ducks provided no evidence of their circulation. The recently described H16 subtype of influenza viruses was detected in American shorebirds and gulls but not in ducks. We also found an unusual cluster of H7N3 influenza viruses in shorebirds and gulls that was able to replicate well in chickens and kill chicken embryos. Genetic analysis of 6,767 avian influenza gene segments and 248 complete avian influenza viruses supported the notion that the exchange of entire influenza viruses between the Eurasian and American clades does not occur frequently. Overall, the available evidence does not support the perpetuation of HP H5N1 influenza in migratory birds and suggests that the introduction of HP Asian H5N1 to the Americas by migratory birds is likely to be a rare event.

  12. Analysis of antigenic variation in equine 2 influenza A viruses.

    Hinshaw, V S; Naeve, C W; Webster, R G; Douglas, A; Skehel, J J; Bryans, J

    1983-01-01

    Influenza outbreaks involving viruses of the H3N8 subtype (equine 2) often occur in vaccinated horses. For this reason, a series of influenza viruses of the H3N8 subtype were examined to determine if antigenic variation could be detected in isolates during the period 1963-81. Antigenic analyses with post-infection ferret sera and monoclonal antibodies showed that the haemagglutinins of recent isolates were antigenically distinguishable from the prototype A/eq/Miami/1/63 and that antigenically distinguishable groups of equine 2 viruses co-circulate in the horse population. Based on these studies, it is recommended that a recent equine strain, A/equine/Fontainebleu/1/79 or A/equine/Kentucky/1/81, serve as an additional prototype strain for this subtype.Antigenic variation in equine 2 viruses may be of epidemiological significance, yet the overall conservation of these strains makes it unlikely that vaccine failures can be attributed solely to antigenic changes in these viruses. A sufficiently potent vaccine, containing a current representative of the most prevalent equine 2 strain, may improve the protection afforded by equine vaccines. PMID:6601538

  13. Cross-reactivity between avian influenza A (H7N9) virus and divergent H7 subtypic- and heterosubtypic influenza A viruses

    Li Guo; Dayan Wang; Hongli Zhou; Chao Wu; Xin Gao; Yan Xiao; Lili Ren; Gláucia Paranhos-Baccalà; Yuelong Shu; Qi Jin; Jianwei Wang

    2016-01-01

    The number of human avian H7N9 influenza infections has been increasing in China. Understanding their antigenic and serologic relationships is crucial for developing diagnostic tools and vaccines. Here, we evaluated the cross-reactivities and neutralizing activities among H7 subtype influenza viruses and between H7N9 and heterosubtype influenza A viruses. We found strong cross-reactivities between H7N9 and divergent H7 subtypic viruses, including H7N2, H7N3, and H7N7. Antisera against H7N2, H...

  14. Pathogenesis of the novel avian-origin influenza A (H7N9) virus Influenza H7N9 virus in human lower respiratory tract

    Chan, LY; Chan, WY; Peiris, JSM; Chan, MCW

    2013-01-01

    Background: As of May 2013, 131 laboratory-confirmed human infections with a novel influenza H7N9 virus had been reported from China. The source of human infection appears to be poultry. There is so far no evidence of sustained human-to-human transmission. Genetic analysis revealed that all eight gene segments of H7N9 were of avian origin; six internal gene segments from avian influenza H7N9 viruses, while hemagglutinin and neuraminidase genes were derived from influenza viruses c...

  15. Molecular epidemiology and phylogenetic analyses of influenza B virus in Thailand during 2010 to 2014.

    Nipaporn Tewawong

    Full Text Available Influenza B virus remains a major contributor to the seasonal influenza outbreak and its prevalence has increased worldwide. We investigated the epidemiology and analyzed the full genome sequences of influenza B virus strains in Thailand between 2010 and 2014. Samples from the upper respiratory tract were collected from patients diagnosed with influenza like-illness. All samples were screened for influenza A/B viruses by one-step multiplex real-time RT-PCR. The whole genome of 53 influenza B isolates were amplified, sequenced, and analyzed. From 14,418 respiratory samples collected during 2010 to 2014, a total of 3,050 tested positive for influenza virus. Approximately 3.27% (471/14,418 were influenza B virus samples. Fifty three isolates of influenza B virus were randomly chosen for detailed whole genome analysis. Phylogenetic analysis of the HA gene showed clusters in Victoria clades 1A, 1B, 3, 5 and Yamagata clades 2 and 3. Both B/Victoria and B/Yamagata lineages were found to co-circulate during this time. The NA sequences of all isolates belonged to lineage II and consisted of viruses from both HA Victoria and Yamagata lineages, reflecting possible reassortment of the HA and NA genes. No significant changes were seen in the NA protein. The phylogenetic trees generated through the analysis of the PB1 and PB2 genes closely resembled that of the HA gene, while trees generated from the analysis of the PA, NP, and M genes showed similar topology. The NS gene exhibited the pattern of genetic reassortment distinct from those of the PA, NP or M genes. Thus, antigenic drift and genetic reassortment among the influenza B virus strains were observed in the isolates examined. Our findings indicate that the co-circulation of two distinct lineages of influenza B viruses and the limitation of cross-protection of the current vaccine formulation provide support for quadrivalent influenza vaccine in this region.

  16. Cyclophilin E functions as a negative regulator to influenza virus replication by impairing the formation of the viral ribonucleoprotein complex.

    Zengfu Wang

    Full Text Available BACKGROUND: The nucleoprotein (NP of influenza A virus is a multifunctional protein that plays a critical role in the replication and transcription of the viral genome. Therefore, examining host factors that interact with NP may shed light on the mechanism of host restriction barriers and the tissue tropism of influenza A virus. Here, Cyclophilin E (CypE, a member of the peptidyl-propyl cis-trans isomerase (PPIase family, was found to bind to NP and inhibit viral replication and transcription. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, CypE was found to interact with NP but not with the other components of the viral ribonucleoprotein complex (VRNP: PB1, PB2, and PA. Mutagenesis data revealed that the CypE domain comprised of residues 137-186 is responsible for its binding to NP. Functional analysis results indicated that CypE is a negative regulator in the influenza virus life cycle. Furthermore, knock-down of CypE resulted in increased levels of three types of viral RNA, suggesting that CypE negatively affects viral replication and transcription. Moreover, up-regulation of CypE inhibited the activity of influenza viral polymerase. We determined that the molecular mechanism by which CypE negatively regulates influenza virus replication and transcription is by interfering with NP self-association and the NP-PB1 and NP-PB2 interactions. CONCLUSIONS/SIGNIFICANCE: CypE is a host restriction factor that inhibits the functions of NP, as well as viral replication and transcription, by impairing the formation of the vRNP. The data presented here will help us to better understand the molecular mechanisms of host restriction barriers, host adaptation, and tissue tropism of influenza A virus.

  17. Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding.

    Henry Memczak

    Full Text Available Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.

  18. Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding.

    Memczak, Henry; Lauster, Daniel; Kar, Parimal; Di Lella, Santiago; Volkmer, Rudolf; Knecht, Volker; Herrmann, Andreas; Ehrentreich-Förster, Eva; Bier, Frank F; Stöcklein, Walter F M

    2016-01-01

    Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing. PMID:27415624

  19. Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus.

    Naeve, C W; Hinshaw, V S; Webster, R G

    1984-01-01

    Avian influenza virus reassortants containing human influenza virus hemagglutinins do not replicate in ducks. Two mutations in the receptor-binding site of a human hemagglutinin at residues 226 and 228 allowed replication in ducks. The mutations resulted in a receptor-binding-site sequence identical to the known avian influenza virus sequences.

  20. Searching of Main Cause Leading to Severe Influenza A Virus Mutations and Consequently to Influenza Pandemics/Epidemics

    Guang Wu

    2005-01-01

    Full Text Available The unpredictable mutations in the proteins from influenza A virus lead to the great difficulty in prevention of possible outbreak of bird flu and pandemic/epidemic of influenza. This unpredictability is due to the fact that we know little about the causes that lead to the mutations. In three of our recent studies on the hemagglutinins from influenza A virus, we unintentionally noticed the periodicity of mutations in hemagglutinins similar to the periodicity of sunspot. We calculated the amino-acid pair predictability and amino-acid distribution rank, which are developed by us over last several years and can numerically present the evolution of proteins in question, of 1217 full-length hemagglutinins from influenza A viruses. We then used the fast Fourier transform to determine the periodicity of mutations in the hemagglutinins. We compare the periodicities of mutations in influenza A virus hemagglutinins with those of solar and galactic cosmic rays and find a main periodicity of the mutations identical to that of sunspot and neutron rate (11 years/circle. Then we plot the sunspot number with respect to the historical pandemics/epidemics/non-pandemic new strains over last three centuries and compare the recorded sunspots with the historical pandemics before 1700. Both show a good agreement between sunspot activity and influenza related events. As the histories of Sun and galaxy are incomparably much longer than the history of influenza virus, the only logical deduction is that the hemagglutinin periodicities, which are identical to the periodicities of solar and galactic cosmic rays, are attribute to the solar and galactic activity. As the hemagglutinin is a sample of influenza A virus, we can logically deduce the role of migratory wild birds on the outbreak of bird flu and influenza, that is, cosmic rays are heading towards the polar regions, where more mutations occur in influenza A virus either within the wild birds or in their living

  1. Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene

    Reid, Ann H.; Fanning, Thomas G.; Hultin, Johan V.; Taubenberger, Jeffery K.

    1999-01-01

    The “Spanish” influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report the complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Influenza RNA for the analysis was isolated from a formalin-fixed, paraffin-embedded lung tissue sample prepared during the autopsy of a victim of the influenza pandemic in 1918. Influenza RNA was also isolated from lung tissue samples from two add...

  2. Influenza Virus Infection Decreases Tracheal Mucociliary Velocity and Clearance of Streptococcus pneumoniae

    Pittet, Lynnelle A.; Hall-Stoodley, Luanne; Rutkowski, Melanie R.; Harmsen, Allen G.

    2009-01-01

    Influenza virus infections increase susceptibility to secondary bacterial infections, such as pneumococcal pneumonia, resulting in increased morbidity and mortality. Influenza-induced tissue damage is hypothesized to increase susceptibility to Streptococcus pneumoniae infection by increasing adherence to the respiratory epithelium. Using a mouse model of influenza infection followed by S. pneumoniae infection, we found that an influenza infection does not increase the number of pneumococci in...

  3. Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice

    Cummins, Nathan W.; Weaver, Eric A.; May, Shannon M.; Croatt, Anthony J.; Foreman, Oded; Kennedy, Richard B.; Poland, Gregory A.; Michael A. Barry; Nath, Karl A.; Badley, Andrew D.

    2012-01-01

    Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genom...

  4. Asthma and influenza virus infection:focusing on cell death and stress pathways in influenza virus replication.

    Behzad Yeganeh

    2013-03-01

    Full Text Available Asthma is one of the fastest growing syndromes in many countries and is adding a huge cost to the health care system. Increasing reports have linked airway infectious diseases to asthma. Influenza is one of the most serious airway infectious diseases and in recent years there have been some serious influenza virus pandemics which caused increased fatality in numerous different populations. Diverse host response pathways during virus infection have been identified, including different cell death and survival pathways. These pathways include1 programmed cell death I (apoptosis, 2 programmed cell death II (autophagy, and 3 endoplasmic reticulum stress with subsequent unfolded protein response (UPR. There has been extensive research on the regulatory roles of these pathways during the influenza virus life cycle. These studies address the benefits of enhancing or inhibiting these pathways on viral replication. Here we review the most recent and significant knowledge in this area for possible  benefits  to  clinicians and  basic  scientist researchers  in  different  areas  of  the respiratory and virology sciences.

  5. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair

  6. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    Manning, Casey M. [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Johnston, Carl J. [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (United States); Reed, Christina K. [Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (United States); Lawrence, B. Paige [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York (United States); Williams, Jacqueline P. [Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York (United States); Finkelstein, Jacob N., E-mail: Jacob_Finkelstein@urmc.rochester.edu [Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York (United States); Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (United States); Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York (United States)

    2013-05-01

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

  7. Receptor Characterization and Susceptibility of Cotton Rats to Avian and 2009 Pandemic Influenza Virus Strains

    Blanco, Jorge C. G.; Pletneva, Lioubov M; Wan, Hongquan; Araya, Yonas; Angel, Matthew; Oue, Raymonde O.; Sutton, Troy C.; Perez, Daniel R

    2013-01-01

    Animal influenza viruses (AIVs) are a major threat to human health and the source of pandemic influenza. A reliable small-mammal model to study the pathogenesis of infection and for testing vaccines and therapeutics against multiple strains of influenza virus is highly desirable. We show that cotton rats (Sigmodon hispidus) are susceptible to avian and swine influenza viruses. Cotton rats express α2,3-linked sialic acid (SA) and α2,6-linked SA residues in the trachea and α2,6-linked SA residu...

  8. A simple and rapid characterization of influenza virus isolates by monoclonal antibodies in radioimmunoassay

    Radioimmunoassay is described with infectious allantoic fluid directly bound to solid phase, suitable for the detection and further characterization of influenza virus isolates. This simple and rapid method was applied for the description of isolates obtained from different regions of Czechoslovakia during the influenza epidemic in 1983. The results confirmed that all 13 examined isolates represented influenza A viruses possessing H3 subtype haemagglutinin very similar to haemagglutinin of influenza viruses A/Bangkok/1/79 (H3N2), A/Belgium/2/81 (H3N2) and A/Philippines/2/82 (H3N2). (author)

  9. Structure and Function of the NS1 Protein of Influenza A Virus

    Dongzi LIN; Jingfang LAN; Zhizhen ZHANG

    2007-01-01

    The avian influenza A virus currently prevailing in Asia causes fatal pneumonia and multiple organ failure in birds and humans.Despite intensive research,understanding of the characteristics of influenza A virus that determine its virulence is incomplete.NS1A protein,a non-structural protein of influenza A virus,was reported to contribute to its pathogenicity and virulence.NS1A protein is a multifunctional protein that plays a significant role in resisting the host antiviral response during the influenza infection.This review briefly outlines the current knowledge on the structure and function of the NS1A protein.

  10. Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014–2015

    Lee, Dong-Hun; Bahl, Justin; Torchetti, Mia Kim; Killian, Mary Lea; Ip, Hon S.; DeLiberto, Thomas J.

    2016-01-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses. PMID:27314845

  11. Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014-2015.

    Lee, Dong-Hun; Bahl, Justin; Torchetti, Mia Kim; Killian, Mary Lea; Ip, Hon S; DeLiberto, Thomas J; Swayne, David E

    2016-07-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses. PMID:27314845

  12. Carbohydrate determinants in ferret conjunctiva are affected by infection with influenza H1N1 virus

    Kirkeby, Svend; Martel, Cyril; Aasted, Bent; Vorum, Henrik

    2013-01-01

    Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium.......Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium....

  13. Highly pathogenic avian influenza viruses and generation of novel reassortants,United States, 2014–2015

    Dong-Hun Lee; Justin Bahl; Mia Kim Torchetti; Mary Lea Killian; Ip, Hon S.; David E Swayne

    2016-01-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses.

  14. Revelation of Influencing Factors in Overall Codon Usage Bias of Equine Influenza Viruses

    Bhatia, Sandeep; Sood, Richa; Selvaraj, Pavulraj

    2016-01-01

    Equine influenza viruses (EIVs) of H3N8 subtype are culprits of severe acute respiratory infections in horses, and are still responsible for significant outbreaks worldwide. Adaptability of influenza viruses to a particular host is significantly influenced by their codon usage preference, due to an absolute dependence on the host cellular machinery for their replication. In the present study, we analyzed genome-wide codon usage patterns in 92 EIV strains, including both H3N8 and H7N7 subtypes by computing several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis disclosed bias of preferred synonymous codons towards A/U-ended codons. The overall codon usage bias in EIVs was slightly lower, and mainly affected by the nucleotide compositional constraints as inferred from the RSCU and effective number of codon (ENc) analysis. Our data suggested that codon usage pattern in EIVs is governed by the interplay of mutation pressure, natural selection from its hosts and undefined factors. The H7N7 subtype was found less fit to its host (horse) in comparison to H3N8, by possessing higher codon bias, lower mutation pressure and much less adaptation to tRNA pool of equine cells. To the best of our knowledge, this is the first report describing the codon usage analysis of the complete genomes of EIVs. The outcome of our study is likely to enhance our understanding of factors involved in viral adaptation, evolution, and fitness towards their hosts. PMID:27119730

  15. Third Wave of Influenza A(H7N9) Virus from Poultry, Guangdong Province, China, 2014-2015.

    Xie, Shumin; Jia, Weixin; Lin, Yicun; Xing, Kaixiang; Ren, Xingxing; Qi, Wenbao; Liao, Ming

    2015-09-01

    Fourteen influenza A(H7N9) viruses were isolated from poultry or the environment in live poultry markets in Guangdong Province, China during 2014-2015. Phylogenetic analysis showed that all viruses were descended from viruses of the second wave of influenza A(H7N9) virus infections during 2013. These viruses can be divided into 2 branches. PMID:26291620

  16. Ultrasensitive detection of influenza viruses with a glycan-based impedimetric biosensor

    Hushegyi, András; Pihíková, Dominika; Bertók, Tomáš; Adam, Vojtech; Kizek, René; Tkac, Jan

    2015-01-01

    An ultrasensitive impedimetric glycan-based biosensor for reliable and selective detection of inactivated, but intact influenza viruses H3N2 was developed. Such glycan-based approach has a distinct advantage over antibody-based detection of influenza viruses since glycans are natural viral receptors with a possibility to selectively distinguish between potentially pathogenic influenza subtypes by the glycan-based biosensors. Build-up of the biosensor was carefully optimized with atomic force ...

  17. Modelling the innate immune response against avian influenza virus in chicken

    Hagenaars, T.J.; Fischer, E.A.J.; Jansen, C.A.; Rebel, J.M.J.; Spekreijse, D.; Vervelde, L.; Backer, J.A.; Jong, de M.C.M.; Koets, A.P.

    2016-01-01

    At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α,

  18. Absence of Pandemic H1N1 Influenza A Virus in Fresh Pork

    Pigs experimentally infected with pandemic 2009 H1N1 influenza A virus developed respiratory disease; however, there was no evidence for systemic disease to suggest that pork from pigs infected with H1N1 influenza would contain infectious virus. These findings support the WHO recommendation that po...

  19. Enhanced Pneumonia With Pandemic 2009 A/H1N1 Swine Influenza Virus in Pigs

    Introduction. Swine influenza A viruses (SIV) in the major swine producing regions of North America consist of multiple subtypes of endemic H1N1, H1N2, and H3N2 derived from swine, avian and human influenza viruses with a triple reassortant internal gene (TRIG) constellation (1). Genetic drift and r...

  20. Influenza A virus infections in land birds, People's Republic of China

    Peterson, A.T.; Bush, S.E.; Spackman, Erica; Swayne, D.E.; Ip, H.S.

    2008-01-01

    Water birds are considered the reservoir for avian influenza viruses. We examined this assumption by sampling and real-time reverse transcription-PCR testing of 939 Asian land birds of 153 species. Influenza A infection was found, particularly among migratory species. Surveillance programs for monitoring spread of these viruses need to be redesigned.

  1. Lymphocyte responses in the lungs of vaccinated pigs following homologous and heterologous influenza A virus challenge.

    Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of non-neutralizing antibody that is cross-reactive to the chal...

  2. Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes

    Gannagé, Monique; Dormann, Dorothee; Albrecht, Randy;

    2009-01-01

    demonstrate that influenza A virus inhibits macroautophagy, a cellular process known to be manipulated by diverse pathogens. Influenza A virus infection causes accumulation of autophagosomes by blocking their fusion with lysosomes, and one viral protein, matrix protein 2, is necessary and sufficient for this...

  3. Influenza A Virus Infections in Land Birds, People’s Republic of China

    Peterson, A. Townsend; Bush, Sarah E.; Spackman, Erica; Swayne, David E.; Ip, Hon S.

    2008-01-01

    Water birds are considered the reservoir for avian influenza viruses. We examined this assumption by sampling and real-time reverse transcription–PCR testing of 939 Asian land birds of 153 species. Influenza A infection was found, particularly among migratory species. Surveillance programs for monitoring spread of these viruses need to be redesigned.

  4. Highly Pathogenic Avian Influenza Virus A (H7N3) in Domestic Poultry, Saskatchewan, Canada, 2007

    Berhane, Yohannes; Hisanaga, Tamiko; Kehler, Helen; Neufeld, James; Manning, Lisa; Argue, Connie; Handel, Katherine; Hooper-McGrevy, Kathleen; Jonas, Marilyn; Robinson, John; Webster, Robert G.; Pasick, John

    2009-01-01

    Epidemiologic, serologic, and molecular phylogenetic methods were used to investigate an outbreak of highly pathogenic avian influenza on a broiler breeding farm in Saskatchewan, Canada. Results, coupled with data from influenza A virus surveillance of migratory waterfowl in Canada, implicated wild birds as the most probable source of the low pathogenicity precursor virus.

  5. Outbreaks of Influenza A Virus in Farmed Mink (Neovison vison) in Denmark: Molecular characterization of the involved viruses

    Larsen, Lars Erik; Breum, Solvej Østergaard; Trebbien, Ramona; Bradstad, Karolina; Nielsen, Lars Peter; Chriél, Mariann; Jensen, Trine Hammer; Hjulsager, Charlotte Kristiane; Handberg, Kurt; Jørgensen, Poul Henrik; Harslund, Jakob le Fèvre; Rangstrup-Christensen, Lena; Pedersen, Bjarne; Hammer, Anne Sofie

    or was circulating in Danish pigs. In 2010 and 2011, influenza virus was again diagnosed in diseased mink in a few farms. The genetic typing showed that the virus was similar to the pandemic H1N1 virus circulating in humans and swine. The H3N2 virus was not detected in 2010 and 2011. Taken together...

  6. Influenza virus surveillance in Argentina during the 2012 season: antigenic characterization, genetic analysis and antiviral susceptibility.

    Benedetti, E; Daniels, R S; Pontoriero, A; Russo, M; Avaro, M; Czech, A; Campos, A; Periolo, N; Gregory, V; McCauley, J W; Baumeister, E G

    2016-03-01

    The activity and circulation of influenza viruses in Argentina was studied during 2012 as part of the Argentinean Surveillance for Influenza and other Respiratory Viruses, in the context of Global Influenza Surveillance. The antigenicity and molecular characteristics of haemagglutinins (HA) of circulating influenza A and B viruses were analysed to assess the emergence of virus variants. Susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay and results were backed-up by sequencing of the neuraminidase (NA) genes. During the 2012 season, influenza virus circulation in Argentina was detected from weeks 24 to 51. The HA sequences of the studied A(H1N1)pdm09 subtype viruses segregated in a different genetic group compared to those identified during the 2009 pandemic, although they were still closely related antigenically to the vaccine virus A/California/07/2009. The HA sequences of the A(H3N2) viruses analysed fell into the A/Victoria/208/2009 clade, genetic group 3C. A mixed circulation of virus variants belonging to B/Victoria and B/Yamagata lineages was detected, with B/Victoria being dominant. All viruses tested were sensitive to oseltamivir and zanamivir except one. This isolate, an A(H1N1)pdm09 virus possessing the substitution NA-N295S, showed highly reduced inhibition by oseltamivir and reduced inhibition by zanamivir. Virological and epidemiological surveillance remains critical for detection of evolving influenza viruses. PMID:26345289

  7. Dynamical correlations in the escape strategy of Influenza A virus

    Taggi, L.; Colaiori, F.; Loreto, V.; Tria, F.

    2013-03-01

    The evolutionary dynamics of human Influenza A virus presents a challenging theoretical problem. An extremely high mutation rate allows the virus to escape, at each epidemic season, the host immune protection elicited by previous infections. At the same time, at each given epidemic season a single quasi-species, that is a set of closely related strains, is observed. A non-trivial relation between the genetic (i.e., at the sequence level) and the antigenic (i.e., related to the host immune response) distances can shed light into this puzzle. In this paper we introduce a model in which, in accordance with experimental observations, a simple interaction rule based on spatial correlations among point mutations dynamically defines an immunity space in the space of sequences. We investigate the static and dynamic structure of this space and we discuss how it affects the dynamics of the virus-host interaction. Interestingly we observe a staggered time structure in the virus evolution as in the real Influenza evolutionary dynamics.

  8. The role of fusion activity of influenza A viruses in their biological properties.

    Jakubcová, L; Hollý, J; Varečková, E

    2016-06-01

    Influenza A viruses (IAVs) cause acute respiratory infections of humans, which are repeated yearly. Human IAV infections are associated with significant morbidity and mortality and therefore they represent a serious health problem. All human IAV strains are originally derived from avian IAVs, which, after their adaptation to humans, can spread in the human population and cause pandemics with more or less severe course of the disease. Presently, however, the potential of avian IAV to infect humans and to cause the disease cannot be predicted. Many studies are therefore focused on factors influencing the virulence and pathogenicity of IAV viruses in a given host. The virus-host interaction starts by virus attachment via the envelope glycoprotein hemagglutinin (HA) to the receptors on the cell surface. In addition to receptor binding, HA mediates also the fusion of viral and endosomal membranes, which follows the virus endocytosis. The fusion potential of HA trimer, primed by proteolytic cleavage, is activated by low pH in endosomes, resulting in HA refolding into the fusion-active form. The HA conformation change is predetermined by its 3-D structure, is pH-dependent, irreversible and strain-specific. The process of fusion activation of IAV hemagglutinin is crucial for virus entry into the cell and for the ability of the virus to replicate in the host. Here we discuss the known data about the characteristics of fusion activation of HA in relation to IAV virulence and pathogenicity. PMID:27265461

  9. Vaccination of influenza a virus decreases transmission rates in pigs

    Romagosa Anna

    2011-12-01

    Full Text Available Abstract Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R of infection (i.e. the number of secondary infections caused by an infectious individual using a deterministic Susceptible-Infectious-Recovered (SIR model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i non-vaccinated (NV, (ii vaccinated with a heterologous vaccine (HE, and (iii vaccinated with a homologous inactivated vaccine (HO. The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p R (95%CI was 1 (0.39-2.09 and 0 for the HE and the HO groups respectively, compared to an Ro value of 10.66 (6.57-16.46 in NV pigs (p

  10. Control of mucosal virus infection by influenza nucleoprotein-specific CD8+ cytotoxic T lymphocytes

    Couch Robert B

    2007-06-01

    Full Text Available Abstract Background MHC class I-restricted CD8+ cytotoxic T lymphocytes (CTL are thought to play a major role in clearing virus and promoting recovery from influenza infection and disease. This has been demonstrated for clearance of influenza virus from the lungs of infected mice. However, human influenza infection is primarily a respiratory mucosal infection involving the nasopharynx and tracheobronchial tree. The role of CD8+ CTL directed toward the influenza nucleoprotein (NP in defense against influenza virus infection at the respiratory mucosa was evaluated in two separate adoptive transfer experiments. Methods Influenza nucleoprotein (NP-specific CD8+ CTL were generated from splenocytes obtained from Balb/c mice previously primed with influenza A/Taiwan/1/86 (H1N1 infection or with influenza A/PR/8/34 (H1N1-derived NP plasmid DNA vaccine followed by infection with A/Hong Kong/68 (H3N2 virus. After in vitro expansion by exposure to an influenza NP-vaccinia recombinant, highly purified CD8+ T cells exhibited significant lysis in vitro of P815 target cells infected with A/Hong Kong/68 (H3N2 virus while the CD8- fraction (CD4+ T cells, B cells and macrophages had no CTL activity. Purified CD8+ and CD8- T cells (1 × 107 were injected intravenously or interperitoneally into naive mice four hours prior to intranasal challenge with A/HK/68 (H3N2 virus. Results The adoptively transferred NP-vaccinia-induced CD8+ T cells caused significant reduction of virus titers in both the lungs and nasal passages when compared to CD8- cells. Neither CD8+ nor CD8- T cells from cultures stimulated with HIV gp120-vaccinia recombinant reduced virus titers. Conclusion The present data demonstrate that influenza NP-specific CD8+ CTL can play a direct role in clearance of influenza virus from the upper respiratory mucosal surfaces.

  11. A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

    Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

    2014-01-01

    During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens. PMID:24480060

  12. Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus

    O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J.; Subbarao, Kanta

    2014-01-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and hu...

  13. Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques.

    Shichinohe, Shintaro; Itoh, Yasushi; Nakayama, Misako; Ozaki, Hiroichi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-06-01

    The outbreak of H7N9 low pathogenic avian influenza viruses in China has attracted attention to H7 influenza virus infection in humans. Since we have shown that the pathogenicity of H1N1 and H5N1 influenza viruses in macaques was almost the same as that in humans, we compared the pathogenicities of H7 avian influenza viruses in cynomolgus macaques via intranasal and conjunctival inoculation, which mimics natural infection in humans. H7N9 virus, as well as H7N7 highly pathogenic avian influenza virus, showed more efficient replication and higher pathogenicity in macaques than did H7N1 and H7N3 highly pathogenic avian influenza viruses. These results are different from pathogenicity in chickens as reported previously. Therefore, our results obtained in macaques help to estimate the pathogenicity of H7 avian influenza viruses in humans. PMID:26994587

  14. Reassortment compatibility between PB1, PB2, and HA genes of the two influenza B virus lineages in mammalian cells

    Kim, Jin Il; Lee, Ilseob; Park, Sehee; Bae, Joon-Yong; Yoo, Kirim; Lemey, Philippe; Park, Mee Sook; Song, Jin-Won; Kee, Sun-Ho; Song, Ki-Joon; Park, Man-Seong

    2016-01-01

    In addition to influenza A subtypes, two distinct lineages of influenza B virus also cause seasonal epidemics to humans. Recently, Dudas et al. have done evolutionary analyses of reassortment patterns of the virus and suggested genetic lineage relationship between PB1, PB2, and HA genes. Using genetic plasmids and reassortant viruses, we here demonstrate that a homologous lineage PB1-PB2 pair exhibits better compatibility than a heterologous one and that the lineage relationship between PB1 and HA is more important for viral replication than that between PB2 and HA. However, co-adaptation of PB1-PB2-HA genes appears to be affected by complete gene constellation. PMID:27270757

  15. Characterization of H7N2 Avian Influenza Virus in Wild Birds and Pikas in Qinghai-Tibet Plateau Area

    Su, Shuo; Xing, Gang; Wang, Junhua; Li, Zengkui; Gu, Jinyan; Yan, Liping; Lei, Jing; Ji, Senlin; Hu, Boli; Gray, Gregory C.; Yan, Yan; Zhou, Jiyong

    2016-01-01

    Qinghai Lake is a major migrating bird breeding site that has experienced several recent highly pathogenic avian influenza virus (HPAIV) epizootics. From 2006 to 2009 we studied Qinghai’s wild birds and pikas for evidence of AIV infections. We sampled 941 healthy wild animals and isolated seventeen H7N2 viruses (eight from pikas and nine from wild birds). The H7N2 viruses were phylogenetically closely related to each other and to viruses isolated in Hong Kong in the 1970s. We determined the pathogenicity of the H7N2 viruses by infecting chickens and mice. Our results suggest that pikas might play an important role in the ecology of AIVs, acting as intermediate hosts in which viruses become more adapted to mammals. Our findings of AI infection in pikas are consistent with previous observations and raise the possibility that pikas might play a previously unrecognized role in the ecology of AIVs peridomestic aquatic environments. PMID:27553660

  16. New influenza A virus reassortments have been found in Danish swine in 2011

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona;

    2012-01-01

    In 2011 a passive surveillance for influenza A virus was conducted in Danish swine. Tested samples were clinical samples from affected pigs submitted to the Danish National Veterinary Institute for swine influenza virus detection. In total 713 samples from 276 herds were analysed and about 24% of...... genes from the pandemic H1N1 virus. This study contribute significantly to our knowledge of the epidemiology of swine influenza A virus circulating in Danish swine and the potential role of swine in the emergence of novel reassortant viruses.......In 2011 a passive surveillance for influenza A virus was conducted in Danish swine. Tested samples were clinical samples from affected pigs submitted to the Danish National Veterinary Institute for swine influenza virus detection. In total 713 samples from 276 herds were analysed and about 24% of...... the samples were positive for swine influenza virus. All influenza positive samples were tested for the H1N1pdm09 virus by a real time RT-PCR assay specific for the pandemic HA gene and 26% of the samples were positive. Subtyping of 90 samples by sequencing revealed the presence of; i) H1N1 “avian...

  17. Swine Influenza Viruses – Evolution and Zoonotic Potential

    Fobian, Kristina

    Influenza A virus (IAV) is an important respiratory pathogen with a broad host range. The natural reservoir for IAV is waterfowls, but both human and swine are considered natural hosts. During the past century IAV has caused severe pandemics as well as seasonal epidemics in the human population. In...... mixing vessels of new IAVs. Furthermore, transmission of IAVs from swine to human and vice versa has been documented on several occasions and further classifies this virus as a highly important zoonosis. This aspect enhances the possibility of the formation and establishment of new and potentially more...... virulent viruses with the capacity to cause severe pandemics. Therefore, it is important to gain a deeper understanding of the evolution of SIVs, their zoonotic potential as well as host-range characteristics and this PhD project aimed at elucidating parts of these important points. The PhD thesis begins...

  18. Targeting Importin-α7 as a Therapeutic Approach against Pandemic Influenza Viruses.

    Resa-Infante, Patricia; Paterson, Duncan; Bonet, Jaume; Otte, Anna; Oliva, Baldo; Fodor, Ervin; Gabriel, Gülsah

    2015-09-01

    Viral drug resistance is believed to be less likely to occur if compounds are directed against cellular rather than viral proteins. In this study, we analyzed the feasibility of a crucial viral replication factor, namely, importin-α7, as a cellular drug target to combat pandemic influenza viruses. Surprisingly, only five viral lung-to-lung passages were required to achieve 100% lethality in importin-α7⁻/⁻ mice that otherwise are resistant. Viral escape from importin-α7 requirement was mediated by five mutations in the viral ribonucleoprotein complex and the surface glycoproteins. Moreover, the importin-α7⁻/⁻ mouse-adapted strain became even more virulent for wild-type mice than the parental strain. These studies show that targeting host proteins may still result in viral escape by alternative pathways, eventually giving rise to even more virulent virus strains. Thus, therapeutic intervention strategies should consider a multitarget approach to reduce viral drug resistance. IMPORTANCE Here, we investigated the long-standing hypothesis based on in vitro studies that viral drug resistance occurrence is less likely if compounds are directed against cellular rather than viral proteins. Here, we challenged this hypothesis by analyzing, in an in vivo animal model, the feasibility of targeting the cellular factor importin-α7, which is crucial for human influenza virus replication and pathogenesis, as an efficient antiviral strategy against pandemic influenza viruses. In summary, our studies suggest that resistance against cellular factors is possible in vivo, and the emergence of even more virulent viral escape variants calls for particular caution. Thus, therapeutic intervention strategies should consider a multitarget approach using compounds against viral as well as cellular factors to reduce the risk of viral drug resistance and potentially increased virulence. PMID:26085167

  19. Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part II: Future compounds against influenza virus.

    Gasparini, R; Amicizia, D; Lai, P L; Bragazzi, N L; Panatto, D

    2014-12-01

    In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed. In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in mono-therapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients. To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories. PMID:26137785

  20. The study of side-effects caused by γ-ray inactivation of influenza virus in producing an influenza virus vaccine

    Inactivation of influenza virus by 60Co-γ-rays in producing an influenza virus vaccine leads to yellowing of the pre-- paration and a decrease in its opalescence. The change in optic properties was only observed at a dose of 5 Gy and higher with sucrose and protein stabilizer simultaneosly present in the solution. It was established that the formation of stained compounds is the result of a radiochemical interaction between intermediate products of radiolysis of these components

  1. Persistence of Highly Pathogenic Avian Influenza H5N1 Virus Defined by Agro-Ecological Niche

    Hogerwerf, Lenny; Wallace, Rob G.; Ottaviani, Daniela; Slingenbergh, Jan; Prosser, Diann; Bergmann, Luc; Gilbert, Marius

    2010-01-01

    The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with...

  2. Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells

    LI Hong; Xiang, Zheng; Feng, Ting; Li, Jinrong; Liu, Yinping; Fan, Yingying; Lu, Qiao; Yin, Zhongwei; Yu, Meixing; Shen, Chongyang; Tu, Wenwei

    2013-01-01

    γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their under...

  3. Infection of differentiated porcine airway epithelial cells by influenza virus: differential susceptibility to infection by porcine and avian viruses.

    Darsaniya Punyadarsaniya

    Full Text Available BACKGROUND: Swine are important hosts for influenza A viruses playing a crucial role in the epidemiology and interspecies transmission of these viruses. Respiratory epithelial cells are the primary target cells for influenza viruses. METHODOLOGY/PRINCIPAL FINDINGS: To analyze the infection of porcine airway epithelial cells by influenza viruses, we established precision-cut lung slices as a culture system for differentiated respiratory epithelial cells. Both ciliated and mucus-producing cells were found to be susceptible to infection by swine influenza A virus (H3N2 subtype with high titers of infectious virus released into the supernatant already one day after infection. By comparison, growth of two avian influenza viruses (subtypes H9N2 and H7N7 was delayed by about 24 h. The two avian viruses differed both in the spectrum of susceptible cells and in the efficiency of replication. As the H9N2 virus grew to titers that were only tenfold lower than that of a porcine H3N2 virus this avian virus is an interesting candidate for interspecies transmission. Lectin staining indicated the presence of both α-2,3- and α-2,6-linked sialic acids on airway epithelial cells. However, their distribution did not correlate with pattern of virus infection indicating that staining by plant lectins is not a reliable indicator for the presence of cellular receptors for influenza viruses. CONCLUSIONS/SIGNIFICANCE: Differentiated respiratory epithelial cells significantly differ in their susceptibility to infection by avian influenza viruses. We expect that the newly described precision-cut lung slices from the swine lung are an interesting culture system to analyze the infection of differentiated respiratory epithelial cells by different pathogens (viral, bacterial and parasitic ones of swine.

  4. Bioaerosol sampling for the detection of aerosolized influenza virus

    Blachere, Francoise M.; Lindsley, William G.; Slaven, James E.; Green, Brett J.; Anderson, Stacey E.; Chen, Bean T.; Beezhold, Don H.

    2007-01-01

    Background Influenza virus was used to characterize the efficacy of a cyclone‐based, two‐stage personal bioaerosol sampler for the collection and size fractionation of aerosolized viral particles. Methods A Collison single‐jet nebulizer was used to aerosolize the attenuated FluMist® vaccine into a calm‐air settling chamber. Viral particles were captured with bioaerosol samplers that utilize 2 microcentrifuge tubes to collect airborne particulates. The first tube (T1) collects particles greater than 1.8 μm in diameter, while the second tube (T2) collects particles between 1.0 and 1.8 μm, and the back‐up filter (F) collects submicron particles. Following aerosolization, quantitative PCR was used to detect and quantify H1N1 and H3N2 influenza strains. Results Based on qPCR results, we demonstrate that aerosolized viral particles were efficiently collected and separated according to aerodynamic size using the two‐stage bioaerosol sampler. Most viral particles were collected in T2 (1‐1.8 μm) and on the back‐up filter (< 1 μm) of the bioaerosol sampler. Furthermore, we found that the detection of viral particles with the two‐stage sampler was directly proportional to the collection time. Consequently, viral particle counts were significantly greater at 40 minutes in comparison to 5, 10 and 20 minute aerosol collection points. Conclusions Due to a lack of empirical data, aerosol transmission of influenza is often questioned. Using FluMist®, we demonstrated that a newly developed bioaerosol sampler is able to recover and size fractionate aerosolized viral particles. This sampler should be an important tool for studying viral transmission in clinical settings and may significantly contribute towards understanding the modes of influenza virus transmission. PMID:19453416

  5. An Overview of the Highly Pathogenic H5N1 Influenza Virus

    Jingchuan Yin; Shi Liu; Ying Zhu

    2013-01-01

    Since the first human case of H5N1 avian influenza virus infection was reported in 1997,this highly pathogenic virus has infected hundreds of people around the world and resulted in many deaths.The ability of H5N1 to cross species boundaries,and the presence of polymorphisms that enhance virulence,present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus.This review summarizes the current understanding of,and recent research on,the avian influenza H5N1 virus,including transmission,virulence,pathogenesis,clinical characteristics,treatment and prevention.

  6. New avian influenza A virus subtype combination H5N7 identified in Danish mallard ducks

    Bragstad, K.; Jørgensen, Poul Henrik; Handberg, Kurt; Mellergaard, Stig; Corbet, S.; Fomsgaard, A.

    2005-01-01

    7, was identified. The HA gene showed great. sequence similarity to the highly pathogenic avian influenza A virus (HPAIV) A/Chicken/ftaly/312/97 (H5N2); however, the cleavage site sequence between HA1 and HA2 had a motif typical for low pathogenic avian influenza viruses (LPAIV). The full-length NA......During the past years increasing incidences of influenza A zoonosis have made it of uppermost importance to possess methods for rapid and precise identification and characterisation of influenza A Viruses. We present here a convenient one-step RT-PCR method that will amplify full......-length haemagglutinin (HA) and neuraminidase (NA) directly from clinical samples and from all known subtypes of influenza A. We applied the method on samples collected in September 2003 from a Danish flock of mallards with general health problems and by this a previously undescribed influenza A subtype combination, H5N...

  7. Multisegment one-step RT-PCR fluorescent labeling of influenza A virus genome for use in diagnostic microarray applications

    Microarray technology is one of the most challenging methods of influenza A virus subtyping, which is based on the antigenic properties of viral surface glycoproteins - hemagglutinin and neuraminidase. On the example of biochip for detection of influenza A/H5N1 virus we showed the possibility of using multisegment RTPCR method for amplification of fluorescently labeled cDNA of all possible influenza A virus subtypes with a single pair of primers in influenza diagnostic microarrays.

  8. Triple Combination of Oseltamivir, Amantadine, and Ribavirin Displays Synergistic Activity against Multiple Influenza Virus Strains In Vitro ▿

    Nguyen, Jack T.; Justin D Hoopes; Smee, Donald F.; Prichard, Mark N.; Driebe, Elizabeth M; Engelthaler, David M.; Le, Minh H.; Keim, Paul S; Spence, R. Paul; Went, Gregory T.

    2009-01-01

    The recurring emergence of influenza virus strains that are resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza virus pandemic. Currently, virtually all circulating strains of influenza A virus in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will add...

  9. Modeling the airborne survival of influenza virus in a residential setting: the impacts of home humidification

    Myatt Theodore A

    2010-09-01

    Full Text Available Abstract Background Laboratory research studies indicate that aerosolized influenza viruses survive for longer periods at low relative humidity (RH conditions. Further analysis has shown that absolute humidity (AH may be an improved predictor of virus survival in the environment. Maintaining airborne moisture levels that reduce survival of the virus in the air and on surfaces could be another tool for managing public health risks of influenza. Methods A multi-zone indoor air quality model was used to evaluate the ability of portable humidifiers to control moisture content of the air and the potential related benefit of decreasing survival of influenza viruses in single-family residences. We modeled indoor AH and influenza virus concentrations during winter months (Northeast US using the CONTAM multi-zone indoor air quality model. A two-story residential template was used under two different ventilation conditions - forced hot air and radiant heating. Humidity was evaluated on a room-specific and whole house basis. Estimates of emission rates for influenza virus were particle-size specific and derived from published studies and included emissions during both tidal breathing and coughing events. The survival of the influenza virus was determined based on the established relationship between AH and virus survival. Results The presence of a portable humidifier with an output of 0.16 kg water per hour in the bedroom resulted in an increase in median sleeping hours AH/RH levels of 11 to 19% compared to periods without a humidifier present. The associated percent decrease in influenza virus survival was 17.5 - 31.6%. Distribution of water vapor through a residence was estimated to yield 3 to 12% increases in AH/RH and 7.8-13.9% reductions in influenza virus survival. Conclusion This modeling analysis demonstrates the potential benefit of portable residential humidifiers in reducing the survival of aerosolized influenza virus by controlling humidity

  10. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans

    Peiris, JS Malik; Poon, Leo LM; Guan, Yi

    2016-01-01

    A recently emerged novel influenza A H1N1 virus continues to spread globally. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it likely arose through reassortment of two or more viruses of swine origin. H1N1, H1N2 and H3N2 subtype swine influenza viruses have occasionally infected humans before but such zoonotic transmission-events did not lead to sustained human-to-human transmission in the manner this swine-origin influenza virus (S-OIV) has done. Its transmission among humans appears to be higher than that observed with seasonal influenza. Children and young adults appear to those most affected and also those who appear to maintain transmission. Clinical disease generally appears mild but complications leading to hospitalization can occur, especially in those with underlying lung or cardiac disease, diabetes or those on immunosuppresive therapies. There are concerns that the virus may reassort with existing human influenza virus giving rise to more transmissible or more pathogenic viruses. The virus appears to retain the potential to transmit back to swine and thus continued reassortment with swine viruses is a cause for concern. PMID:19540800

  11. Subtype Identification of Avian Influenza Virus on DNA Microarray

    WANG Xiu-rong; YU Kang-zhen; DENG Guo-hua; SHI Rui; LIU Li-ling; QIAO Chuan-ling; BAO Hong-mei; KONG Xian-gang; CHEN Hua-lan

    2005-01-01

    We have developed a rapid microarray-based assay for the reliable detection of H5, H7 and H9 subtypes of avian influenza virus (AIV). The strains used in the experiment were A/Goose/Guangdong/1/96 (H5N1), A/African starling/983/79 (H7N1) and A/Turkey/Wiscosin/1/66 (H9N2). The capture DNAs clones which encoding approximate 500-bp avian influenza virus gene fragments obtained by RT-PCR, were spotted on a slide-bound microarray. Cy5-1abeled fluorescent cDNAs,which generated from virus RNA during reverse transcription were hybridized to these capture DNAs. These capture DNAs contained multiple fragments of the hemagglutinin and matrix protein genes of AIV respectively, for subtyping and typing AIV. The arrays were scanned to determine the probe binding sites. The hybridization pattern agreed approximately with the known grid location of each target. The results show that DNA microarray technology provides a useful diagnostic method for AIV.

  12. Susceptibility of influenza viruses circulating in Western Saudi Arabia to neuraminidase inhibitors

    Ahmed M. Tolah

    2016-04-01

    Full Text Available Objectives: To investigate the sensitivity of circulating influenza viruses in Western Saudi Arabia to neuraminidase inhibitors (NAIs; mainly, zanamivir and oseltamivir. Methods: Respiratory samples were collected from patients presenting with respiratory symptoms to King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia (KSA between September 2013 and October 2014. All samples were tested prospectively by real-time reverse-transcription polymerase chain reaction for influenza A and B viruses. Positive samples were then inoculated on Madin-Darby Canine Kidney (MDCK cells and isolated viruses were examined for their sensitivity to NAIs using fluorescent neuraminidase inhibition assay. Results: Out of 406 tested samples, 25 samples (6.2% were positive for influenza A/pdmH1N1 virus, one sample (0.25% was positive for influenza A/H3N2 virus, and 7 samples (1.7% were positive for influenza B Yamagata-like virus. Screening of isolated influenza A and B viruses (9 out of 33 for their sensitivity to NAIs showed no significant resistance to available NAIs. Conclusion: Our results show that circulating influenza viruses in Jeddah are still sensitive to NAIs.

  13. Phylogenetic analysis reveals the global migration of seasonal influenza A viruses.

    Martha I Nelson

    2007-09-01

    Full Text Available The winter seasonality of influenza A virus in temperate climates is one of the most widely recognized, yet least understood, epidemiological patterns in infectious disease. Central to understanding what drives the seasonal emergence of this important human pathogen is determining what becomes of the virus during the non-epidemic summer months. Herein, we take a step towards elucidating the seasonal emergence of influenza virus by determining the evolutionary relationship between populations of influenza A virus sampled from opposite hemispheres. We conducted a phylogenetic analysis of 487 complete genomes of human influenza A/H3N2 viruses collected between 1999 and 2005 from Australia and New Zealand in the southern hemisphere, and a representative sub-sample of viral genome sequences from 413 isolates collected in New York state, United States, representing the northern hemisphere. We show that even in areas as relatively geographically isolated as New Zealand's South Island and Western Australia, global viral migration contributes significantly to the seasonal emergence of influenza A epidemics, and that this migration has no clear directional pattern. These observations run counter to suggestions that local epidemics are triggered by the climate-driven reactivation of influenza viruses that remain latent within hosts between seasons or transmit at low efficiency between seasons. However, a complete understanding of the seasonal movements of influenza A virus will require greatly expanded global surveillance, particularly of tropical regions where the virus circulates year-round, and during non-epidemic periods in temperate climate areas.

  14. Characterization of H7 influenza A virus in wild and domestic birds in Korea.

    Hyun-Mi Kang

    Full Text Available During surveillance programs in Korea between January 2006 and March 2011, 31 H7 avian influenza viruses were isolated from wild birds and domestic ducks and genetically characterized using large-scale sequence data. All Korean H7 viruses belonged to the Eurasian lineage, which showed substantial genetic diversity, in particular in the wild birds. The Korean H7 viruses from poultry were closely related to those of wild birds. Interestingly, two viruses originating in domestic ducks in our study had the same gene constellations in all segment genes as viruses originating in wild birds. The Korean H7 isolates contained avian-type receptors (Q226 and G228, no NA stalk deletion (positions 69-73, no C-terminal deletion (positions 218-230 in NS1, and no substitutions in PB2-627, PB1-368, and M2-31, compared with H7N9 viruses. In pathogenicity experiments, none of the Korean H7 isolates tested induced clinical signs in domestic ducks or mice. Furthermore, while they replicated poorly, with low titers (10⁰·⁷⁻¹·³ EID₅₀/50 µl in domestic ducks, all five viruses replicated well (up to 7-10 dpi, 10⁰·⁷⁻⁴·³EID₅₀/50 µl in the lungs of mice, without prior adaptation. Our results suggest that domestic Korean viruses were transferred directly from wild birds through at least two independent introductions. Our data did not indicate that wild birds carried poultry viruses between Korea and China, but rather, that wild-type H7 viruses were introduced several times into different poultry populations in eastern Asia.

  15. The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian-human influenza A/Pintail/79 reassortant viruses for monkeys.

    Snyder, M H; Buckler-White, A J; London, W T; Tierney, E L; Murphy, B R

    1987-01-01

    Reassortant viruses which possessed the hemagglutinin and neuraminidase genes of wild-type human influenza A viruses and the remaining six RNA segments (internal genes) of the avian A/Pintail/Alberta/119/79 (H4N6) virus were previously found to be attenuated in humans. To study the genetic basis of this attenuation, we isolated influenza A/Pintail/79 X A/Washington/897/80 reassortant viruses which contained human influenza virus H3N2 surface glycoprotein genes and various combinations of avia...

  16. Evaluation of the Cepheid Xpert Flu Assay for rapid identification and differentiation of influenza A, influenza A 2009 H1N1, and influenza B viruses.

    Novak-Weekley, S M; Marlowe, E M; Poulter, M; Dwyer, D; Speers, D; Rawlinson, W; Baleriola, C; Robinson, C C

    2012-05-01

    The Xpert Flu Assay cartridge is a next-generation nucleic acid amplification system that provides multiplexed PCR detection of the influenza A, influenza A 2009 H1N1, and influenza B viruses in approximately 70 min with minimal hands-on time. Six laboratories participated in a clinical trial comparing the results of the new Cepheid Xpert Flu Assay to those of culture or real-time PCR with archived and prospectively collected nasal aspirate-wash (NA-W) specimens and nasopharyngeal (NP) swabs from children and adults. Discrepant results were resolved by DNA sequence analysis. After discrepant-result analysis, the sensitivities of the Xpert Flu Assay for prospective NA-W specimens containing the influenza A, influenza A 2009 H1N1, and influenza B viruses compared to those of culture were 90.0%, 100%, and 100%, respectively, while the sensitivities of the assay for prospective NP swabs compared to those of culture were 100%, 100%, and 100%, respectively. The sensitivities of the Xpert Flu Assay for archived NA-W specimens compared to those of Gen-Probe ProFlu+ PCR for the influenza A, influenza A 2009 H1N1, and influenza B viruses were 99.4%, 98.4%, and 100%, respectively, while the sensitivities of the Xpert Flu Assay for archived NP swabs compared to those of ProFlu+ were 98.1%, 100%, and 93.8%, respectively. The sensitivities of the Xpert Flu Assay with archived NP specimens compared to those of culture for the three targets were 97.5%, 100%, and 93.8%, respectively. We conclude that the Cepheid Xpert Flu Assay is an accurate and rapid method that is suitable for on-demand testing for influenza viral infection. PMID:22378908

  17. The electromigration properties of the influenza viruses

    Chalupová, Anna; Horká, Marie; Kubíček, O.; Kubíčková, Z.; Šlais, Karel

    Zagreb : Croatian Society of Chemical Engineers, 2008 - (Šegudovič, N.). s. 74 ISBN 978-953-6894-36-9. [International Symposium on Separation Science /14./. 30.09.2008-03.10.2008, Primošten] R&D Projects: GA AV ČR IAAX00310701 Institutional research plan: CEZ:AV0Z40310501 Keywords : capillary electrophoresis * virus * purification Subject RIV: CB - Analytical Chemistry, Separation

  18. Decreased influenza virus pathogenesis by infection with germicidal UV-irradiated airborne virus

    Respiratory infections are acquired by the inhalation of airborne microorganisms. To evaluate the effect of germicidal UV-irradiation on airborne contagion, infectious clouds of influenza A/PR8/34 virus were generated and exposed to known intensities of UV. Thereafter, the airborne virus was used to infect mice wherein the pathogenesis of the viral pneumonia was evaluated. Increasing doses of UV inactivated infectious airborne virus in a dose-dependent manner and reduced the mortality rates as compared to an infectious cloud of untreated virus. When a sublethal cloud of infectious virus was used, UV-irradiation modified the viral infection, as quantified by pulmonary virus titers, from a severe pneumonitis to a milder form of the disease. (author)

  19. LINGUISTIC ANALYSIS OF THE NUCLEOPROTEIN GENE OF INFLUENZA A VIRUS

    A. SKOURIKHINE; T. BURR

    2000-05-01

    We applied linguistic analysis approach, specifically N-grams, to classify nucleotide and amino acids sequences of nucleoprotein (NP) gene of the Influenza A virus isolated from a range of hosts and geographic regions. We considered letter frequency (1-grams), letter pairs frequency (2-grams) and triplets' frequency (3-grams). Classification trees based on 1,2,3-grams variables were constructed for the same NP nucleotide and amino acids strains and their classification efficiency were compared with the clustering obtained using phylogenetic analysis. The results have shown that disregarding positional information for a NP gene can provide the same level of recognition accuracy like alternative more complex classification techniques.

  20. First characterization of avian influenza viruses from Greenland 2014

    Hartby, Christina Marie; Krog, Jesper Schak; Ravn Merkel, Flemming;

    2016-01-01

    In late February 2014, unusually high numbers of wild birds, thick-billed murre (Uria lomvia), were found dead at the coast of South Greenland. To investigate the cause of death, 45 birds were submitted for laboratory examinations in Denmark. Avian influenza viruses (AIVs) with subtypes H11N2 and...... emaciated appearance of birds, suggests that the murre die-off was not due to infection with AIV, but could be the mere cause of sparse food availability or stormy weather. Here we present the first characterization of AIVs isolated in Greenland, and our results support the idea that wild birds in Greenland...

  1. In vitro inhibition of human influenza A virus replication by chloroquine

    Loh Jin

    2006-05-01

    Full Text Available Abstract Chloroquine is a 9-aminoquinolone with well-known anti-malarial effects. It has biochemical properties that could be applied to inhibit viral replication. We report here that chloroquine is able to inhibit influenza A virus replication, in vitro, and the IC50s of chloroquine against influenza A viruses H1N1 and H3N2 are lower than the plasma concentrations reached during treatment of acute malaria. The potential of chloroquine to be added to the limited range of anti-influenza drugs should be explored further, particularly since antiviral drugs play a vital role in influenza pandemic preparedness.

  2. Protection against multiple subtypes of influenza viruses by virus-like particle vaccines based on a hemagglutinin conserved epitope.

    Chen, Shaoheng; Zheng, Dan; Li, Changgui; Zhang, Wenjie; Xu, Wenting; Liu, Xueying; Fang, Fang; Chen, Ze

    2015-01-01

    We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA) trimmer, the long alpha helix (LAH), as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR) of hepatitis B virus core protein (HBc), and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP). Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB(*)) adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8) (H1N1)). In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB(*) adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections. PMID:25767809

  3. Protection against Multiple Subtypes of Influenza Viruses by Virus-Like Particle Vaccines Based on a Hemagglutinin Conserved Epitope

    Shaoheng Chen

    2015-01-01

    Full Text Available We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA trimmer, the long alpha helix (LAH, as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR of hepatitis B virus core protein (HBc, and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP. Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB* adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8 (H1N1. In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB* adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections.

  4. Hemagglutinin of influenza A virus binds specifically to cell surface nucleolin and plays a role in virus internalization.

    Chan, Che-Man; Chu, Hin; Zhang, Anna Jinxia; Leung, Lai-Han; Sze, Kong-Hung; Kao, Richard Yi-Tsun; Chik, Kenn Ka-Heng; To, Kelvin Kai-Wang; Chan, Jasper Fuk-Woo; Chen, Honglin; Jin, Dong-Yan; Liu, Liang; Yuen, Kwok-Yung

    2016-07-01

    The hemagglutinin (HA) protein of influenza A virus initiates cell entry by binding to sialic acids on target cells. In the current study, we demonstrated that in addition to sialic acids, influenza A/Puerto Rico/8/34 H1N1 (PR8) virus HA specifically binds to cell surface nucleolin (NCL). The interaction between HA and NCL was initially revealed with virus overlay protein binding assay (VOPBA) and subsequently verified with co-immunoprecipitation. Importantly, inhibiting cell surface NCL with NCL antibody, blocking PR8 viruses with purified NCL protein, or depleting endogenous NCL with siRNA all substantially reduced influenza virus internalization. We further demonstrated that NCL was a conserved cellular factor required for the entry of multiple influenza A viruses, including H1N1, H3N2, H5N1, and H7N9. Overall, our findings identified a novel role of NCL in influenza virus life cycle and established NCL as one of the host cell surface proteins for the entry of influenza A virus. PMID:27085069

  5. Protection against avian influenza H9N2 virus challenge by immunization with hemagglutinin- or neuraminidase-expressing DNA in BALB/c mice

    Avian influenza viruses of H9N2 subtype are widely spread in avian species. The viruses have recently been transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. In this study, an avian influenza H9N2 virus strain (A/Chicken/Jiangsu/7/2002), isolated in Jiangsu Province, China, was used to infect BALB/c mice for adaptation. After five lung-to-lung passages, the virus was stably proliferated in a large quantity in the murine lung and caused the deaths of mice. In addition, we explored the protection induced by H9N2 virus hemagglutinin (HA)- and neuraminidase (NA)-expressing DNAs in BALB/c mice. Female BALB/c mice aged 6-8 weeks were immunized once or twice at a 3-week interval with HA-DNA and NA-DNA by electroporation, respectively, each at a dose of 3, 10 or 30 μg. The mice were challenged with a lethal dose (40x LD5) of influenza H9N2 virus four weeks after immunization once or one week after immunization twice. The protections of DNA vaccines were evaluated by the serum antibody titers, residual lung virus titers, and survival rates of the mice. The result showed that immunization once with not less than 10 μg or twice with 3 μg HA-DNA or NA-DNA provided effective protection against homologous avian influenza H9N2 virus

  6. Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds.

    Vincent J Munster

    2007-05-01

    Full Text Available Although extensive data exist on avian influenza in wild birds in North America, limited information is available from elsewhere, including Europe. Here, molecular diagnostic tools were employed for high-throughput surveillance of migratory birds, as an alternative to classical labor-intensive methods of virus isolation in eggs. This study included 36,809 samples from 323 bird species belonging to 18 orders, of which only 25 species of three orders were positive for influenza A virus. Information on species, locations, and timing is provided for all samples tested. Seven previously unknown host species for avian influenza virus were identified: barnacle goose, bean goose, brent goose, pink-footed goose, bewick's swan, common gull, and guillemot. Dabbling ducks were more frequently infected than other ducks and Anseriformes; this distinction was probably related to bird behavior rather than population sizes. Waders did not appear to play a role in the epidemiology of avian influenza in Europe, in contrast to the Americas. The high virus prevalence in ducks in Europe in spring as compared with North America could explain the differences in virus-host ecology between these continents. Most influenza A virus subtypes were detected in ducks, but H13 and H16 subtypes were detected primarily in gulls. Viruses of subtype H6 were more promiscuous in host range than other subtypes. Temporal and spatial variation in influenza virus prevalence in wild birds was observed, with influenza A virus prevalence varying by sampling location; this is probably related to migration patterns from northeast to southwest and a higher prevalence farther north along the flyways. We discuss the ecology and epidemiology of avian influenza A virus in wild birds in relation to host ecology and compare our results with published studies. These data are useful for designing new surveillance programs and are particularly relevant due to increased interest in avian influenza in

  7. Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B.

    Pahl, H L; Baeuerle, P A

    1995-01-01

    Influenza virus infection initiates transcription of a variety of genes for cytokines such as tumor necrosis factor alpha (TNF-alpha), TNF-beta, interleukin 1 alpha, (IL-1 alpha), IL-1 beta, IL-2, IL-4, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, and gamma interferon. However, the mechanism by which virus infection elicits cytokine expression remains unknown. Six influenza virus-induced cytokine genes are targets for the inducible transcription factor NF-kappa B, a central ...

  8. Giant Magnetoresistance-based Biosensor for Detection of Influenza A Virus

    Krishna, Venkatramana D.; Wu, Kai; Perez, Andres M.; WANG, JIAN-PING

    2016-01-01

    We have developed a simple and sensitive method for the detection of influenza A virus based on giant magnetoresistance (GMR) biosensor. This assay employs monoclonal antibodies to viral nucleoprotein (NP) in combination with magnetic nanoparticles (MNPs). Presence of influenza virus allows the binding of MNPs to the GMR sensor and the binding is proportional to the concentration of virus. Binding of MNPs onto the GMR sensor causes change in the resistance of sensor, which is measured in a re...

  9. Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans

    Nachbagauer, Raffael; Choi, Angela; Izikson, Ruvim; Cox, Manon M; Palese, Peter; Krammer, Florian

    2016-01-01

    ABSTRACT Influenza remains a major global health burden. Seasonal vaccines offer protection but can be rendered less effective when the virus undergoes extensive antigenic drift. Antibodies that target the highly conserved hemagglutinin stalk can protect against drifted viruses, and vaccine constructs designed to induce such antibodies form the basis for a universal influenza virus vaccine approach. In this study, we analyzed baseline and postvaccination serum samples of children (6 to 59 mon...

  10. Melaleuca alternifolia Concentrate Inhibits in Vitro Entry of Influenza Virus into Host Cells

    Lifang Jiang; Huaiyu Gu; Danyun Fang; Maxwell John Reynolds; Yue Yin; Junmei Zhou; Gucheng Zeng; Alfred King-Yin Lam; Jun Xu; Songwei Duan; Cordia Chu; Xinghua Li

    2013-01-01

    Influenza virus causes high morbidity among the infected population annually and occasionally the spread of pandemics. Melaleuca alternifolia Concentrate (MAC) is an essential oil derived from a native Australian tea tree. Our aim was to investigate whether MAC has any in vitro inhibitory effect on influenza virus infection and what mechanism does the MAC use to fight the virus infection. In this study, the antiviral activity of MAC was examined by its inhibition of cytopathic effects. In sil...

  11. Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus

    Walsh, Kevin B.; John R Teijaro; Wilker, Peter R; Jatzek, Anna; Fremgen, Daniel M.; Das, Subash C.; Watanabe, Tokiko; Hatta, Masato; Shinya, Kyoko; Suresh, Marulasiddappa; Kawaoka, Yoshihiro; Rosen, Hugh; Oldstone, Michael B. A.

    2011-01-01

    Human pandemic H1N1 2009 influenza virus rapidly infected millions worldwide and was associated with significant mortality. Antiviral drugs that inhibit influenza virus replication are the primary therapy used to diminish disease; however, there are two significant limitations to their effective use: (i) antiviral drugs exert selective pressure on the virus, resulting in the generation of more fit viral progeny that are resistant to treatment; and (ii) antiviral drugs do not directly inhibit ...

  12. Avian-origin H3N2 canine influenza A viruses in Southern China

    Li, Shoujun; Shi, Zhihai; Jiao, Peirong; Zhang, Guihong; Zhong, Zhiwen; Tian, Wenru; Long, Li-Ping; Cai, Zhipeng; Zhu, Xingquan; Liao, Ming; Wan, Xiu-Feng

    2010-01-01

    This study reports four sporadic cases of H3N2 canine influenza in southern China, which were identified from sick dogs from May 2006 to October 2007. The evolutionary analysis showed that all eight segments of these four viruses are avian-origin and phylogenetically close to the H3N2 canine influenza viruses reported earlier in South Korea. Systematic surveillance is required to monitor the disease and evolutionary behavior of this virus in canine populations in China.

  13. The evolution of H5N1 influenza viruses in ducks in southern China

    Chen, H.; Deng, G; Li, Z.; Tian, G; Li, Y; Jiao, P.; Zhang, L.; Liu, Z.; Webster, R G; Yu, K

    2004-01-01

    The pathogenicity of avian H5N1 influenza viruses to mammals has been evolving since the mid-1980s. Here, we demonstrate that H5N1 influenza viruses, isolated from apparently healthy domestic ducks in mainland China from 1999 through 2002, were becoming progressively more pathogenic for mammals, and we present a hypothesis explaining the mechanism of this evolutionary direction. Twenty-one viruses isolated from apparently healthy ducks in southern China from 1999 through 2002 were confirmed t...

  14. Induction of a Protective Heterosubtypic Immune Response Against the Influenza Virus by using Recombinant Adenoviral Vectors Expressing Hemagglutinin of the Influenza H5 Virus.

    Shmarov, M M; Sedova, E S; Verkhovskaya, L V; Rudneva, I A; Bogacheva, E A; Barykova, Yu A; Shcherbinin, D N; Lysenko, A A; Tutykhina, I L; Logunov, D Y; Smirnov, Yu A; Naroditsky, B S; Gintsburg, A L

    2010-04-01

    Influenza viruses are characterized by a high degree of antigenic variability, which causes the annual emergence of flu epidemics and irregularly timed pandemics caused by viruses with new antigenic and biological traits. Novel approaches to vaccination can help circumvent this problem. One of these new methods incorporates genetic vaccines based on adenoviral vectors. Recombinant adenoviral vectors which contain hemagglutinin-encoding genes from avian H5N1 and H5N2 (Ad-HA5-1 and Ad-HA5-2) influenza viruses were obtained using the AdEasy Adenoviral Vector System (Stratagene). Laboratory mice received a double intranasal vaccination with Ad-HA5-1 and Ad-HA5-2. This study demonstrates that immunization with recombinant adenoviruses bearing the Н 5 influenza virus hemagglutinin gene induces a immune response which protects immunized mice from a lethal dose of the H5 influenza virus. Moreover, it also protects the host from a lethal dose of the H1 virus, which belongs to the same clade as H5, but does not confer protection from the subtype H3 influenza virus, which belongs to a different clade. PMID:22649637

  15. Genetic analysis of influenza B viruses isolated in Uganda during the 2009–2010 seasons

    Byarugaba Denis K

    2013-01-01

    Full Text Available Abstract Background Influenza B viruses can cause morbidity and mortality in humans but due to the lack of an animal reservoir are not associated with pandemics. Because of this, there is relatively limited genetic sequences available for influenza B viruses, especially from developing countries. Complete genome analysis of one influenza B virus and several gene segments of other influenza B viruses isolated from Uganda from May 2009 through December 2010 was therefore undertaken in this study. Methods Samples were collected from patients showing influenza like illness and screened for influenza A and B by PCR. Influenza B viruses were isolated on Madin-Darby Canine Kidney cells and selected isolates were subsequently sequenced and analyzed phylogenetically. Findings Of the 2,089 samples collected during the period, 292 were positive by PCR for influenza A or B; 12.3% of the PCR positives were influenza B. Thirty influenza B viruses were recovered and of these 25 that grew well consistently on subculture were subjected to further analysis. All the isolates belonged to the B/Victoria-lineage as identified by hemagglutination inhibition assay and genetic analysis except one isolate that grouped with the B-Yamagata-lineage. The Ugandan B/Victoria-lineage isolates grouped in clade 1 which was defined by the N75K, N165K and S172P substitutions in hemagglutinin (HA protein clustered together with the B/Brisbane/60/2008 vaccine strain. The Yamagata-like Ugandan strain, B/Uganda/MUWRP-053/2009, clustered with clade 3 Yamagata viruses such as B/Bangladesh/3333/2007 which is characterized by S150I and N166Y substitutions in HA. Conclusion In general there was limited variation among the Ugandan isolates but they were interestingly closer to viruses from West and North Africa than from neighboring Kenya. Our isolates closely matched the World Health Organization recommended vaccines for the seasons.

  16. Surveillance and identification of influenza A viruses in wild aquatic birds in the Crimea, Ukraine (2006-2008)

    The ecology of avian influenza (AI) viruses in wild aquatic birds of Asia is poorly understood. From March 2006 through November 2008, 20 avian influenza viruses were isolated in the Crimea region of Ukraine, with an overall virus isolation frequency of 3.3%. All the viruses were isolated from thr...

  17. Evaluation of Three Live Attenuated H2 Pandemic Influenza Vaccine Candidates in Mice and Ferrets

    Chen, Grace L.; Lamirande, Elaine W.; Cheng, Xing; Torres-Velez, Fernando; Orandle, Marlene; Jin, Hong; Kemble, George; Subbarao, Kanta

    2014-01-01

    H2 influenza viruses have not circulated in humans since 1968, and therefore a significant portion of the population would be susceptible to infection should H2 influenza viruses reemerge. H2 influenza viruses continue to circulate in avian reservoirs worldwide, and these reservoirs are a potential source from which these viruses could emerge. Three reassortant cold-adapted (ca) H2 pandemic influenza vaccine candidates with hemagglutinin (HA) and neuraminidase (NA) genes derived from the wild...

  18. A Review of the Antiviral Susceptibility of Human and Avian Influenza Viruses over the Last Decade

    Ding Yuan Oh

    2014-01-01

    Full Text Available Antivirals play an important role in the prevention and treatment of influenza infections, particularly in high-risk or severely ill patients. Two classes of influenza antivirals have been available in many countries over the last decade (2004–2013, the adamantanes and the neuraminidase inhibitors (NAIs. During this period, widespread adamantane resistance has developed in circulating influenza viruses rendering these drugs useless, resulting in the reliance on the most widely available NAI, oseltamivir. However, the emergence of oseltamivir-resistant seasonal A(H1N1 viruses in 2008 demonstrated that NAI-resistant viruses could also emerge and spread globally in a similar manner to that seen for adamantane-resistant viruses. Previously, it was believed that NAI-resistant viruses had compromised replication and/or transmission. Fortunately, in 2013, the majority of circulating human influenza viruses remain sensitive to all of the NAIs, but significant work by our laboratory and others is now underway to understand what enables NAI-resistant viruses to retain the capacity to replicate and transmit. In this review, we describe how the susceptibility of circulating human and avian influenza viruses has changed over the last ten years and describe some research studies that aim to understand how NAI-resistant human and avian influenza viruses may emerge in the future.

  19. Ultrasensitive detection of influenza viruses with a glycan-based impedimetric biosensor.

    Hushegyi, András; Pihíková, Dominika; Bertok, Tomas; Adam, Vojtech; Kizek, René; Tkac, Jan

    2016-05-15

    An ultrasensitive impedimetric glycan-based biosensor for reliable and selective detection of inactivated, but intact influenza viruses H3N2 was developed. Such glycan-based approach has a distinct advantage over antibody-based detection of influenza viruses since glycans are natural viral receptors with a possibility to selectively distinguish between potentially pathogenic influenza subtypes by the glycan-based biosensors. Build-up of the biosensor was carefully optimized with atomic force microscopy applied for visualization of the biosensor surface after binding of viruses with the topology of an individual viral particle H3N2 analyzed. The glycan biosensor could detect a glycan binding lectin with a limit of detection (LOD) of 5aM. The biosensor was finally applied for analysis of influenza viruses H3N2 with LOD of 13 viral particles in 1μl, what is the lowest LOD for analysis of influenza viral particles by the glycan-based device achieved so far. The biosensor could detect H3N2 viruses selectively with a sensitivity ratio of 30 over influenza viruses H7N7. The impedimetric biosensor presented here is the most sensitive glycan-based device for detection of influenza viruses and among the most sensitive antibody or aptamer based biosensor devices. PMID:26765527

  20. Sequence-based identification and characterization of nosocomial influenza A(H1N1)pdm09 virus infections

    Jonges, M.; Rahamat-Langendoen, J.; Meijer, A.; Niesters, H. G.; Koopmans, M.

    2012-01-01

    Background: Highly transmissible viruses such as influenza are a potential source of nosocomial infections and thereby cause increased patient morbidity and mortality. Aim: To assess whether influenza virus sequence data can be used to link nosocomial influenza transmission between individuals. Meth

  1. Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

    Li, Wenfu

    2011-04-21

    Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

  2. Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza a virus infection.

    Denisova, Oxana V; Kakkola, Laura; Feng, Lin; Stenman, Jakob; Nagaraj, Ashwini; Lampe, Johanna; Yadav, Bhagwan; Aittokallio, Tero; Kaukinen, Pasi; Ahola, Tero; Kuivanen, Suvi; Vapalahti, Olli; Kantele, Anu; Tynell, Janne; Julkunen, Ilkka; Kallio-Kokko, Hannimari; Paavilainen, Henrik; Hukkanen, Veijo; Elliott, Richard M; De Brabander, Jef K; Saelens, Xavier; Kainov, Denis E

    2012-10-12

    Influenza A viruses (IAVs) infect humans and cause significant morbidity and mortality. Different treatment options have been developed; however, these were insufficient during recent IAV outbreaks. Here, we conducted a targeted chemical screen in human nonmalignant cells to validate known and search for novel host-directed antivirals. The screen validated saliphenylhalamide (SaliPhe) and identified two novel anti-IAV agents, obatoclax and gemcitabine. Further experiments demonstrated that Mcl-1 (target of obatoclax) provides a novel host target for IAV treatment. Moreover, we showed that obatoclax and SaliPhe inhibited IAV uptake and gemcitabine suppressed viral RNA transcription and replication. These compounds possess broad spectrum antiviral activity, although their antiviral efficacies were virus-, cell type-, and species-specific. Altogether, our results suggest that phase II obatoclax, investigational SaliPhe, and FDA/EMEA-approved gemcitabine represent potent antiviral agents. PMID:22910914

  3. Influenza virus samples, international law, and global health diplomacy.

    Fidler, David P

    2008-01-01

    Indonesia's decision to withhold samples of avian influenza virus A (H5N1) from the World Health Organization for much of 2007 caused a crisis in global health. The World Health Assembly produced a resolution to try to address the crisis at its May 2007 meeting. I examine how the parties to this controversy used international law in framing and negotiating the dispute. Specifically, I analyze Indonesia's use of the international legal principle of sovereignty and its appeal to rules on the protection of biological and genetic resources found in the Convention on Biological Diversity. In addition, I consider how the International Health Regulations 2005 applied to the controversy. The incident involving Indonesia's actions with virus samples illustrates both the importance and the limitations of international law in global health diplomacy. PMID:18258086

  4. Antibodies to H5 subtype avian influenza virus and Japanese encephalitis virus in northern pintails (Anas acuta) sampled in Japan

    Blood samples from 105 northern pintails (Anas acuta) captured on Hokkaido, Japan were tested for antibodies to avian influenza virus (AIV), Japanese encephalitis virus (JEV) and West Nile virus (WNV) to assess possible involvement of this species in the transmission and spread of economically impor...

  5. VIRUS VACCINE RESEARCH AT THE NATIONAL ANIMAL DISEASE CENTER: LESSONS FROM SWINE INFLUENZA VIRUS AND BOVINE VIRAL DIARRHEA VIRUS

    The continuing emergence of novel subtypes and genetic variants of swine influenza viruses (SIV) causing swine flu challenges our ability to effectively manage this high morbidity disease among swine. New strategic approaches for vaccine development must be considered to keep up with the ever-evolv...

  6. Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - implications for cross-reactivity of neutralizing antibodies

    Jing eSun; Ulrich eKudahl; Zhiwei eCao; Christian eSimon; Reinherz, Ellis L; Vladimir eBrusic

    2014-01-01

    Influenza viruses continue to cause substantial morbidity and mortality worldwide. Fast gene mutation on surface proteins of influenza virus result in increasing resistance to current vaccines and available antiviral drugs. Broadly neutralizing antibodies represent targets for prophylactic and therapeutic treatments of influenza. We performed a systematic bioinformatics study of cross-reactivity of neutralizing antibodies against influenza virus surface glycoprotein hemagglutinin (HA). This s...

  7. The Analysis of B-Cell Epitopes of Influenza Virus Hemagglutinin.

    Shcherbinin, D N; Alekseeva, S V; Shmarov, M M; Smirnov, Yu A; Naroditskiy, B S; Gintsburg, A L

    2016-01-01

    Vaccination has been successfully used to prevent influenza for a long time. Influenza virus hemagglutinin (HA), which induces a humoral immune response in humans and protection against the flu, is the main antigenic component of modern influenza vaccines. However, new seasonal and pandemic influenza virus variants with altered structures of HA occasionally occur. This allows the pathogen to avoid neutralization with antibodies produced in response to previous vaccination. Development of a vaccine with the new variants of HA acting as antigens takes a long time. Therefore, during an epidemic, it is important to have passive immunization agents to prevent and treat influenza, which can be monoclonal or single-domain antibodies with universal specificity (broad-spectrum agents). We considered antibodies to conserved epitopes of influenza virus antigens as universal ones. In this paper, we tried to characterize the main B-cell epitopes of hemagglutinin and analyze our own and literature data on broadly neutralizing antibodies. We conducted a computer analysis of the best known conformational epitopes of influenza virus HAs using materials of different databases. The analysis showed that the core of the HA molecule, whose antibodies demonstrate pronounced heterosubtypic activity, can be used as a target for the search for and development of broad-spectrum antibodies to the influenza virus. PMID:27099781

  8. Vaccine-Induced Boosting of Influenza Virus-Specific CD4 T Cells in Younger and Aged Humans

    Dolfi, Douglas V.; Mansfield, Kathleen D.; Kurupati, Raj K.; Kannan, Senthil; Doyle, Susan A.; Ertl, Hildegund C. J.; Schmader, Kenneth E.; Wherry, E. John

    2013-01-01

    Current yearly influenza virus vaccines induce strain-specific neutralizing antibody (NAb) responses providing protective immunity to closely matched viruses. However, these vaccines are often poorly effective in high-risk groups such as the elderly and challenges exist in predicting yearly or emerging pandemic influenza virus strains to include in the vaccines. Thus, there has been considerable emphasis on understanding broadly protective immunological mechanisms for influenza virus. Recent ...

  9. Are ducks contributing to the endemicity of highly pathogenic H5N1 influenza virus in Asia?

    Sturm-Ramirez, K. M.; Hulse-Post, D. J.; Govorkova, E A; Humberd, J.; Seiler, P.; Puthavathana, P.; Buranathai, C; Nguyen, T. D.; Chaisingh, A.; Long, H. T.; Naipospos, T. S. P.; Chen, H.; Ellis, T M; Guan, Y.; Peiris, J. S. M.

    2005-01-01

    Wild waterfowl are the natural reservoir of all influenza A viruses, and these viruses are usually nonpathogenic in these birds. However, since late 2002, H5N1 outbreaks in Asia have resulted in mortality among waterfowl in recreational parks, domestic flocks, and wild migratory birds. The evolutionary stasis between influenza virus and its natural host may have been disrupted, prompting us to ask whether waterfowl are resistant to H5N1 influenza virus disease and whether they can still act a...

  10. Effect of influenza A/equine/H3N8 virus isolate variation on the measurement of equine antibody responses.

    Bogdan, J R; Morley, P S; Townsend, H G; Haines, D M

    1993-01-01

    This study has tested the effect of using homologous or heterologous equine influenza A virus isolates to evaluate serum antibody levels to influenza A virus in vaccinated and naturally-infected horses. In addition, the potential effect of antigenic selection of virus variants in egg versus tissue culture propagation systems was studied. Serum antibody levels in samples from horses recently infected with a local influenza A virus isolate (A/equine 2/Saskatoon/1/90) or recently vaccinated with...

  11. The Irrationality of GOF Avian Influenza Virus Research.

    Wain-Hobson, Simon

    2014-01-01

    The last two and a half years have witnessed a curious debate in virology characterized by a remarkable lack of discussion. It goes by the misleading epithet "gain of function" (GOF) influenza virus research, or simply GOF. As will be seen, there is nothing good to be gained. The controversial experiments confer aerosol transmission on avian influenza virus strains that can infect humans, but which are not naturally transmitted between humans. Some of the newer strains are clearly highly pathogenic for man. It will be shown here that the benefits of the work are erroneous and overstated while the risk of an accident is finite, if small. The consequence of any accident would be anywhere from a handful of infections to a catastrophic pandemic. There has been a single open international meeting in this period, which is surprising given that openness and discussion are essential to good science. Despite US and EU government funding, no risk-benefit analysis has been published, which again is surprising. This research can be duplicated readily in many labs and requires little high tech. It falls under the definition of DURC without the slightest shadow of a doubt and constitutes the most important challenge facing contemporary biology. PMID:25077136

  12. Influenza virus mRNA trafficking through host nuclear speckles.

    Mor, Amir; White, Alexander; Zhang, Ke; Thompson, Matthew; Esparza, Matthew; Muñoz-Moreno, Raquel; Koide, Kazunori; Lynch, Kristen W; García-Sastre, Adolfo; Fontoura, Beatriz M A

    2016-01-01

    Influenza A virus is a human pathogen with a genome composed of eight viral RNA segments that replicate in the nucleus. Two viral mRNAs are alternatively spliced. The unspliced M1 mRNA is translated into the matrix M1 protein, while the ion channel M2 protein is generated after alternative splicing. These proteins are critical mediators of viral trafficking and budding. We show that the influenza virus uses nuclear speckles to promote post-transcriptional splicing of its M1 mRNA. We assign previously unknown roles for the viral NS1 protein and cellular factors to an intranuclear trafficking pathway that targets the viral M1 mRNA to nuclear speckles, mediates splicing at these nuclear bodies and exports the spliced M2 mRNA from the nucleus. Given that nuclear speckles are storage sites for splicing factors, which leave these sites to splice cellular pre-mRNAs at transcribing genes, we reveal a functional subversion of nuclear speckles to promote viral gene expression. PMID:27572970

  13. [Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

    Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

    2009-01-01

    The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic. PMID:19240010

  14. Persistent Infection of Drug-resistant Influenza A Virus during Chemotherapy for Malignant Lymphoma.

    Kawakami, Toru; Hirabayashi, Yukio; Kawakami, Fumihiro; Isobe, Rei; Kaneko, Naoto; Mimura, Yuto; Ito, Toshiro; Furuta, Kiyoshi; Shimazaki, Mami; Nakazawa, Hideyuki; Kitano, Kiyoshi

    2016-01-01

    We herein report the case of an 80-year-old man with malignant lymphoma who became persistently infected with influenza A virus. Although he was repeatedly treated with NA inhibitors, such as oseltamivir or peramivir, nasal cavity swab tests for influenza A antigen continued to be positive for more than 2 months. Virological analyses revealed that he was infected with the NA inhibitor-resistant A (H3N2) virus possessing an R292K substitution in the NA protein. These findings suggest that a drug-resistant influenza virus strain might selectively survive antiviral therapy in elderly patients with refractory malignant lymphoma undergoing multiple chemotherapies. PMID:27374689

  15. Experience in applying 60Co γ-rays for careful production of inactivated influenza virus vaccines

    Radiation doses between 12 and 13 kGy at 15-20 0C were sufficient for mild inactivation of influenza viruses. Under these conditions the decisive surface antigens hemagglutinin and neuraminidase were treated with care, and the preparations of influenza viruses revealed good immunogenicity in the animal experiment. Morphologic alterations after application of 20 kGy could not be demonstrated in electron microscopic investigations. Doses of 9.5-9.9 kGy in combination with a very low quantity of HCHO (1:15000) is sufficient for inactivation. Reactivation of influenza viruses after treatment could not be demonstrated. (author)

  16. Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation

    Pengxiang Chang; Kuchipudi, Suresh V; Kenneth H. Mellits; Sujith Sebastian; Joe James; Jinhua Liu; Holly Shelton; Kin-Chow Chang

    2015-01-01

    Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) in...

  17. Clinical and epidemiological evaluation of a live, cold-adapted influenza vaccine for 3-14-year-olds.

    Rudenko, L. G.; Lonskaya, N. I.; Klimov, A. I.; Vasilieva, R. I.; Ramirez, A.

    1996-01-01

    Reported is a study of live, cold-adapted (CA) reassortant mono-, di-, and trivalent influenza type A and B vaccines in a series of controlled clinical and epidemiological investigations involving nearly 130 000 children aged 3-15 years. The results of clinical, immunological, and morbidity investigations of the vaccinees and a control group over 6-months' follow-up indicated that the vaccines were completely attenuated by the children. Transient febrile reactions occurred in < 1% of the children after vaccination, including double seronegative individuals with low antibody titres. The type A reisolates examined were genetically stable. The reassortants did not suppress each other after simultaneous inoculation of children and stimulated antibody response to influenza virus strains A1, A3, and B. The incidence of influenza-like diseases was approximately 30-40% lower among the vaccinated group than among the control group. The study demonstrates, for the first time, the efficacy of CA vaccine against infections caused by influenza B virus. PMID:8653819

  18. New avian influenza A virus subtype combination H5N7 identified in Danish mallard ducks

    Bragstad, K.; Jørgensen, Poul Henrik; Handberg, Kurt;

    2005-01-01

    During the past years increasing incidences of influenza A zoonosis have made it of uppermost importance to possess methods for rapid and precise identification and characterisation of influenza A Viruses. We present here a convenient one-step RT-PCR method that will amplify full-length haemagglu......During the past years increasing incidences of influenza A zoonosis have made it of uppermost importance to possess methods for rapid and precise identification and characterisation of influenza A Viruses. We present here a convenient one-step RT-PCR method that will amplify full......-length haemagglutinin (HA) and neuraminidase (NA) directly from clinical samples and from all known subtypes of influenza A. We applied the method on samples collected in September 2003 from a Danish flock of mallards with general health problems and by this a previously undescribed influenza A subtype combination, H5N...

  19. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    Jiang, Zhiwu; Gu, Liming; Chen, Yanxia

    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. PMID:27525278

  20. Inhibition of influenza A virus (H1N1 fusion by benzenesulfonamide derivatives targeting viral hemagglutinin.

    Lei Zhu

    Full Text Available Hemagglutinin (HA of the influenza virus plays a crucial role in the early stage of the viral life cycle by binding to sialic acid on the surface of host epithelial cells and mediating fusion between virus envelope and endosome membrane for the release of viral genomes into the cytoplasm. To initiate virus fusion, endosome pH is lowered by acidification causing an irreversible conformational change of HA, which in turn results in a fusogenic HA. In this study, we describe characterization of an HA inhibitor of influenza H1N1 viruses, RO5464466. One-cycle time course study in MDCK cells showed that this compound acted at an early step of influenza virus replication. Results from HA-mediated hemolysis of chicken red blood cells and trypsin sensitivity assay of isolated HA clearly showed that RO5464466 targeted HA. In cell-based assays involving multiple rounds of virus infection and replication, RO5464466 inhibited an established influenza infection. The overall production of progeny viruses, as a result of the compound's inhibitory effect on fusion, was dramatically reduced by 8 log units when compared with a negative control. Furthermore, RO5487624, a close analogue of RO5464466, with pharmacokinetic properties suitable for in vivo efficacy studies displayed a protective effect on mice that were lethally challenged with influenza H1N1 virus. These results might benefit further characterization and development of novel anti-influenza agents by targeting viral hemagglutinin.

  1. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    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.

  2. Evaluation of the Cepheid Xpert Flu Assay for Rapid Identification and Differentiation of Influenza A, Influenza A 2009 H1N1, and Influenza B Viruses

    Novak-Weekley, S. M.; Marlowe, E. M.; Poulter, M.; Dwyer, D.; Speers, D; Rawlinson, W; Baleriola, C.; Robinson, C C

    2012-01-01

    The Xpert Flu Assay cartridge is a next-generation nucleic acid amplification system that provides multiplexed PCR detection of the influenza A, influenza A 2009 H1N1, and influenza B viruses in approximately 70 min with minimal hands-on time. Six laboratories participated in a clinical trial comparing the results of the new Cepheid Xpert Flu Assay to those of culture or real-time PCR with archived and prospectively collected nasal aspirate-wash (NA-W) specimens and nasopharyngeal (NP) swabs ...

  3. Severity of pneumonia due to new H1N1 influenza virus in ferrets is intermediate between that due to seasonal H1N1 virus and highly pathogenic avian influenza H5N1 virus

    Brand, Judith; Stittelaar, Koert; Amerongen, Geert van; Rimmelzwaan, Guus; Simon, James; de Wit, Emmie; Munster, Vincent; Bestebroer, Theo; Fouchier, Ron; Kuiken, Thijs; Osterhaus, Ab

    2010-01-01

    textabstractBackground. The newly emerged influenza A(H1N1) virus (new H1N1 virus) is causing the first influenza pandemic of this century. Three influenza pandemics of the previous century caused variable mortality, which largely depended on the development of severe pneumonia. However, the ability of the new H1N1 virus to cause pneumonia is poorly understood. Methods. The new H1N1 virus was inoculated intratracheally into ferrets. Its ability to cause pneumonia was compared with that of sea...

  4. Toward a Method for Tracking Virus Evolutionary Trajectory Applied to the Pandemic H1N1 2009 Influenza Virus

    Squires, R Burke; Pickett, Brett E.; Das, Sajal; Scheuermann, Richard H

    2014-01-01

    In 2009 a novel pandemic H1N1 influenza virus (H1N1pdm09) emerged as the first official influenza pandemic of the 21st century. Early genomic sequence analysis pointed to the swine origin of the virus. Here we report a novel computational approach to determine the evolutionary trajectory of viral sequences that uses data-driven estimations of nucleotide substitution rates to track the gradual accumulation of observed sequence alterations over time. Phylogenetic analysis and multiple sequence ...

  5. Pandemic influenza A (H1N1) virus in households with young children

    Peltola, Ville; Teros‐Jaakkola, Tamara; Rulli, Maris; Toivonen, Laura; Broberg, Eeva; Waris, Matti; Mertsola, Jussi

    2011-01-01

    Please cite this paper as: Peltola et al. (2011) Pandemic influenza A (H1N1) virus in households with young children. Influenza and Other Respiratory Viruses 6(3), e21–e24. Abstract Background  Influenza viruses may cause a severe infection in infants and young children. The transmission patterns of pandemic 2009 influenza A (H1N1) within households with young children are poorly characterized. Methods  Household members of six children younger than 1·5 years with documented 2009 influenza A (H1N1) infection were studied by daily symptom diaries and serial parent‐collected nasal swab samples for detection of influenza A by reverse transcription polymerase chain reaction (RT‐PCR) assay. Results  Laboratory‐confirmed, symptomatic influenza was documented in 11 of 15 household contacts of young children with pandemic influenza (73%; 95% CI, 48–99). In five contact cases symptoms started earlier, in three cases on the same day, and in three cases after the onset of symptoms in the youngest child. The first case with influenza A (H1N1) within the household was an elder sibling in two households, father in two households, the youngest child in one household, and the youngest child at the same time with a sibling in one household. The median copy number of influenza virus was higher in children than in adults (4·2 × 107 versus 4·9 × 104, P = 0·02). Conclusions  This study demonstrates the feasibility of nasal swab sampling by parents in investigation of household transmission of influenza. The results support influenza vaccination of all household contacts of young children. PMID:21951638

  6. Predictors of indoor absolute humidity and estimated effects on influenza virus survival in grade schools

    Koep Tyler H; Enders Felicity T; Pierret Chris; Ekker Stephen C; Krageschmidt Dale; Neff Kevin L; Lipsitch Marc; Shaman Jeffrey; Huskins W Charles

    2013-01-01

    Abstract Background Low absolute humidity (AH) has been associated with increased influenza virus survival and transmissibility and the onset of seasonal influenza outbreaks. Humidification of indoor environments may mitigate viral transmission and may be an important control strategy, particularly in schools where viral transmission is common and contributes to the spread of influenza in communities. However, the variability and predictors of AH in the indoor school environment and the feasi...

  7. Pyrrolidinobenzoic Acid Inhibitors of Influenza Virus Neuraminidase: the Hydrophobic Side Chain Influences Type A Subtype Selectivity

    Li, Yanwu; Silamkoti, Arundutt; Kolavi, Gundurao; Mou, Liyuan; Gulati, Shelly; Air, Gillian M; Brouillette, Wayne J.

    2012-01-01

    Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that ...

  8. A Complete Molecular Diagnostic Procedure for Applications in Surveillance and Subtyping of Avian Influenza Virus

    Chun-Hsien Tseng; Hsiang-Jung Tsai; Chung-Ming Chang

    2014-01-01

    Introduction. The following complete molecular diagnostic procedure we developed, based on real-time quantitative PCR and traditional PCR, is effective for avian influenza surveillance, virus subtyping, and viral genome sequencing. Method. This study provides a specific and sensitive step-by-step procedure for efficient avian influenza identification of 16 hemagglutinin and 9 neuraminidase avian influenza subtypes. Result and Conclusion. This diagnostic procedure may prove exceedingly useful ...

  9. CD206+ Cell Number Differentiates Influenza A (H1N1pdm09 from Seasonal Influenza A Virus in Fatal Cases

    Heidi G. Rodriguez-Ramirez

    2014-01-01

    Full Text Available In 2009, a new influenza A (H1N1 virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1pdm09. Cytokines (inflammatory and anti-inflammatory and cellular markers (macrophages and lymphocytes subpopulation markers were analyzed in lung tissue from both influenza A (H1N1pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1pdm09 and seasonal cases when compared with healthy lung tissue (P<0.05. Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1pdm09 and seasonal influenza virus (P<0.05. Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung were found in influenza A (H1N1pdm09 when compared with seasonal influenza virus (P<0.05, and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1pdm09 (P<0.05. In conclusion, CD206+ cells differentiate between influenza A (H1N1pdm09 and seasonal influenza virus in lung tissue of fatal cases.

  10. Bacterially produced recombinant influenza vaccines based on virus-like particles.

    Andrea Jegerlehner

    Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.

  11. Isolation of H15N7 influenza virus from wild birds in Eastern Europe and its relationship to viruses from other regions

    Background: Continuous monitoring of influenza viruses circulating in the natural reservoir in wild birds is important for early warning and forecasting of epizootic and epidemiological situation with influenza. These studies allow getting much valuable information on the environmental features of ...

  12. A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

    Ryuta Ueda

    Full Text Available BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA, a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1 the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins than the membranes of cells in S/G2/M-phase; 2 the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3 S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

  13. Amantadine resistance among highly pathogenic avian influenza viruses (H5N1) isolated from India.

    Jacob, Aron; Sood, Richa; Chanu, Kh Victoria; Bhatia, Sandeep; Khandia, Rekha; Pateriya, A K; Nagarajan, S; Dimri, U; Kulkarni, D D

    2016-02-01

    Emergence of antiviral resistance among H5N1 avian influenza viruses is the major challenge in the control of pandemic influenza. Matrix 2 (M2) inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) are the two classes of antiviral agents that are specifically active against influenza viruses and are used for both treatment and prophylaxis of influenza infections. Amantadine targets the M2 ion channel of influenza A virus and interrupts virus life cycle through blockade of hydrogen ion influx. This prevents uncoating of the virus in infected host cells which impedes the release of ribonucleoprotein required for transcription and replication of virion in the nucleus. The present study was carried out to review the status of amantadine resistance in H5N1 viruses isolated from India and to study their replicative capability. Results of the study revealed resistance to amantadine in antiviral assay among four H5N1 viruses out of which two viruses had Serine 31 Asparagine (AGT-AAT i.e., S31N) mutation and two had Valine 27 Alanine (GTT-GCT i.e., V27A) mutation. The four resistant viruses not only exhibited significant difference in effective concentration 50% (EC50) values of amantadine hydrochloride from that of susceptible viruses (P < 0.0001) but also showed significant difference between two different types (S31N and V27A) of mutant viruses (P < 0.05). Resistance to amantadine could also be demonstrated in a simple HA test after replication of the viruses in MDCK cells in presence of amantadine. The study identifies the correlation between in vitro antiviral assay and presence of established molecular markers of resistance, the retention of replicative capacity in the presence of amantadine hydrochloride by the resistant viruses and the emergence of resistant mutations against amantadine among avian influenza viruses (H5N1) without selective drug pressure. PMID:26639679

  14. Homo- and Heterosubtypic Low Pathogenic Avian Influenza Exposure on H5N1 Highly Pathogenic Avian Influenza Virus Infection in Wood Ducks (Aix sponsa)

    Costa, Taiana P.; Brown, Justin D.; Howerth, Elizabeth W.; Stallknecht, David E.; Swayne, David E.

    2011-01-01

    Wild birds in the Orders Anseriformes and Charadriiformes are the natural reservoirs for avian influenza (AI) viruses. Although they are often infected with multiple AI viruses, the significance and extent of acquired immunity in these populations is not understood. Pre-existing immunity to AI virus has been shown to modulate the outcome of a highly pathogenic avian influenza (HPAI) virus infection in multiple domestic avian species, but few studies have addressed this effect in wild birds. I...

  15. Host shifts and molecular evolution of H7 avian influenza virus hemagglutinin

    Stallknecht David E

    2011-06-01

    Full Text Available Abstract Evolutionary consequences of host shifts represent a challenge to identify the mechanisms involved in the emergence of influenza A (IA viruses. In this study we focused on the evolutionary history of H7 IA virus in wild and domestic birds, with a particular emphasis on host shifts consequences on the molecular evolution of the hemagglutinin (HA gene. Based on a dataset of 414 HA nucleotide sequences, we performed an extensive phylogeographic analysis in order to identify the overall genetic structure of H7 IA viruses. We then identified host shift events and investigated viral population dynamics in wild and domestic birds, independently. Finally, we estimated changes in nucleotide substitution rates and tested for positive selection in the HA gene. A strong association between the geographic origin and the genetic structure was observed, with four main clades including viruses isolated in North America, South America, Australia and Eurasia-Africa. We identified ten potential events of virus introduction from wild to domestic birds, but little evidence for spillover of viruses from poultry to wild waterbirds. Several sites involved in host specificity (addition of a glycosylation site in the receptor binding domain and virulence (insertion of amino acids in the cleavage site were found to be positively selected in HA nucleotide sequences, in genetically unrelated lineages, suggesting parallel evolution for the HA gene of IA viruses in domestic birds. These results highlight that evolutionary consequences of bird host shifts would need to be further studied to understand the ecological and molecular mechanisms involved in the emergence of domestic bird-adapted viruses.

  16. The pathogenesis of low pathogenicity H7 avian influenza viruses in chickens, ducks and turkeys

    Pope Conrad R

    2010-11-01

    Full Text Available Abstract Background Avian influenza (AI viruses infect numerous avian species, and low pathogenicity (LP AI viruses of the H7 subtype are typically reported to produce mild or subclinical infections in both wild aquatic birds and domestic poultry. However relatively little work has been done to compare LPAI viruses from different avian species for their ability to cause disease in domestic poultry under the same conditions. In this study twelve H7 LPAI virus isolates from North America were each evaluated for their comparative pathogenesis in chickens, ducks, and turkeys. Results All 12 isolates were able to infect all three species at a dose of 106 50% egg infectious doses based on seroconversion, although not all animals seroconverted with each isolate-species combination. The severity of disease varied among isolate and species combinations, but there was a consistent trend for clinical disease to be most severe in turkeys where all 12 isolates induced disease, and mortality was observed in turkeys exposed to 9 of the 12 viruses. Turkeys also shed virus by the oral and cloacal routes at significantly higher titers than either ducks or chickens at numerous time points. Only 3 isolates induced observable clinical disease in ducks and only 6 isolates induced disease in chickens, which was generally very mild and did not result in mortality. Full genome sequence was completed for all 12 isolates and some isolates did have features consistent with adaptation to poultry (e.g. NA stalk deletions, however none of these features correlated with disease severity. Conclusions The data suggests that turkeys may be more susceptible to clinical disease from the H7 LPAI viruses included in this study than either chickens or ducks. However the severity of disease and degree of virus shed was not clearly correlated with any isolate or group of isolates, but relied on specific species and isolate combinations.

  17. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses

  18. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    Pan, Yang [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Sasaki, Tadahiro [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Inoue, Yuji [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yasugi, Mayo [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Du, Anariwa [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Boonsathorn, Naphatsawan [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Ibrahim, Madiha S. [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour (Egypt); and others

    2014-07-18

    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

  19. Direct Administration in the Respiratory Tract Improves Efficacy of Broadly Neutralizing Anti-Influenza Virus Monoclonal Antibodies

    Leyva-Grado, Victor H.; Tan, Gene S.; Leon, Paul E.; Yondola, Mark; Palese, Peter

    2015-01-01

    The emergence of influenza virus strains resistant to approved neuraminidase inhibitors and the time constrains after infection when these drugs can be effective constitute major drawbacks for this class of drugs. This highlights a critical need to discover new therapeutic agents that can be used for the treatment of influenza virus-infected patients. The use of broadly neutralizing anti-influenza monoclonal antibodies (MAbs) has been sought as an alternative immunotherapy against influenza i...

  20. Antigenic and genetic evolution of equine influenza a (H3N8) virus from 1968 to 2007

    Lewis, N. S.; Daly, J M; Russell, C.A.; Horton, D. L.; Skepner, E.; Bryant, N. A.; Burke, D. F.; Rash, A.S.; Wood, J.L.N.; Chambers, T M; Fouchier, R. A. M.; Mumford, J. A.; Elton, D.M.; Smith, D J

    2011-01-01

    textabstractEquine influenza virus is a major respiratory pathogen in horses, and outbreaks of disease often lead to substantial disruption to and economic losses for equestrian industries. The hemagglutinin (HA) protein is of key importance in the control of equine influenza because HA is the primary target of the protective immune response and the main component of currently licensed influenza vaccines. However, the influenza virus HA protein changes over time, a process called antigenic dr...

  1. Inactivation of avian influenza virus in chicken litter as a potential method to decontaminate poultry houses

    Full cleaning and disinfection of a poultry house after an avian influenza virus (AIV) outbreak is expensive and labor intensive. An alternative to full house cleaning and disinfection is to inactivate the virus with high temperatures within the house. Litter in the house normally has a high virus...

  2. Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China

    Ma, Qing-Xia; Jiang, Wen-Ming; Liu, Shuo; Wang, Su-Chun; Zhuang, Qing-Ye; Hou, Guang-Yu; Liu, Xiang-Ming; Sui, Zheng-Hong; Chen, Ji-Ming

    2014-01-01

    Subclinical infection of vaccinated chickens with a highly pathogenic avian influenza A(H5N2) virus was identified through routine surveillance in China. Investigation suggested that the virus has evolved into multiple genotypes. To better control transmission of the virus, we recommend a strengthened program of education, biosecurity, rapid diagnostics, surveillance, and elimination of infected poultry.

  3. Influenza A and B viruses in the population of Vojvodina, Serbia

    Radovanov J.

    2014-01-01

    Full Text Available At present, two influenza A viruses, H1N1pdm09 and H3N2, along with influenza B virus co-circulate in the human population, causing endemic and seasonal epidemic acute febrile respiratory infections, sometimes with life-threatening complications. Detection of influenza viruses in nasopharyngeal swab samples was done by real-time RT-PCR. There were 60.2% (53/88 positive samples in 2010/11, 63.4% (52/82 in 2011/12, and 49.9% (184/369 in 2012/13. Among the positive patients, influenza A viruses were predominant during the first two seasons, while influenza B type was more active during 2012/13. Subtyping of influenza A positive samples revealed the presence of A (H1N1pdm09 in 2010/11, A (H3N2 in 2011/12, while in 2012/13, both subtypes were detected. The highest seroprevalence against influenza A was in the age-group 30-64, and against influenza B in adults aged 30-64 and >65. [Projekat Ministarstva nauke Republike Srbije, br. TR31084

  4. Risk Perceptions for Avian Influenza Virus Infection among Poultry Workers, China

    Yu, Qi; Liu, Linqing; Pu, Juan; Zhao, Jingyi; Sun, Yipeng; Shen, Guangnian; Wei, Haitao; Zhu, Junjie; Zheng, Ruifeng; Xiong, Dongyan; Liu, Xiaodong; Liu, Jinhua

    2013-01-01

    To determine risk for avian influenza virus infection, we conducted serologic surveillance for H5 and H9 subtypes among poultry workers in Beijing, China, 2009–2010, and assessed workers’ understanding of avian influenza. We found that poultry workers had considerable risk for infection with H9 subtypes. Increasing their knowledge could prevent future infections.

  5. Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine

    In the U.S., despite available swine influenza virus (SIV) vaccines, multiple influenza subtypes as well as antigenic and genetic variants within subtypes continue to circulate in the swine population. One of the challenges to control and eliminate SIV is that the currently used inactivated influenz...

  6. Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses

    Makino Akiko

    2011-03-01

    Full Text Available Abstract Since the beginning of the 20th century, humans have experienced four influenza pandemics, including the devastating 1918 'Spanish influenza'. Moreover, H5N1 highly pathogenic avian influenza (HPAI viruses are currently spreading worldwide, although they are not yet efficiently transmitted among humans. While the threat of a global pandemic involving a highly pathogenic influenza virus strain looms large, our mechanisms to address such a catastrophe remain limited. Here, we show that pre-stimulation of Toll-like receptors (TLRs 2 and 4 increased resistance against influenza viruses known to induce high pathogenicity in animal models. Our data emphasize the complexity of the host response against different influenza viruses, and suggest that TLR agonists might be utilized to protect against lethality associated with highly pathogenic influenza virus infection in humans.

  7. Virus-like particle vaccine protects against H3N2 canine influenza virus in dog

    Lee, Dong-Hun; Bae, Sang-Woo; Park, Jae-Keun; Kwon, Jung-Hoon; Yuk, Seong-Su; Song, Jae-Min; Kang, Sang-Moo; Kwon, Yong-Kuk; Kim, Hwi-Yool; Song, Chang-Seon

    2013-01-01

    In the present study, virus-like particles (VLPs) were evaluated as a candidate veterinary vaccine against canine influenza virus (CIV) subtype H3N2. Specific pathogen-free (SPF) beagle dogs received a single injection of a VLP vaccine containing hemagglutinin (HA) and M1 protein of CIV H3N2 (H3 HA VLP). The vaccine was tested at 3 different doses with an adjuvant and 1 dose without an adjuvant. To evaluate the immunogenicity and protective efficacy of the H3 HA VLP vaccine, we performed hema...

  8. Genetic and antigenic characterization of influenza A virus circulating in Danish swine during the past decade

    Fobian, Kristina; Kirk, Isa Kristina; Breum, Solvej Østergaard;

    complex epidemiology of circulating swine influenza virus in Denmark and indicates that vaccine development targeted against Danish H1N1 and H1N2 need only to include few components for the induction of cross protection against the predominant strains. The study was supported by grants from “European......Influenza A virus has been endemic in Danish swine for the last 30 years, with H1N1 and H1N2 being the dominating subtypes. The purpose of this study was to investigate the genetic and antigenic evolution of the influenza viruses found in Danish swine during the last 10 years. A total of 78 samples...... were isolated in MDCK cells, RNA extracted and the hemagglutinin and neuraminidase genes full length sequenced. In addition, the isolates were tested in hemagglutination inhibition (HI) tests against a panel of known antisera raised against a range of European swine influenza virus isolates...

  9. The challenges of avian influenza virus:mechanism,epidemiology and control

    George; F.GAO; Pang-Chui; SHAW

    2009-01-01

    Early 2009, eight human infection cases of H5N1 highly pathogenic avian influenza (HPAI) virus, with 5 death cases, were reported in China. This again made the world alert on a possible pandemic worldwide, probably caused by

  10. Synthesis and Anti-influenza Virus Activity of Ethyl 6-Bromo-5-hydroxyindole-3-carboxylate Derivatives

    Yan Fang ZHAO; Jin Hua DONG; Ping GONG

    2004-01-01

    A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.

  11. Post-exposure treatment with whole inactivated H5N1 avian influenza virus protects against lethal homologous virus infection in mice

    Hagan, Mable; Ranadheera, Charlene; Audet, Jonathan; Morin, Jocelyn; Leung, Anders; Kobasa, Darwyn

    2016-01-01

    Concerns with H5N1 influenza viruses include their prevalence in wild and domestic poultry, high mortality rate (~60%) in humans with some strains, lack of pre-existing immunity in humans, and the possibility that these viruses acquire mutations that enable efficient transmission between humans. H5 subtype viruses of Eurasian origin have recently appeared in wild and domestic bird populations in North America, and have led to the generation of new virus strains that are highly pathogenic in poultry. These new H5 HA containing viruses with their ability to evolve rapidly represent an unknown threat to humans in contact with infected poultry, and vaccination with an off-the-shelf vaccine may be impractical to provide protection to at-risk individuals. Instead, we have evaluated the efficacy of a formalin-inactivated vaccine, which could be derived directly from a circulating virus, to provide post-exposure protection. This strategy was evaluated using a prototypic highly pathogenic avian H5N1 strain, A/Vietnam/1203/2004, and demonstrated rapid induction of adaptive immune responses providing protection in a mammalian model of lethal infection. Additionally, this post-exposure vaccine was highly efficacious when administered 24 hours after exposure. This study offers a platform for developing effective post-exposure vaccines for treatment of highly virulent influenza infections. PMID:27405487

  12. Post-exposure treatment with whole inactivated H5N1 avian influenza virus protects against lethal homologous virus infection in mice.

    Hagan, Mable; Ranadheera, Charlene; Audet, Jonathan; Morin, Jocelyn; Leung, Anders; Kobasa, Darwyn

    2016-01-01

    Concerns with H5N1 influenza viruses include their prevalence in wild and domestic poultry, high mortality rate (~60%) in humans with some strains, lack of pre-existing immunity in humans, and the possibility that these viruses acquire mutations that enable efficient transmission between humans. H5 subtype viruses of Eurasian origin have recently appeared in wild and domestic bird populations in North America, and have led to the generation of new virus strains that are highly pathogenic in poultry. These new H5 HA containing viruses with their ability to evolve rapidly represent an unknown threat to humans in contact with infected poultry, and vaccination with an off-the-shelf vaccine may be impractical to provide protection to at-risk individuals. Instead, we have evaluated the efficacy of a formalin-inactivated vaccine, which could be derived directly from a circulating virus, to provide post-exposure protection. This strategy was evaluated using a prototypic highly pathogenic avian H5N1 strain, A/Vietnam/1203/2004, and demonstrated rapid induction of adaptive immune responses providing protection in a mammalian model of lethal infection. Additionally, this post-exposure vaccine was highly efficacious when administered 24 hours after exposure. This study offers a platform for developing effective post-exposure vaccines for treatment of highly virulent influenza infections. PMID:27405487

  13. Preliminary Proteomic Analysis of A549 Cells Infected with Avian Influenza Virus H7N9 and Influenza A Virus H1N1

    Ding, Xiaoman; Lu, Jiahai; Yu, Ruoxi; Wang, Xin; Wang, Ting; Dong, Fangyuan; Peng, Bo; Wu, Weihua; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Cheng, Jinquan; Yu, Muhua; Fang, Shisong

    2016-01-01

    A newly emerged H7N9 influenza virus poses high risk to human beings. However, the pathogenic mechanism of the virus remains unclear. The temporal response of primary human alveolar adenocarcinoma epithelial cells (A549) infected with H7N9 influenza virus and H1N1 influenza A virus (H1N1, pdm09) were evaluated using the proteomics approaches (2D-DIGE combined with MALDI-TOF-MS/MS) at 24, 48 and 72 hours post of the infection (hpi). There were 11, 12 and 33 proteins with significant different expressions (P<0.05) at 24, 48 and 72hpi, especially F-actin-capping protein subunit alpha-1 (CAPZA1), Ornithine aminotransferase (OAT), Poly(rC)-binding protein 1 (PCBP1), Eukaryotic translation initiation factor 5A-1 (EIF5A) and Platelet-activating factor acetylhydrolaseⅠb subunit beta (PAFAH1B2) were validated by western-blot analysis. The functional analysis revealed that the differential proteins in A549 cells involved in regulating cytopathic effect. Among them, the down-regulation of CAPZA1, OAT, PCBP1, EIF5A are related to the death of cells infected by H7N9 influenza virus. This is the first time show that the down-regulation of PAFAH1B2 is related to the later clinical symptoms of patients infected by H7N9 influenza virus. These findings may improve our understanding of pathogenic mechanism of H7N9 influenza virus in proteomics. PMID:27223893

  14. Development and applications of single-cycle infectious influenza A virus (sciIAV).

    Nogales, Aitor; Baker, Steven F; Domm, William; Martínez-Sobrido, Luis

    2016-05-01

    The diverse host range, high transmissibility, and rapid evolution of influenza A viruses justify the importance of containing pathogenic viruses studied in the laboratory. Other than physically or mechanically changing influenza A virus containment procedures, modifying the virus to only replicate for a single round of infection similarly ensures safety and consequently decreases the level of biosafety containment required to study highly pathogenic members in the virus family. This biological containment is more ideal because it is less apt to computer, machine, or human error. With many necessary proteins that can be deleted, generation of single-cycle infectious influenza A viruses (sciIAV) can be achieved using a variety of approaches. Here, we review the recent burst in sciIAV generation and summarize the applications and findings on this important human pathogen using biocontained viral mimics. PMID:26220478

  15. Virus genetic variations and evade from immune system, the present influenza challenges: review article

    Shahla Shahsavandi

    2015-10-01

    Full Text Available The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share molecular determinants to facilitate their replication in human host. So the emerge virus can be transmitted easily through person to person. The genetic variations of the influenza viruses, emerge and re-emerge of new antigenic variants, and transmission of avian influenza viruses to human may raise wide threat to public health and control of pandemic influenza. Vaccination, chemoprophylaxis with specific antiviral drugs, and personal protective non-pharmacological measures are tools to treat influenza virus infection. The emergence of drug resistant strains of influenza viruses under drug selective pressure and their limited efficacy in severe cases of influenza infections highlight the need to development of new therapies with alternative modes. In recent years several studies have been progressed to introduce components to be act at different stages of the viral life cycle with broad spectrum reactivity against mammalian and bird influenza subtypes. A wide variety of different antiviral strategies include inhibition of virus entry, blocking of viral replication or targeting of cellular signaling pathways have been explored. The current inactivated influenza vaccines are eliciting only B-cell responses. Application of the vaccines has been limited due to the emergence of the new virus antigenic variants. In recent decade development of gene vaccines by targeting various influenza virus proteins have been interested because significant potential for induction of both humoral and cell mediated immunity responses. Enhanced and directed immune responses to

  16. Clinical Accuracy of a PLEX-ID Flu Device for Simultaneous Detection and Identification of Influenza Viruses A and B

    Tang, Yi-Wei; Lowery, Kristin S; Valsamakis, Alexandra; Schaefer, Virginia C.; Chappell, James D.; White-Abell, Jill; Quinn, Criziel D.; Li, Haijing; Washington, Cicely A.; Cromwell, Jenna; Giamanco, Chantel M.; Forman, Michael; Holden, Jeffery; Rothman, Richard E.; Parker, Michelle L.

    2013-01-01

    Respiratory tract infections caused by influenza A and B viruses often present nonspecifically, and a rapid, high-throughput laboratory technique that can identify influenza viruses is clinically and epidemiologically desirable. The PLEX-ID Flu assay (Abbott Molecular Inc., Des Plaines, IL) incorporates multilocus PCR and electrospray ionization-mass spectrometry to detect and differentiate influenza A 2009 H1N1 (H1N1-p), seasonal H1N1 (H1N1-s), influenza A H3N2, and influenza B viruses in na...

  17. Determinants of glycan receptor specificity of H2N2 influenza A virus hemagglutinin.

    Karthik Viswanathan

    Full Text Available The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA. The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004 that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58 HA.

  18. Global circulation patterns of seasonal influenza viruses vary with antigenic drift

    Bedford, Trevor; Riley, Steven; Barr, Ian G.; Broor, Shobha; Chadha, Mandeep; Cox, Nancy J.; Daniels, Rodney S.; Gunasekaran, C. Palani; Hurt, Aeron C.; Kelso, Anne; Klimov, Alexander; Lewis, Nicola S.; Li, Xiyan; McCauley, John W.; Odagiri, Takato; Potdar, Varsha; Rambaut, Andrew; Shu, Yuelong; Skepner, Eugene; Smith, Derek J.; Suchard, Marc A.; Tashiro, Masato; Wang, Dayan; Xu, Xiyan; Lemey, Philippe; Russell, Colin A.

    2015-07-01

    Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.

  19. Possible repurposing of seasonal influenza vaccine for prevention of Zika virus infection

    Veljko Veljkovic; Slobodan Paessler

    2016-01-01

    The in silico analysis shows that the envelope glycoproteins E of Zika viruses (ZIKV) isolated in Asia, Africa and South and Central America encode highly conserved information determining their interacting profile and immunological properties. Previously it was shown that the same information is encoded in the primary structure of the hemagglutinin subunit 1 (HA1) from pdmH1N1 influenza A virus.  This similarity suggests possible repurposing of the seasonal influenza vaccine containing pdmH1...

  20. Examination of presence of specific antibodies against avian influenza virus in some species of wild birds

    Šekler Milanko; Ašanin Ružica; Krnjaić D.; Palić T.; Milić N.; Jovanović Tanja; Kovačević Dragana; Plavšić B.; Stojanović Dragica; Vidanović D.; Ašanin N.

    2009-01-01

    Infections caused by the avian influenza virus have been known for a long time and they are present, to a smaller or greater extent, in both extensive and intensive poultry production in many parts of the world. Epidemiological investigations have established a definite significance of the population of wild birds in maintaining and spreading this infection. Avian influenza is a zoonosis, and the virus has a great potential for causing mortality in humans, in particular its subtypes H5 and H7...