Immunoradiometric assay for cytomegalovirus-specific IgG antibodies

International Nuclear Information System (INIS)

Klapper, P.E.; Cleator, G.M.; Prinja-Wolks, D.; Morris, D.J.

1990-01-01

An immunoradiometric assay (radio-immunosorbent test; RIST) for the detection of IgG antibodies to human herpesvirus 4 [human cytomegalovirus (CMV)] has been developed. The technique utilizes CMV antigen passively adsorbed to a polyvinyl microtitration plate and a radiolabelled murine monoclonal anti-human IgG antibody to detect binding of human antibody to the 'solid phase' reagent. The assay was optimized, and its specifity confirmed by testing paired acute and convalescent sera from patients with acute CMV or other human herpesvirus infections. To determine the assay's sensitivity 1433 blood donor sera were examined. The RIST was more sensitive than a standard complement fixation (CFT). Use of a monoclonal anti-human IgG antibody in the RIST reduced non-specific binding to the control uninfected cell antigen such that blood donor sera could be tested in the assay using only a CMV antigen without generating an unacceptable false positive rate. (author). 23 refs.; 1 tab

Cytomegalovirus Congenital Cataract

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Ridha Wahyutomo

2011-06-01

Full Text Available Cytomegalovirus congenital infection is an infection caused by the the subfamily â Herpesviridae, during pregnancy. The incidence of infections among newborn infants is 1 %. One of the effects of congenitally acquired infection is the congenital cataract. A 6-year-old child complained to have a blurred vision diagnosed with cytomegalovirus congenital cataract. The diagnosis was confirmed by a positive serology testing for Ig M and Ig G CMV. The laboratory test using Giemsa staining to find inclusion bodies and a faster PCR could not be carried out (Sains Medika, 3(1:84-88.

Dasatinib-induced hemorrhagic colitis complicated with cytomegalovirus infection

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Aya Nakaya

2017-12-01

Full Text Available A 69-year-old man with chronic-phase chronic myeloid leukemia was initially treated with 100 mg dasatinib once a day. Despite a major molecular response within 9 months, he developed hemorrhagic colitis 32 months after starting dasatinib. Colonoscopy identified multiple hemorrhagic ulcers in the transverse colon. The pathological findings indicated cytomegalovirus infection. Dasatinib was stopped and he was started on ganciclovir. Three months later, colonoscopy confirmed the disappearance of the hemorrhagic ulcers. Dasatinib is a second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia. As a multi-kinase inhibitor that acts on SRC-family kinases, its broader off-target kinase-inhibitory activity may account for the adverse events of dasatinib. Although gastrointestinal bleeding is common in patients taking dasatinib, the combination of cytomegalovirus infection and hemorrhagic colitis in the absence of systemic immunodeficiency is rare. Based on this case of dasatinibinduced hemorrhagic colitis with cytomegalovirus infection, we describe a possible mechanism and effective treatment.

History of the molecular biology of cytomegaloviruses.

Science.gov (United States)

Stinski, Mark F

2014-01-01

The history of the molecular biology of cytomegaloviruses from the purification of the virus and the viral DNA to the cloning and expression of the viral genes is reviewed. A key genetic element of cytomegalovirus (the CMV promoter) contributed to our understanding of eukaryotic cell molecular biology and to the development of lifesaving therapeutic proteins. The study of the molecular biology of cytomegaloviruses also contributed to the development of antivirals to control the viral infection.

seroprevalence of cytomegalovirus infection amongst pregnant

African Journals Online (AJOL)

boaz

Cytomegalovirus (CMV) is a major public health problem throughout the world. It is the leading cause of ... Serum obtained from the blood samples were examined ... systems have been weakened by disease or drug ... fluids (e.g. saliva, urine, breast milk cervico-vaginal ... centrifuged on same day and the serum stored at -.

Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

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Annette Fink

2014-02-01

Full Text Available Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 Dd and that is immunodominant in BALB/c (H-2d haplotype mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E phase protein, the m164 epitope is presented already during the Immediate Early (IE phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164.

Mathematical Model of Cytomegalovirus (CMV) Disease

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Sriningsih, R.; Subhan, M.; Nasution, M. L.

2018-04-01

The article formed the mathematical model of cytomegalovirus (CMV) disease. Cytomegalovirus (CMV) is a type of herpes virus. This virus is actually not dangerous, but if the body's immune weakens the virus can cause serious problems for health and even can cause death. This virus is also susceptible to infect pregnant women. In addition, the baby may also be infected through the placenta. If this is experienced early in pregnancy, it will increase the risk of miscarriage. If the baby is born, it can cause disability in the baby. The model is formed by determining its variables and parameters based on assumptions. The goal is to analyze the dynamics of cytomegalovirus (CMV) disease spread.

Three-dimensional alginate spheroid culture system of murine osteosarcoma.

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Akeda, Koji; Nishimura, Akinobu; Satonaka, Haruhiko; Shintani, Ken; Kusuzaki, Katsuyuki; Matsumine, Akihiko; Kasai, Yuichi; Masuda, Koichi; Uchida, Atsumasa

2009-11-01

Osteosarcoma (OS) is the most common primary malignant tumor of the bone and often forms pulmonary metastases, which are the most important prognostic factor. For further elucidation of the mechanism underlying the progression and metastasis of human OS, a culture system mimicking the microenvironment of the tumor in vivo is needed. We report a novel three-dimensional (3D) alginate spheroid culture system of murine osteosarcoma. Two different metastatic clones, the parental Dunn and its derivative line LM8, which has a higher metastatic potential to the lungs, were encapsulated in alginate beads to develop the 3D culture system. The beads containing murine OS cells were also transplanted into mice to determine their metastatic potential in vivo. In this culture system, murine OS cells encapsulated in alginate beads were able to grow in a 3D structure with cells detaching from the alginate environment. The number of detaching cells was higher in the LM8 cell line than the Dunn cell line. In the in vivo alginate bead transplantation model, the rate of pulmonary metastasis was higher with LM8 cells compared with that of Dunn cells. The cell characteristics and kinetics in this culture system closely reflect the original malignant potential of the cells in vivo.

A possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin’s lymphoma

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Svozílková Petra

2013-01-01

Full Text Available Abstract Purpose To present a possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin’s lymphoma. Case presentation A 47-year-old woman presented with decreased visual acuity associated with white retinal lesions in both eyes. A history of pneumonia of unknown aetiology closely preceded the deterioration of vision. Five years previously the patient was diagnosed with follicular non-Hodgkin’s lymphoma. She was treated with a chemotherapy regimen comprised of cyclophosphamide, adriamycin, vincristin, and prednisone with later addition of the anti-CD20 antibody rituximab. She experienced a relapse 19 months later with involvement of the retroperitoneal lymph nodes, and commenced treatment with rituximab and 90Y-ibritumomab tiuxetan. A second relapse occurred 22 months after radioimmunotherapy and was treated with a combination of fludarabine, cyclophosphamide, and mitoxantrone followed by rituximab. The patient experienced no further relapses until the current presentation (April, 2010. Pars plana vitrectomy with vitreous fluid analysis was performed in the right eye. PCR testing confirmed the presence of cytomegalovirus in the vitreous. Atypical lymphoid elements, highly suspicious of malignancy were also found on cytologic examination. Intravenous foscarnet was administered continually for three weeks, followed by oral valganciclovir given in a dose of 900 mg twice per day. In addition, the rituximab therapy continued at three monthly intervals. Nevertheless, cessation of foscarnet therapy was followed by a recurrence of retinitis on three separate occasions during a 3-month period instigating its reinduction to the treatment regime after each recurrence. Conclusions Cytomegalovirus retinitis is an opportunistic infection found in AIDS patients as well as in bone marrow and solid organ transplant recipients being treated with systemic immunosuppressive drugs. This case presents a less

Clinical and morphological characteristics of malformations in infants with congenital cytomegalovirus infection and congenital toxoplasmosis

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L. Yu. Barycheva

2015-01-01

Full Text Available The results of following up infants with intrauterine infections and malformations were retrospectively analyzed. Infants with malformations were diagnosed as having congenital cytomegalovirus infection and congenital toxoplasmosis in 127 and 69 cases, respectively. The aim of the study was to characterize malformations in infants with congenital cytomegalovirus and congenital Toxoplasma infections. The infants with malformations in congenital cytomegalovirus infection were found to have higher mortality rates (61,4% than those with congenital toxoplasmosis (34,8%. Postmortem analysis indicated that there was a predominance of embryopathies in infants with congenital cytomegalovirus infection and that of fetopathies in those with congenital toxoplasmosis. The dead infants with congenital cytomegalovirus infection had more commonly developed visceral defects, including heart diseases, pneumopathies, gastrointestinal and genitourinary abnormalities; fetopathies of the central nervous system and eye were prevalent in congenital toxoplasmosis. The surviving children with congenital toxoplasmosis were more frequently observed to have disabling CNS and ocular sequels as obstructive hydrocephalus, infantile cerebral palsy, complete or partial blindness, and cerebrasthenic disorders than those with congenital cytomegalovirus infection. 

Controlling Cytomegalovirus: Helping the Immune System Take the Lead

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Patrick J. Hanley

2014-05-01

Full Text Available Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for thousands of years with an intricate balance of latency, immune evasion, and transmission. While upwards of 70% of humans have evidence of CMV infection, the majority of healthy people show little to no clinical symptoms of primary infection and CMV disease is rarely observed during persistent infection in immunocompetent hosts. Despite the fact that the majority of infected individuals are asymptomatic, immunologically, CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells that occasionally reactivate subclinically and present antigen to T cells, eventually causing the inflation of CMV-specific T cells until they can compromise up to 10% of the entire T cell repertoire. Because of this impact on the immune system, as well as its importance in fields such as stem cell and organ transplant, the relationship between CMV and the immune response has been studied in depth. Here we provide a review of many of these studies and insights into how CMV-specific T cells are currently being used therapeutically.

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

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Ballegaard, Vibe; Brændstrup, Peter; Pedersen, Karin Kaereby

2018-01-01

In people living with HIV (PLWHIV), coinfection with cytomegalovirus (CMV) has been associated with inflammation, immunological ageing, and increased risk of severe non-AIDS related comorbidity. The effect of CMV-specific immune responses on systemic inflammation, immune activation and T-cell sen...

γδ T cells confer protection against murine cytomegalovirus (MCMV.

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Camille Khairallah

2015-03-01

Full Text Available Cytomegalovirus (CMV is a leading infectious cause of morbidity in immune-compromised patients. γδ T cells have been involved in the response to CMV but their role in protection has not been firmly established and their dependency on other lymphocytes has not been addressed. Using C57BL/6 αβ and/or γδ T cell-deficient mice, we here show that γδ T cells are as competent as αβ T cells to protect mice from CMV-induced death. γδ T cell-mediated protection involved control of viral load and prevented organ damage. γδ T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3ε-/- mice from CMV-induced death confirming the protective antiviral role of γδ T cells. As observed in humans, different γδ T cell subsets were induced upon CMV challenge, which differentiated into effector memory cells. This response was observed in the liver and lungs and implicated both CD27+ and CD27- γδ T cells. NK cells were the largely preponderant producers of IFNγ and cytotoxic granules throughout the infection, suggesting that the protective role of γδ T cells did not principally rely on either of these two functions. Finally, γδ T cells were strikingly sufficient to fully protect Rag-/-γc-/- mice from death, demonstrating that they can act in the absence of B and NK cells. Altogether our results uncover an autonomous protective antiviral function of γδ T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new γδ T cell based therapies, especially useful in αβ T cell compromised patients.

Properties of virion transactivator proteins encoded by primate cytomegaloviruses

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Barry Peter A

2009-05-01

Full Text Available Abstract Background Human cytomegalovirus (HCMV is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1 genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. Results The UL82 homolog encoded by simian cytomegalovirus (SCMV, strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All

Report from the second cytomegalovirus and immunosenescence workshop

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Wills Mark

2011-10-01

Full Text Available Abstract The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.

Cytomegalovirus replicon-based regulation of gene expression in vitro and in vivo.

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Hermine Mohr

Full Text Available There is increasing evidence for a connection between DNA replication and the expression of adjacent genes. Therefore, this study addressed the question of whether a herpesvirus origin of replication can be used to activate or increase the expression of adjacent genes. Cell lines carrying an episomal vector, in which reporter genes are linked to the murine cytomegalovirus (MCMV origin of lytic replication (oriLyt, were constructed. Reporter gene expression was silenced by a histone-deacetylase-dependent mechanism, but was resolved upon lytic infection with MCMV. Replication of the episome was observed subsequent to infection, leading to the induction of gene expression by more than 1000-fold. oriLyt-based regulation thus provided a unique opportunity for virus-induced conditional gene expression without the need for an additional induction mechanism. This principle was exploited to show effective late trans-complementation of the toxic viral protein M50 and the glycoprotein gO of MCMV. Moreover, the application of this principle for intracellular immunization against herpesvirus infection was demonstrated. The results of the present study show that viral infection specifically activated the expression of a dominant-negative transgene, which inhibited viral growth. This conditional system was operative in explant cultures of transgenic mice, but not in vivo. Several applications are discussed.

Inhibition of Human Cytomegalovirus pUL89 Terminase Subunit Blocks Virus Replication and Genome Cleavage.

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Wang, Yan; Mao, Lili; Kankanala, Jayakanth; Wang, Zhengqiang; Geraghty, Robert J

2017-02-01

The human cytomegalovirus terminase complex cleaves concatemeric genomic DNA into unit lengths during genome packaging and particle assembly. This process is an attractive drug target because cleavage of concatemeric DNA is not required in mammalian cell DNA replication, indicating that drugs targeting the terminase complex could be safe and selective. One component of the human cytomegalovirus terminase complex, pUL89, provides the endonucleolytic activity for genome cleavage, and the domain responsible is reported to have an RNase H-like fold. We hypothesize that the pUL89 endonuclease activity is inhibited by known RNase H inhibitors. Using a novel enzyme-linked immunosorbent assay (ELISA) format as a screening assay, we found that a hydroxypyridonecarboxylic acid compound, previously reported to be an inhibitor of human immunodeficiency virus RNase H, inhibited pUL89 endonuclease activity at low-micromolar concentrations. Further characterization revealed that this pUL89 endonuclease inhibitor blocked human cytomegalovirus replication at a relatively late time point, similarly to other reported terminase complex inhibitors. Importantly, this inhibitor also prevented the cleavage of viral genomic DNA in infected cells. Taken together, these results substantiate our pharmacophore hypothesis and validate our ligand-based approach toward identifying novel inhibitors of pUL89 endonuclease. Human cytomegalovirus infection in individuals lacking a fully functioning immune system, such as newborns and transplant patients, can have severe and debilitating consequences. The U.S. Food and Drug Administration-approved anti-human cytomegalovirus drugs mainly target the viral polymerase, and resistance to these drugs has appeared. Therefore, anti-human cytomegalovirus drugs from novel targets are needed for use instead of, or in combination with, current polymerase inhibitors. pUL89 is a viral ATPase and endonuclease and is an attractive target for anti-human cytomegalovirus

Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.

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Simone Thomas

2015-07-01

Full Text Available Reactivation of human cytomegalovirus (HCMV can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease.

Prevalence of cytomegalovirus antibodies in blood donars at the ...

African Journals Online (AJOL)

Background: Cytomegalovirus (CMV) infection in susceptible patients is associated with serious morbidity and a high mortality. Transmission of cytomegalovirus infection through blood transfusion is markedly reduced by transfusion of CMV seronegative blood products, or by transfusion of leucodepleted blood products.

Cytomegalovirus infection in NICU admitted neonates in Boushehr

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Maryam Sanjideh

2016-01-01

Full Text Available Background: Cytomegalovirus is the most prevalent cause of congenital infections and the most important cause of congenital deafness. Which it's spread is about 0.64% of all birth which differ based on geolocation, race and socioeconomically situations. This proposal accomplished in the end of July until middle of February 2014 with the goal of studying Cytomegalovirus infection distribution among newborns who are hospitalized in Bushehr Shohadaye Khalij Fars hospital NICU. Material & Method: 80 urine samples were collected between July until February 2014 in NICU of Bushehr Khalij Fars hospitalized neonates. Samples were tested by PCR method on urine samples to find if they are infected by cytomegalovirus. Results: Mean age of neonates was 30.59±9.30 days. Only one newborn under 30 days had Cytomegalovirus and 11 cases older than 30 days had positive reaction. The relation between age and CMV seropositivity was statistically valid (p<0.05.this means only 1.2% of newborns are CMV and 55% are older than 1 month. Conclusion: The pattern of CMV seropositivity shows that most infections may be acquired from environment. According to low prevalence of congenital CMV infection, there is no need to introduce preventive methods and following present guidelines is enough.

Colonic stenosis post-necrotizing enterocolitis in term newborn with acquired cytomegalovirus infection.

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Marseglia, L; Manti, S; D'Angelo, G; Lima, M; Impellizzeri, P; Romeo, C; Gitto, E

2015-01-01

Necrotizing enterocolitis is a gastrointestinal emergency typical of premature infants. Intestinal strictures infrequently complicate medical or surgical treatment of necrotizing enterocolitis. Postnatal cytomegalovirus infection with gastrointestinal linvolvement has occasionally been described in subjects with necrotizing enterocolitis. We report the case of a full term infant presenting necrotizing enterocolitis, acquired cytomegalovirus infection and post necrotizing enterocolitis colonic stricture.List of abbreviations: necrotizing enterocolitis = NEC,cytomegalovirus = CMV. Celsius.

Symptomatic primary cytomegalovirus infection in a HIV-positive pregnant woman.

LENUS (Irish Health Repository)

Bergin, Sarah

2014-12-01

We describe a case of symptomatic primary Cytomegalovirus infection in a HIV-positive pregnant woman on antiretroviral treatment with a CD4 count >200 × 10(6)\\/l requiring intravenous ganciclovir. No adverse consequences from ganciclovir or evidence of congenital Cytomegalovirus infection were found.

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

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Torsten Sacher

2011-11-01

Full Text Available Cytomegalovirus (CMV is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+ heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+ transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+ recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.

Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus.

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Arapovic, Jurica; Lenac, Tihana; Antulov, Ronald; Polic, Bojan; Ruzsics, Zsolt; Carayannopoulos, Leonidas N; Koszinowski, Ulrich H; Krmpotic, Astrid; Jonjic, Stipan

2009-08-01

The NKG2D receptor is one of the most potent activating natural killer cell receptors involved in antiviral responses. The mouse NKG2D ligands MULT-1, RAE-1, and H60 are regulated by murine cytomegalovirus (MCMV) proteins m145, m152, and m155, respectively. In addition, the m138 protein interferes with the expression of both MULT-1 and H60. We show here that one of five RAE-1 isoforms, RAE-1delta, is resistant to downregulation by MCMV and that this escape has functional importance in vivo. Although m152 retained newly synthesized RAE-1delta and RAE-1gamma in the endoplasmic reticulum, no viral regulator was able to affect the mature RAE-1delta form which remains expressed on the surfaces of infected cells. This differential susceptibility to downregulation by MCMV is not a consequence of faster maturation of RAE-1delta compared to RAE-1gamma but rather an intrinsic property of the mature surface-resident protein. This difference can be attributed to the absence of a PLWY motif from RAE-1delta. Altogether, these findings provide evidence for a novel mechanism of host escape from viral immunoevasion of NKG2D-dependent control.

In silico pattern-based analysis of the human cytomegalovirus genome.

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Rigoutsos, Isidore; Novotny, Jiri; Huynh, Tien; Chin-Bow, Stephen T; Parida, Laxmi; Platt, Daniel; Coleman, David; Shenk, Thomas

2003-04-01

More than 200 open reading frames (ORFs) from the human cytomegalovirus genome have been reported as potentially coding for proteins. We have used two pattern-based in silico approaches to analyze this set of putative viral genes. With the help of an objective annotation method that is based on the Bio-Dictionary, a comprehensive collection of amino acid patterns that describes the currently known natural sequence space of proteins, we have reannotated all of the previously reported putative genes of the human cytomegalovirus. Also, with the help of MUSCA, a pattern-based multiple sequence alignment algorithm, we have reexamined the original human cytomegalovirus gene family definitions. Our analysis of the genome shows that many of the coded proteins comprise amino acid combinations that are unique to either the human cytomegalovirus or the larger group of herpesviruses. We have confirmed that a surprisingly large portion of the analyzed ORFs encode membrane proteins, and we have discovered a significant number of previously uncharacterized proteins that are predicted to be G-protein-coupled receptor homologues. The analysis also indicates that many of the encoded proteins undergo posttranslational modifications such as hydroxylation, phosphorylation, and glycosylation. ORFs encoding proteins with similar functional behavior appear in neighboring regions of the human cytomegalovirus genome. All of the results of the present study can be found and interactively explored online (http://cbcsrv.watson.ibm.com/virus/).

Mondini dysplasia and congenital cytomegalovirus infection.

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Bauman, N M; Kirby-Keyser, L J; Dolan, K D; Wexler, D; Gantz, B J; McCabe, B F; Bale, J F

1994-01-01

We report a case of bilateral temporal bone anomalies in a child with symptomatic congenital cytomegalovirus infection and severe, bilateral sensorineural hearing loss identified at 3 months of age. High-resolution temporal bone computed tomography (HRCT) revealed bilateral findings of a short, malformed cochlea lacking an interscalar septum, a short and wide internal auditory canal, and an enlarged vestibular aqueduct, features diagnostic of bilateral Mondini dysplasia. To determine the importance of this observation, we completed HRCT in five additional children between 7 months and 9 years of age who had evidence of symptomatic congenital cytomegalovirus infection. One child with profound sensorineural hearing loss had severe bilateral temporal bone dysplasia with a small cochlea lacking an interscalar septum, an abnormal vestibule, and a large cochlear aqueduct. Of the remaining four children, hearing thresholds ranged from normal to profoundly decreased, but their HRCT scans were normal to visual inspection. When inner ear dimensions of these temporal bones were compared with norms established by Pappas and coworkers, however, seven of the eight ears had short cochleas and narrow lateral semicircular canals, and three ears had short or narrow vestibules. These results indicate that congenital cytomegalovirus infection may cause anomalies or growth disturbances of the temporal bone.

Cytomegalovirus Hepatitis During Pregnancy

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Ying Chan

1995-01-01

Full Text Available Background: Although cytomegalovirus (CMV is an uncommon cause of viral hepatitis during pregnancy, a definitive diagnosis is important because of the potential for congenital CMV. In the case reported here, a diagnosis of hepatitis caused by CMV was made after the more common viral pathogens had been ruled out.

Two cases of cytomegalovirus panuveitis in immunocompetent patients

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Masato Sakai

2018-06-01

Full Text Available Purpose: To report two cases of panuveitis in immunocompetent patients in which cytomegalovirus was involved. Observation: Case 1 was a 46-year-old man who had a history of recurrent anterior chamber inflammations in his left eye. After Nd:YAG laser posterior capsulotomy, he developed panuveitis with vitreous haze and periphlebitis. Polymerase chain reaction (PCR examination revealed the presence of cytomegalovirus (CMV DNA in the anterior chamber (AC. He responded well to a series of intravitreal injections of ganciclovir (GCV. Case 2 was a 63-year-old woman who had a history of recurrent anterior uveitis in her left eye. Two years after cataract surgery, AC inflammation, diffuse vitreous haze, and periphlebitis had developed. CMV DNA was detected in the AC. Intravitreal injections of GCV and oral valganciclovir were administered, and ocular inflammation finally improved. Conclusions: and importance: We experienced two cases of CMV panuveitis in immunocompetent adults, both of which responded well to anti-viral therapies. Keywords: Cytomegalovirus, Panuveitis, Immunocompetent, Intravitreal injection, PCR

Cytomegalovirus infection in pediatric rheumatic diseases: a review

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Wolf Dana G

2010-05-01

Full Text Available Abstract Human cytomegalovirus (HCMV is familiar to pediatric rheumatologists mainly as a cause of opportunistic disease in pharmacologically immune suppressed patients. However, HCMV also has a variety of immuno-modulatory effects, through which it may influence the course of rheumatic conditions. In this article we discuss the interplay between HCMV and the immune system, and review the clinical manifestations, diagnosis, and treatment of HCMV infection in children with rheumatic disease.

The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.

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Baca Chan

2017-05-01

Full Text Available The type I interferon (IFN response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV that shuts down signaling following pattern recognition receptor (PRR sensing. Screening of an MCMV open reading frame (ORF library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR. Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR. M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

Cytomegalovirus (CMV) Infection Causes Degeneration of Cochlear Vasculature and Hearing Loss in a Mouse Model.

Science.gov (United States)

Carraro, Mattia; Almishaal, Ali; Hillas, Elaine; Firpo, Matthew; Park, Albert; Harrison, Robert V

2017-04-01

Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6 weeks of age, cochlear function was monitored using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measures. Histological assessment of cochlear vasculature using a corrosion cast technique was made at 8 weeks. Vascular casts of mCMV-damaged cochleas, and those of untreated control animals, were examined using scanning electron microscopy. We find very large variations in the degree of vascular damage in animals given identical viral injections (2000 pfu). The primary lesion caused by CMV infection is to the stria vascularis and to the adjacent spiral limbus capillary network. Capillary beds of the spiral ligament are generally less affected. The initial vascular damage is found in the mid-apical turn and appears to progress to more basal cochlear regions. After viral migration to the inner ear, the stria vascularis is the primary affected structure. We suggest that initial auditory threshold losses may relate to the poor development or maintenance of the endocochlear potential caused by strial dysfunction. Our increased understanding of the pathogenesis of CMV-related hearing loss is important for defining methods for early detection and treatment.

Immunoradiometric assay for cytomegalovirus-specific IgG antibodies; Assay development and evaluation in blood transfusion practice

Energy Technology Data Exchange (ETDEWEB)

Klapper, P.E.; Cleator, G.M.; Prinja-Wolks, D.; Morris, D.J. (Medical School, Manchester (United Kingdom). Department of Medical microbiology, Virology Unit); Morell, G. (Regional Blood Transfusion Centre, manchester (United Kingdom))

1990-03-01

An immunoradiometric assay (radio-immunosorbent test; RIST) for the detection of IgG antibodies to human herpesvirus 4 (human cytomegalovirus (CMV)) has been developed. The technique utilizes CMV antigen passively adsorbed to a polyvinyl microtitration plate and a radiolabelled murine monoclonal anti-human IgG antibody to detect binding of human antibody to the 'solid phase' reagent. The assay was optimized, and its specifity confirmed by testing paired acute and convalescent sera from patients with acute CMV or other human herpesvirus infections. To determine the assay's sensitivity 1433 blood donor sera were examined. The RIST was more sensitive than a standard complement fixation (CFT). Use of a monoclonal anti-human IgG antibody in the RIST reduced non-specific binding to the control uninfected cell antigen such that blood donor sera could be tested in the assay using only a CMV antigen without generating an unacceptable false positive rate. (author). 23 refs.; 1 tab.

[Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case report].

Science.gov (United States)

Uribe, Luis Guillermo; Pérez, María Alejandra; Lara, Camilo Andrés; Rueda, Natalia; Hernández, Javier Augusto

2017-12-01

Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest prevalence in immunocompromised patients. Reactivation has decreased after the introduction of highly active antiretroviral therapy (HAART). Encephalitis has been reported in the coinfection as one of the most frequent presentations.We present the case of a young adult patient with HIV infection and rapid neurological deterioration due to classic clinical symptoms and signs of the Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with images by nuclear magnetic resonance typical of the syndrome, and identification of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed to control the symptoms with neurological sequelae in progression towards improvement.This is one of the few cases reported in the literature of Wernicke syndrome secondary to cytomegalovirus encephalitis.

Cytomegalovirus (CMV) Infection: A Guide for Patients and Families After Stem Cell Transplant

Science.gov (United States)

... Infection: A Guide for Patients and Families after Stem Cell Transplant What is cytomegalovirus (CMV)? Cytomegalovirus (CMV), a ... weakened by medicines that you must take after stem cell transplant and by the transplant itself. Your body ...

New PCR diagnostic systems for the detection and quantification of porcine cytomegalovirus (PCMV).

Science.gov (United States)

Morozov, Vladimir A; Morozov, Alexey V; Denner, Joachim

2016-05-01

Pigs are frequently infected with porcine cytomegalovirus (PCMV). Infected adult animals may not present with symptoms of disease, and the virus remains latent. However, the virus may be transmitted to human recipients receiving pig transplants. Recently, it was shown that pig-to-non-human-primate xenotransplantations showed 2 to 3 times lower transplant survival when the donor pig was infected with PCMV. Therefore, highly sensitive methods are required to select virus-free pigs and to examine xenotransplants. Seven previously established PCR detection systems targeting the DNA polymerase gene of PCMV were examined by comparison of thermodynamic parameters of oligonucleotides, and new diagnostic nested PCR and real-time PCR systems with improved parameters and high sensitivity were established. The detection limit of conventional PCR was estimated to be 15 copies, and that of the nested PCR was 5 copies. The sensitivity of the real-time PCR with a TaqMan probe was two copies. An equal efficiency of the newly established detection systems was shown by parallel testing of DNA from sera and blood of six pigs, identifying the same animals as PCMV infected. These new diagnostic PCR systems will improve the detection of PCMV and therefore increase the safety of porcine xenotransplants.

Evaluating the Effects of Cytomegalovirus Glycoprotein B on the Maturation and Function of Monocyte-derived dendritic cells

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Afsson shariat

2015-11-01

Full Text Available Background & Objectives: Interaction of cytomegalovirus glycoprotein B with toll-like receptors of dendritic cells leads to early signaling and innate immune responses. The aim of this study is to evaluate the effects of cytomegalovirus glycoprotein B on the maturation and function of monocyte-derived dendritic cells in treated groups in comparison with control groups. Materials & Methods: Blood samples were taken from 5 healthy volunteers. Following the generation of monocyte-derived dendritic cells on the fifth day of cell culture, half of the immature dendritic cells were treated with cytomegalovirus glycoprotein B, and the rest of them were induced to mature dendritic untreated cells and were used as the control group. The maturation and function of dendritic cells were evaluated in these two groups. Results: The gene expression level of toll-like receptor-4 significantly increased in the group treated with glycoprotein B (p < 0.05, whereas there were no significant differences in the expression rates of CD83, CD86, CD1a, and HLA-DR and the secretion of IL-23 from monocyte-derived dendritic cells between the treated groups and the controls. Conclusion: The increase in the gene expression of toll-like receptor-4 in monocyte-derived dendritic cells treated with cytomegalovirus glycoprotein B showed that cell contact is required to elicit cellular antiviral response and toll-like receptor activation. Thus, it is critical to recognize the viral and cellular determinants of the immune system in order to develop new therapeutic strategies against cytomegalovirus.

Family poverty is associated with cytomegalovirus antibody titers in U.S. children.

Science.gov (United States)

Dowd, Jennifer B; Palermo, Tia M; Aiello, Allison E

2012-01-01

Early life environmental and psychological influences are thought to play an important role in the development of the immune system. Antibody response to latent herpesviruses has been used as an indirect measure of cell-mediated immune function but has seldom been applied to younger age groups. We used data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) to test for an association between family poverty and continuous antibody response to cytomegalovirus in U.S. children aged 6-16 (N = 2,226) using ordinary least squares regression. Poverty was significantly associated with increased antibody levels among seropositive individuals. The association between income and antibody levels exhibited a threshold effect, with additional income beyond the poverty line not associated with increased antibody titers. This relationship was more robust among older compared with younger children. Early life social factors such as family poverty could have detrimental impacts on the developing immune system, with potentially important consequences for later life health outcomes. Exposure to socioeconomic stressors for longer periods during childhood may further enhance alterations in immune response to cytomegalovirus.

A novel polyclonal antibody against human cytomegalovirus ...

African Journals Online (AJOL)

User

2011-05-09

May 9, 2011 ... The identification of the synthetic peptide antibody was confirmed by ... cell virus transmission and fusion of infected cells, as well ..... Cytomegalovirus and Epstein-. Barr virus subtypes-The search for clinical significance.

Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy.

Science.gov (United States)

Rawlinson, William D; Boppana, Suresh B; Fowler, Karen B; Kimberlin, David W; Lazzarotto, Tiziana; Alain, Sophie; Daly, Kate; Doutré, Sara; Gibson, Laura; Giles, Michelle L; Greenlee, Janelle; Hamilton, Stuart T; Harrison, Gail J; Hui, Lisa; Jones, Cheryl A; Palasanthiran, Pamela; Schleiss, Mark R; Shand, Antonia W; van Zuylen, Wendy J

2017-06-01

Congenital cytomegalovirus is the most frequent, yet under-recognised, infectious cause of newborn malformation in developed countries. Despite its clinical and public health importance, questions remain regarding the best diagnostic methods for identifying maternal and neonatal infection, and regarding optimal prevention and therapeutic strategies for infected mothers and neonates. The absence of guidelines impairs global efforts to decrease the effect of congenital cytomegalovirus. Data in the literature suggest that congenital cytomegalovirus infection remains a research priority, but data are yet to be translated into clinical practice. An informal International Congenital Cytomegalovirus Recommendations Group was convened in 2015 to address these questions and to provide recommendations for prevention, diagnosis, and treatment. On the basis of consensus discussions and a review of the literature, we do not support universal screening of mothers and the routine use of cytomegalovirus immunoglobulin for prophylaxis or treatment of infected mothers. However, treatment guidelines for infected neonates were recommended. Consideration must be given to universal neonatal screening for cytomegalovirus to facilitate early detection and intervention for sensorineural hearing loss and developmental delay, where appropriate. The group agreed that education and prevention strategies for mothers were beneficial, and that recommendations will need continual updating as further data become available. Copyright © 2017 Elsevier Ltd. All rights reserved.

Murine model for congenital CMV infection and hearing impairment

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Tao Liu

2011-02-01

Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is the leading cause of sensorineural hearing loss (SNHL, and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. Methods We established the congenital murine cytomegalovirus (MCMV infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Results Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. Conclusions The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.

Congenital cytomegalovirus related intestinal malrotation: a case report.

Science.gov (United States)

Colomba, Claudia; Giuffrè, Mario; La Placa, Simona; Cascio, Antonio; Trizzino, Marcello; De Grazia, Simona; Corsello, Giovanni

2016-12-07

Cytomegalovirus is the most common cause of congenital infection in the developed countries. Gastrointestinal involvement has been extensively described in both adult and paediatric immunocompromised patients but it is infrequent in congenital or perinatal CMV infection. We report on a case of coexistent congenital Cytomegalovirus infection with intestinal malrotation and positive intestinal Cytomegalovirus biopsy. At birth the neonate showed clinical and radiological evidence of intestinal obstruction. Meconium passed only after evacuative nursing procedures; stooling pattern was irregular; gastric residuals were bile-stained. Laparatomy revealed a complete intestinal malrotation and contextually gastrointestinal biopsy samples of the appendix confirmed the diagnosis of CMV gastrointestinal disease. Intravenous ganciclovir was initiated for 2 weeks, followed by oral valgancyclovir for 6 month. CMV-induced proinflammatory process may be responsible of the interruption of the normal development of the gut or could in turn lead to a disruption in the normal development of the gut potentiating the mechanism causing malrotation. We suggest the hypothesis that an inflammatory process induced by CMV congenital infection may be responsible, in the early gestation, of the intestinal end-organ disease, as the intestinal malrotation. CMV infection should always be excluded in full-term infants presenting with colonic stricture or malrotation.

Seroprevalence of cytomegalovirus Antibodies among pregnant ...

African Journals Online (AJOL)

Background: Cytomegalovirus is a common virus that infects most people at some time during their lives. It becomes dormant for a while and may reactivate later. In pregnant women, intrauterine infection may be associated with congenital abnormalities, intrauterine growth retardation and intrauterine death of the fetus as ...

Detection of cytomegalovirus in blood donors by PCR using the digene SHARP signal system assay: effects of sample preparation and detection methodology.

OpenAIRE

Krajden, M; Shankaran, P; Bourke, C; Lau, W

1996-01-01

Cytomegalovirus (CMV) is an important cause of transfusion-associated morbidity and mortality; however, only 0.4 to 12% of the blood products obtained from seropositive blood donors transmit infection. The effects of three commercially available whole-blood sample preparation kits on the detection of CMV PCR products by a semiquantitative adaptation of the Digene SHARP Signal System Assay (DSSSA) in samples from volunteer blood donors was assessed. Of 101 samples from seropositive blood donor...

21 CFR 866.3175 - Cytomegalovirus serological reagents.

Science.gov (United States)

2010-04-01

... cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal... (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has...

Baicalein induces cell death in murine T cell lymphoma via inhibition of thioredoxin system.

Science.gov (United States)

Patwardhan, Raghavendra S; Pal, Debojyoti; Checker, Rahul; Sharma, Deepak; Sandur, Santosh K

2017-10-01

We have earlier demonstrated the radioprotective potential of baicalein using murine splenic lymphocytes. Here, we have studied the effect of baicalein on murine T cell lymphoma EL4 cells and investigated the underlying mechanism of action. We observed that baicalein induced a dose dependent cell death in EL4 cells in vitro and significantly reduced the frequency of cancer stem cells. Previously, we have reported that murine and human T cell lymphoma cells have increased oxidative stress tolerance capacity due to active thioredoxin system. Hence, we monitored the effect of baicalein on thioredoxin system in EL4 cells. Docking studies revealed that baicalein could bind to the active site of thioredoxin reductase. Baicalein treatment led to significant reduction in the activity of thioredoxin reductase and nuclear levels of thioredoxin-1 thereby increasing ASK1 levels and caspase-3 activity. Interestingly, CRISPR-Cas9 based knock-out of ASK1 or over-expression of thioredoxin-1 abolished anti-tumor effects of baicalein in EL4 cells. Further, baicalein administration significantly reduced intra-peritoneal tumor burden of EL4 cells in C57BL/6 mice. Thus, our study describes anti-tumor effects of baicalein in EL4 cells via inhibition of thioredoxin system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells.

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Tršan, Tihana; Vuković, Kristina; Filipović, Petra; Brizić, Ana Lesac; Lemmermann, Niels A W; Schober, Kilian; Busch, Dirk H; Britt, William J; Messerle, Martin; Krmpotić, Astrid; Jonjić, Stipan

2017-08-01

Designing CD8 + T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 + T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. CMV vector expressing RAE-1γ potentiated expansion of KLRG1 + CD8 + T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long-term maintenance of epitope-specific CD8 + T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8 + T-cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8 + T-cell sensitive tumors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

EBI3 regulates the NK cell response to mouse cytomegalovirus infection

DEFF Research Database (Denmark)

Jensen, Helle; Chen, Shih-Yu; Folkersen, Lasse Westergaard

2017-01-01

Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induc......Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection....... The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFNγ production and CD69 expression, were not affected in EBI3-deficient (Ebi3-/-) C57BL/6 (B6) mice during MCMV infection. Furthermore, comparable levels of early viral...... replication in spleen and liver were observed in MCMV-infected Ebi3-/- and wild-type (WT) B6 mice. Interestingly, the viral load in salivary glands and oral lavage was strongly decreased in the MCMV-infected Ebi3-/- B6 mice, suggesting that EBI3 plays a role in the establishment of MCMV latency. We detected...

Multiorgan involvement due to cytomegalovirus infection in AIDS

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Shounak Majumder

Full Text Available Cytomegalovirus (CMV infection is a relatively late complication of AIDS. Like other viruses contributing to co-morbidity of HIV infection, cytomegalovirus has the propensity to cause multiorgan involvement. We report the case of a 34-year-old seropositive man who presented with bilateral lower limb weakness and symptomatic pallor. He was already on antiretroviral drugs for a month prior to presentation. Detailed clinical examination and laboratory investigations revealed cytomegalovirus polyradiculoneuropathy associated with bone marrow dysplasia. Dysplasia of haematopoeitic cell lines occurs in 30% to 70% of HIV infected patients, and is often indistinguishable from myelodysplastic syndrome. However, in our case, the bone marrow picture reverted back to normal with treatment of the CMV infection, pointing to a possible role of CMV as the causative agent of bone marrow dysplasia. Moreover, CMV has been incriminated as a pathogen producing the immune reconstitution inflammatory syndrome. The onset of the disease in our case one month after initiation of HAART strongly raises the possibility of this being a case of CMV related IRIS. This is the first reported case where IRIS has presented with CMV polyradiculoneuropathy and bone marrow dysplasia. We would like to highlight that in today's era of HIV care, clinicians should be aware of the possibility of multiorgan involvement by CMV, for appropriate management of this disease in the background of AIDS.

Overlapping transcription structure of human cytomegalovirus

Indian Academy of Sciences (India)

Transcription of human cytomegalovirus UL/b′ region has been studied extensively for some genes. In this study, transcripts of the UL140 and UL141, two of the UL/b′ genes, were identified in late RNAs of three HCMV isolates using Northern blot hybridization, cDNA library screening and RACE-PCR. At least three ...

Overlapping transcription structure of human cytomegalovirus ...

Indian Academy of Sciences (India)

2013-01-21

Jan 21, 2013 ... Transcription of human cytomegalovirus UL/b′ region has been studied extensively for some genes. In this study, transcripts of the UL140 and UL141, two of the UL/b′ genes, were identified in late RNAs of three HCMV isolates using Northern blot hybridization, cDNA library screening and RACE-PCR.

Bilateral cytomegalovirus retinitis in a child with acute lymphoblastic leukemia while on maintenance chemotherapy

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Vaidehi S. Dedania

2016-08-01

Full Text Available We report a case of bilateral cytomegalovirus retinitis in a 12 year-old with neutropenic fever after maintenance chemotherapy for acute lymphoblastic leukemia. Ophthalmologic examination for photophobia prompted a diagnosis of cytomegalovirus retinitis. With early diagnosis and prompt treatment, this patient had a favorable visual outcome.

Cytomegalovirus vaccines under clinical development

OpenAIRE

Schleiss, Mark R

2016-01-01

Abstract Congenital cytomegalovirus (CMV) infection is the most common infectious cause of disability in newborn infants. CMV also causes serious disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. In otherwise healthy children and adults, primary CMV infection rarely causes illness. However, even asymptomatic CMV infections may predispose an individual towards an increased risk of atherosclerosis, cancer and immune senescence over the life course, although...

A novel polyclonal antibody against human cytomegalovirus ...

African Journals Online (AJOL)

Future research should be directed to epitope screening of synthetic HMCV peptides, which could help to understand HCMV infection and virus-neutralising antibodies more fully and to prepare HCMV vaccines and antiviral drugs. Key words: Human cytomegalovirus, AD169 strain, Towne strains, polyclonal antibody.

Reversible bull's-eye maculopathy associated with intravitreal fomivirsen therapy for cytomegalovirus retinitis.

Science.gov (United States)

Stone, T W; Jaffe, G J

2000-08-01

To report two cases in which a bull's eye maculopathy developed after intravitreal injection of fomivirsen. Case reports. A 50-year-old man with acquired immunodeficiency syndrome (AIDS) and refractory cytomegalovirus retinitis developed bull's-eye pigmentary changes in the macula of the right eye after initiating therapy with fomivirsen (Vitravene; CIBA Vision, Atlanta, Georgia) intravitreal injections. These pigmentary changes resolved upon cessation of treatment. A 36-year-old man with AIDS and refractory bilateral cytomegalovirus retinitis developed bull's-eye pigmentary changes in both eyes during bilateral intravitreal treatment with fomivirsen. Vision was not affected. These changes resolved after treatment with fomivirsen was stopped. Fomivirsen, a new medication for the treatment of refractory cytomegalovirus retinitis, may cause a bull's-eye maculopathy in some patients. The bull's-eye maculopathy is reversible and does not appear to affect vision.

Signal peptide-dependent inhibition of MHC class I heavy chain translation by rhesus cytomegalovirus.

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Colin J Powers

2008-10-01

Full Text Available The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit MHC-I assembly with viral peptides, thus preventing cytotoxic T cell recognition. Since HCMV lacking US2-11 is no longer able to block assembly and transport of MHC-I, we examined whether this is also observed for RhCMV lacking the corresponding region. Unexpectedly, recombinant RhCMV lacking US2-11 was still able to inhibit MHC-I expression in infected fibroblasts, suggesting the presence of an additional MHC-I evasion mechanism. Progressive deletion analysis of RhCMV-specific genomic regions revealed that MHC-I expression is fully restored upon additional deletion of rh178. The protein encoded by this RhCMV-specific open reading frame is anchored in the endoplasmic reticulum membrane. In the presence of rh178, RhCMV prevented MHC-I heavy chain (HC expression, but did not inhibit mRNA transcription or association of HC mRNA with translating ribosomes. Proteasome inhibitors stabilized a HC degradation intermediate in the absence of rh178, but not in its presence, suggesting that rh178 prevents completion of HC translation. This interference was signal sequence-dependent since replacing the signal peptide with that of CD4 or murine HC rendered human HCs resistant to rh178. We have identified an inhibitor of antigen presentation encoded by rhesus cytomegalovirus unique in both its lack of homology to any other known protein and in its mechanism of action. By preventing signal sequence-dependent HC translocation, rh178 acts prior to US2, US3 and US11 which attack MHC-I proteins after protein synthesis is completed. Rh178 is the first viral protein known to interfere at this step of the MHC-I pathway, thus taking advantage of the conserved nature of HC leader peptides, and represents a new mechanism of translational interference.

Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

Science.gov (United States)

Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

2016-01-01

Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus

OpenAIRE

Abou, Magali; Dällenbach, Patrick

2013-01-01

Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported.

[Update on congenital and neonatal herpes infections: infection due to cytomegalovirus and herpes simplex].

Science.gov (United States)

Baquero-Artigao, F

2017-05-17

Newborn infants are a population which is especially susceptible to viral infections that frequently affect the central nervous system. Herpes infections can be transmitted to the foetus and to the newborn infant, and give rise to severe clinical conditions with long-term sensory and cognitive deficits. Two thirds of newborn infants with encephalitis due to herpes simplex virus and half of the children with symptomatic congenital infection by cytomegalovirus develop sequelae, which results in high community health costs in the long term. Fortunately, the better knowledge about these infections gained in recent years together with the development of effective antiviral treatments have improved the patients' prognosis. Valganciclovir (32 mg/kg/day in two doses for six months) prevents the development of hypoacusis and improves the neurological prognosis in symptomatic congenital infection due to cytomegalovirus. Acyclovir (60 mg/kg/day in three doses for 2-3 weeks) prevents the development of severe forms in skin-eyes-mouth herpes disease, and lowers the rate of mortality and sequelae when the disease has disseminated and is located in the central nervous system.

PP65 antigenemia in the diagnosis of cytomegalovirus infection in AIDS patients

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RC Capela

2012-01-01

Full Text Available Cytomegalovirus causes significant morbidity and mortality in AIDS patients and those having undergone bone marrow or another transplant. PP65 antigenemia is based on detecting viral antigen in peripheral blood leukocytes through immunochemistry and by monitoring the infection in immunocompromised individuals. The present study aimed to set up this diagnostic technique in AIDS patients with active cytomegalovirus infection and verify its occurrence in the Botucatu region of São Paulo state, Brazil. Fifty patients, 35 men and 15 women aged from 24 to 69 years, were recruited from those attended at the Department of Tropical Diseases of Botucatu Medical School, UNESP, and divided into three groups according to CD4+ T lymphocyte counts and antiretroviral treatment. The control group comprised bone marrow transplant patients. Fourteen AIDS patients with low CD4+ cell counts tested positive for PP65 antigenemia, which could predict cytomegalovirus infection and indicate prophylactic treatment.

Postnatally acquired cytomegalovirus infections in preterm infants

NARCIS (Netherlands)

Nijman, J.

2013-01-01

A postnatal cytomegalovirus (CMV) infection is common in very low birth weight infants with an estimated prevalence of 6–59%. Breast milk from CMV seropositive mothers is the main source of postnatal CMV infection. Ninety-six percent of these mothers shed CMV in their breast milk after delivery due

Cytomegalovirus in inflammatory bowel disease: A systematic review

NARCIS (Netherlands)

Romkens, T.E.; Bulte, G.J.; Nissen, L.H.; Drenth, J.P.

2016-01-01

AIM: To identify definitions of cytomegalovirus (CMV) infection and intestinal disease, in inflammatory bowel disease (IBD), to determine the prevalence associated with these definitions. METHODS: We conducted a systematic review and interrogated PubMed, EMBASE and Cochrane for literature on

Acute hepatitis due to Epstein–Barr virus with cross-reacting antibodies to cytomegalovirus

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Asli Karadeniz

2018-01-01

Full Text Available Epstein–Barr virus (EBV is the cause of systemic infection known as infectious mononucleosis with classic presentation of fever, oropharyngitis and lymphadenitis. EBV rarely causes acute hepatitis. In this report, we present a 19-year-old patient presented with nausea, fatigue and jaundice. Her physical examination and laboratory tests revealed the diagnosis as acute hepatitis due to EBV with cross-reacting antibodies to cytomegalovirus.

Cytomegalovirus infection with lissencephaly

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Joseph Leena

2008-07-01

Full Text Available Lissencephaly is a malformation of the brain in which the brain surface is smooth, rather than convoluted. Among the various causes of lissencephaly, infection by a virus during pregnancy plays an important role. Cytomegalovirus (CMV is an important pathogen causing this anomaly. We present this case of a young female with 24-week-gestation diagnosed on ultrasound as carrying an anomalous fetus with lissencephalic features. At autopsy, there were multiple intra-nuclear CMV inclusions in the brain and the kidneys. This case is presented for its rarity and for the documentation of the tissue localization of CMV inclusions at autopsy.

Immunological targeting of cytomegalovirus for glioblastoma therapy

OpenAIRE

Nair, Smita K; Sampson, John H; Mitchell, Duane A

2014-01-01

Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are capable of recognizing and killing autologous GBM tumor cells. This data supports CMV antigen-directed immunotherapies against GBM.

A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion.

Science.gov (United States)

Patel, Swapneel J; Zhao, Guoyan; Penna, Vinay R; Park, Eugene; Lauron, Elvin J; Harvey, Ian B; Beatty, Wandy L; Plougastel-Douglas, Beatrice; Poursine-Laurent, Jennifer; Fremont, Daved H; Wang, David; Yokoyama, Wayne M

2017-05-01

The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4 + T cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By next-generation sequencing of infected tissue homogenates, we assembled a contiguous 174-kb genome sequence containing 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV-6A, HHV-6B, and HHV-7, than to another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV-6A, HHV-6B, and HHV-7. IMPORTANCE Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesviruses 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and

Cytomegalovirus infection in inflammatory bowel disease is not associated with worsening of intestinal inflammatory activity.

Directory of Open Access Journals (Sweden)

Alexandre Medeiros do Carmo

Full Text Available Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus.Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations.Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient.Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine.The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel

Hygiene interventions for prevention of cytomegalovirus infection among childbearing women: systematic review.

Science.gov (United States)

Harvey, Jessica; Dennis, Cindy-Lee

2008-09-01

This paper is a report of a systematic review to examine the effectiveness of preventive interventions to reduce congenital cytomegalovirus transmission and infection among women of childbearing age. Congenital cytomegalovirus has been identified as the leading infectious cause of damage to the growing fetus in developed countries, including Down syndrome, fetal alcohol syndrome and spina bifida. Despite the prevalence and consequences of this infection, it has a low profile and pregnant mothers are often unaware of the risks and protective behaviours related to its transmission. Women with children in daycare and nurses working with children are particularly at risk of acquiring the virus. A computerized literature search for articles up to 1 December 2007 was performed using MEDLINE (from 1950); EMBASE (from 1980) and CINAHL (from 1982). Both authors independently reviewed studies that met inclusion criteria and assigned a quality rating determined by the number of validity criteria met. Differences were discussed until consensus was reached. Differences in hygiene behaviour changes were most statistically significant for pregnant, seronegative women. Although the methodological quality of the three included studies was not strong, seroconversion rates consistently decreased as cytomegalovirus education and support increased. Nurses can act as preventive agents for cytomegalovirus infection through education about hygiene precautions during antenatal care and through preventive measures in the workplace. The review findings suggest educational interventions in hygiene practices have the potential to be a feasible, large-scale, primary prevention strategy.

Incidence and risk of primary cytomegalovirus infection among ...

African Journals Online (AJOL)

Background: Primary cytomegalovirus infection in pregnancy remains a leading cause of congenital hearing loss and mental retardation worldwide. Most women acquired CMV infection horizontally from their infected children or younger children who were cross- infected at school or day care facilities. Over 90% of infected ...

Successful treatment of Cytomegalovirus (CMV) pneumonitis with a ...

African Journals Online (AJOL)

Cytomegalovirus (CMV) is a double-stranded DNA virus, the largest in the Herpesvirus family. CMV disease in adults usually arises from reactivation of latent infection acquired in childhood, individuals with impaired cell mediated immunity are at risk: organ transplant recipients, individuals on chemotherapy or other ...

Cytomegalovirus antibodies among healthy blood donors at Lagos ...

African Journals Online (AJOL)

Objectives. Cytomegalovirus (CMV) is found worldwide in all geographical locations and socio-economic groups and is the virus most frequently transmitted to a developing child before birth. This study aimed to determine the prevalence and risk factors for CMV antibodies among healthy blood donors at Lagos University ...

Pathogenesis of Candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.

Directory of Open Access Journals (Sweden)

Ilse D Jacobsen

Full Text Available Alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. In this study, we investigated the pathogenesis of Candida albicans and C. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (CAM and analyzed the virulence of deletion mutants. The developing immune system of the host significantly influenced susceptibility: With increasing age, embryos became more resistant and mounted a more balanced immune response, characterized by lower induction of proinflammatory cytokines and increased transcription of regulatory cytokines, suggesting that immunopathology contributes to pathogenesis. While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos. IL-22 and IL-17A were only upregulated after the peak mortality in the chicken embryo model occurred; thus, the role of the Th17 response in this model remains unclear. Abscess formation occurs frequently in murine models, whereas the avian response was dominated by granuloma formation. Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines. However, fungal burden did not correlate with virulence and for few mutants like bcr1Δ and tec1Δ different outcomes in survival compared to murine infections were observed. C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections. These data suggest that the pathogenesis of C. albicans infections in the chicken embryo model resembles systemic murine infections but also differs in some aspects. Despite

Childhood environments and cytomegalovirus serostatus and reactivation in adults

NARCIS (Netherlands)

Janicki-Deverts, D.; Cohen, S.; Doyle, W.J.; Marsland, A.L.; Bosch, J.

2014-01-01

Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different

Current strategies and future directions for the prevention of transfusion-transmitted cytomegalovirus

Directory of Open Access Journals (Sweden)

Harmon CM

2017-04-01

Full Text Available Charles M Harmon, Laura L Cooling Department of Pathology, University of Michigan, Ann Arbor, MI, USA Abstract: Cytomegalovirus (CMV is a pervasive DNA virus that infects a significant portion of individuals worldwide, and may be transmitted through the transfusion of blood products. Although CMV infection is of little consequence in immunocompetent individuals, patients with an impaired immune system are at risk of significant morbidity and mortality. Unlike other blood-borne infectious agents, it is impractical to defer all CMV-positive individuals from blood donation as this would exclude a substantial number of otherwise eligible donors. Other methods such as transfusion of CMV-seronegative and leukoreduced blood products must be employed to prevent the transmission of CMV to at-risk patients. In this study, the widespread use of current strategies for the prevention of transfusion-transmitted CMV (TT-CMV infection and the evidence to support these methods in various at-risk groups were reviewed. In addition, emerging pathogen inactivation technologies that have the potential to eliminate TT-CMV were also discussed. Keywords: blood transfusion, cytomegalovirus, leukoreduction, pathogen inactivation, hematopoietic stem cell transplantation, very low birth weight infants

Early-life environment influencing susceptibility to cytomegalovirus infection

DEFF Research Database (Denmark)

Mortensen, Laust Hvas; Maier, A B; Slagbom, P E

2012-01-01

Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two...... number for partners was 71% (Psusceptibility to CMV infection...

Sero-Prevalence of Cytomegalovirus Infection among New -Born ...

African Journals Online (AJOL)

Aim: The aim of this study was to determine the seroprevalence of cytomegalovirus (CMV) infection in newborn babies in our environment and hence the suitability of cord blood for stem cell transplantation. Methodology: Cord blood sera of 212 babies in the labour room of the University of Benin Teaching Hospital (UBTH) ...

Molecular diagnostic of cytomegalovirus, Epstein Barr virus and ...

African Journals Online (AJOL)

Introduction: in most developing countries, Cytomegalovirus (CMV), Epstein Barr virus (EBV) and Herpes virus 6 (HHV-6) are not diagnosed in blood donors. The aim of this study is to determine the prevalence of these viruses in blood donors from the city of Ouagadougou, Burkina Faso. Methods: the study included 198 ...

Epstein-Barr Virus and Cytomegalovirus induced Acute Hepatitis in Young Female Patient.

Science.gov (United States)

Ates, İhsan; Kaplan, Mustafa; Yilmaz, Nisbet; Çiftçi, Filiz

2015-01-01

Acute hepatitis is a disorder that goes with liver cell necrosis and liver inflammation. Among the causes of acute hepatitis, the most common reasons are viral hepatitis. About 95% of the acute hepatitis generate because of hepatotropic viruses. Epstein-barr virus (EBV) and cytomegalovirus (CMV) are from the family of herpes viruses and rare causes of acute hepatitis. In this case report, acute hepatitis due to EBV and CMV coinfection will be described. Ates İ, Kaplan M, Yilmaz N, Çiftçi F. Epstein-Barr Virus and Cytomegalovirus induced Acute Hepatitis in Young Female Patient. Euroasian J Hepato-Gastroenterol 2015;5(1):60-61.

Cytomegalovirus as a cause of anterior uveitis in immunocompetent patients

NARCIS (Netherlands)

van Boxtel, Lonneke A. A.; van der Lelij, Allegonda; van der Meer, Johannes; Los, Leonoor I.

Purpose: To describe 7 cases of unilateral, chronic and/or recurrent anterior uveitis caused by cytomegalovirus (CMV) in immunocompetent patients; to identify specific ophthalmologic characteristics; and to evaluate the clinical effect of valganciclovir treatment. Design: Retrospective observational

Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

DEFF Research Database (Denmark)

Grønborg, Helene Ladefoged; Jespersen, Sanne; Hønge, Bo Langhoff

2016-01-01

reported CMV manifestations in HIV‐infected individuals. Among patients with pulmonary symptoms, the prevalence of CMV pneumonitis varied from 20% to over 60%, whereas CMV was found in 0% to 14% of patients with gastrointestinal manifestations. Cytomegalovirus retinitis was found in 0% to 2.6% of examined......Background: Cytomegalovirus (CMV) infection among HIV‐infected individuals may cause end‐organ disease, which is an AIDS‐defining condition. Evidence from high‐income countries suggests that CMV may alter the outcome of HIV infection, other than causing end‐organ diseases. We reviewed literature...... on HIV and CMV coinfection in Africa. Methods: Systematic review of published studies on HIV and CMV coinfection in Africa using the PubMed database. Results: High CMV seroprevalence was found throughout Africa, exceeding 90% in most populations. Retinitis, pneumonia, and colitis were the most commonly...

Cytomegalovirus-Induced Effector T Cells Cause Endothelial Cell Damage

NARCIS (Netherlands)

van de Berg, Pablo J. E. J.; Yong, Si-La; Remmerswaal, Ester B. M.; van Lier, René A. W.; ten Berge, Ineke J. M.

2012-01-01

Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases that involve vascular endothelial cell damage, but definitive proof for a direct cytopathic effect of CMV in these diseases is lacking. CMV infection is associated with a strong increase in both CD4(+) and CD8(+) T cells

Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

Science.gov (United States)

Ruiz-Cruz, Matilde; Alvarado-de la Barrera, Claudia; Ablanedo-Terrazas, Yuria; Reyes-Terán, Gustavo

2014-07-15

Cytomegalovirus (CMV) retinitis has been extensively described in patients with advanced or late human immunodeficiency virus (HIV) disease under ineffective treatment of opportunistic infection and antiretroviral therapy (ART) failure. However, there is limited information about patients who develop active cytomegalovirus retinitis as an immune reconstitution inflammatory syndrome (IRIS) after successful initiation of ART. Therefore, a case definition of cytomegalovirus-immune recovery retinitis (CMV-IRR) is proposed here. We reviewed medical records of 116 HIV-infected patients with CMV retinitis attending our institution during January 2003-June 2012. We retrospectively studied HIV-infected patients who had CMV retinitis on ART initiation or during the subsequent 6 months. Clinical and immunological characteristics of patients with active CMV retinitis were described. Of the 75 patients under successful ART included in the study, 20 had improvement of CMV retinitis. The remaining 55 patients experienced CMV-IRR; 35 of those developed CMV-IRR after ART initiation (unmasking CMV-IRR) and 20 experienced paradoxical clinical worsening of retinitis (paradoxical CMV-IRR). Nineteen patients with CMV-IRR had a CD4 count of ≥50 cells/µL. Six patients with CMV-IRR subsequently developed immune recovery uveitis. There is no case definition for CMV-IRR, although this condition is likely to occur after successful initiation of ART, even in patients with high CD4 T-cell counts. By consequence, we propose the case definitions for paradoxical and unmasking CMV-IRR. We recommend close follow-up of HIV-infected patients following ART initiation. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Host protein Snapin interacts with human cytomegalovirus pUL130 ...

Indian Academy of Sciences (India)

2016-04-07

Apr 7, 2016 ... The interplay between the host and Human cytomegalovirus (HCMV) plays a pivotal role in the outcome of an infection. ... ed from infected cells but is incorporated into the virion envelope in a ..... Fields virology 5th ed.

Cytomegalovirus Survival and Transferability and the Effectiveness of Common Hand-Washing Agents against Cytomegalovirus on Live Human Hands

OpenAIRE

Stowell, Jennifer D.; Forlin-Passoni, Daniela; Radford, Kay; Bate, Sheri L.; Dollard, Sheila C.; Bialek, Stephanie R.; Cannon, Michael J.; Schmid, D. Scott

2014-01-01

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 105 infectious particles/ml. Samples fr...

Cytomegalovirus (CMV) research in immune senescence comes of age: overview of the 6th International Workshop on CMV and Immunosenescence

NARCIS (Netherlands)

Nikolich-Žugich, Janko; van Lier, René A. W.

2017-01-01

Cytomegalovirus (CMV) is one of the most complex and most ubiquitous latent persistent viruses, with a considerable ability to evade and manipulate the immune system. Following an early-life infection, most immunocompetent humans spend several decades living with CMV, and, because the virus in these

Detection of Cytomegalovirus DNA in Serum Correlates with Clinical Cytomegalovirus Retinitis in AIDS

DEFF Research Database (Denmark)

Hansen, K.K.; Ricksten, A.; Hofmann, B.

1994-01-01

The high sensitivity of nested polymerase chain reaction (PCR) offers the possibility of rapid detection of cytomegalovirus (CMV) DNA in serum. Five consecutive serum samples were examined from 52 human immunodeficiency virus (HIV)-seropositive patients (19 of whom had clinically presumed diagnosis...... became positive with the onset of clinical retinitis. In contrast, 29 of 33 HIV-seropositive subjects without clinical CMV chorioretinitis and matched with respect to age and CD4 T cell numbers were negative for CMV DNA in all 5 serum samples. Thus, the presence of CMV DNA in serum analyzed by PCR...... is a good predictive marker of CMV retinitis in HIV-seropositive subjects. A positive PCR results supports the clinical diagnosis and may be useful for monitoring response to antiviral treatment....

Biliary scintigraphy in neonatal cytomegalovirus cholestasis

International Nuclear Information System (INIS)

Tadzher, I.S.; Grujovska, S.; Todorovski, G.; Josifovska, T.; Arsovska, S.

1996-01-01

Diagnostic value of hepatobiliary scintigraphy using mebrofenin-Te-99m was assessed in three newborns with cytomegalovirus (CMV) hepatitis and one baby with hepatitis B jaundice. All cases were affected by persistent jaundice with predominately conjugated bilirubin, alcoholic stools, anemia. One of this newborns (case number 1) was suspected of having biliary atresia due to the absence of intestinal excretion of the tracer. After three weeks intestinal passage was seen in scintiscan late after 24 h. Hepatobiliary scintigraphy represents a non-invasive diagnostic procedure which enables the detection of permeability of the biliary tract. (Author)

Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

Directory of Open Access Journals (Sweden)

Scott H Robbins

2007-08-01

Full Text Available Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs for cytokine production, preserves the conventional dendritic cell (cDC compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate

Cytomegalovirus prevalence and transmission after islet allograft transplant in patients with type 1 diabetes mellitus.

Science.gov (United States)

Hafiz, Muhammad M; Poggioli, Raffaella; Caulfield, Aileen; Messinger, Shari; Geiger, Milene C; Baidal, David A; Froud, Tatiana; Ferreira, Jacqueline V; Tzakis, Andreas G; Ricordi, Camillo; Alejandro, Rodolfo

2004-10-01

Cytomegalovirus (CMV) serological status of transplant donors and recipients has important implications on antiviral prophylaxis, morbidity/mortality, donor selection and hospital stay. We evaluated CMV prevalence in our islet transplant candidates (ITC) in comparison with organ donors. We correlated the CMV serological status of our ITC with serology for Epstein-Barr virus and Parvovirus B19, auto-antibodies, patient's age, age at DM onset, duration of DM, gender, race, ABO group, HLA haplotype and C-peptide levels. Cytomegalovirus transmission after islet transplant using the Edmonton regimen was also evaluated. Cytomegalovirus seropositivity varied according to patient group, age, gender and race. Type 1 DM patients had reduced odds of CMV seropositivity when compared with organ donors. In all groups studied, older patients, females, and non-Caucasians were more likely to be CMV seropositive. In addition, no CMV reactivation, infection or disease was observed among our transplanted patients using this steroid-free regimen even after donor/recipient CMV mismatch.

Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival

NARCIS (Netherlands)

Smelt, M. J.; Faas, M. M.; Melgert, B. N.; de Vos, P.; de Haan, Bart; de Haan, Aalzen

2011-01-01

Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats

A microculture system for the measurement of antigen-induced murine lymphocyte proliferation: advantages of 5% horse serum and 5 X 10(-5) M mercaptoethanol.

Science.gov (United States)

Brummer, E; Vris, T W; Lawrence, H S

1977-01-01

Short term microculture systems which measure murine lymphocyte proliferative responses to mitogens are well established. We demonstrate here that these microculture methods are not suitable for antigen-induced responses because of the high levels of murine lymphocyte proliferation in control cultures associated with the use of fetal calf serum or human serum. We also show that this problem can be eliminated with the use of a combination of 5% horse serum and 5 X 10(-5) M mercaptoethanol. We describe an antigen-induced murine lymphocyte proliferation microculture system in which good stimulation indices are achieved and the lymphocyte proliferation in control cultures remain at a low level throughout the 7 day culture period.

Cytomegalovirus immune evasion of myeloid lineage cells.

Science.gov (United States)

Brinkmann, Melanie M; Dağ, Franziska; Hengel, Hartmut; Messerle, Martin; Kalinke, Ulrich; Čičin-Šain, Luka

2015-06-01

Cytomegalovirus (CMV) evades the immune system in many different ways, allowing the virus to grow and its progeny to spread in the face of an adverse environment. Mounting evidence about the antiviral role of myeloid immune cells has prompted the research of CMV immune evasion mechanisms targeting these cells. Several cells of the myeloid lineage, such as monocytes, dendritic cells and macrophages, play a role in viral control, but are also permissive for CMV and are naturally infected by it. Therefore, CMV evasion of myeloid cells involves mechanisms that qualitatively differ from the evasion of non-CMV-permissive immune cells of the lymphoid lineage. The evasion of myeloid cells includes effects in cis, where the virus modulates the immune signaling pathways within the infected myeloid cell, and those in trans, where the virus affects somatic cells targeted by cytokines released from myeloid cells. This review presents an overview of CMV strategies to modulate and evade the antiviral activity of myeloid cells in cis and in trans.

Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection.

Science.gov (United States)

Kawasaki, Hideya; Kosugi, Isao; Meguro, Shiori; Iwashita, Toshihide

2017-02-01

In humans, the herpes virus family member cytomegalovirus (CMV) is the most prevalent mediator of intrauterine infection-induced congenital defect. Central nervous system (CNS) dysfunction is a distinguishing symptom of CMV infection, and characterized by ventriculoencephalitis and microglial nodular encephalitis. Reports on the initial distribution of CMV particles and its receptors on the blood brain barrier (BBB) are rare. Nevertheless, several factors are suggested to affect CMV etiology. Viral particle size is the primary factor in determining the pattern of CNS infections, followed by the expression of integrin β1 in endothelial cells, pericytes, meninges, choroid plexus, and neural stem progenitor cells (NSPCs), which are the primary targets of CMV infection. After initial infection, CMV disrupts BBB structural integrity to facilitate the spread of viral particles into parenchyma. Then, the initial meningitis and vasculitis eventually reaches NSPC-dense areas such as ventricular zone and subventricular zone, where viral infection inhibits NSPC proliferation and differentiation and results in neuronal cell loss. These cellular events clinically manifest as brain malformations such as a microcephaly. The purpose of this review is to clearly delineate the pathophysiological basis of congenital CNS anomalies caused by CMV. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Tuberculoid leprosy and cytomegalovirus retinitis as immune restoration disease in a patient with AIDS.

Science.gov (United States)

Kumar, Shishir; Ghosh, Manab Kumar; Sarkar, Somenath; Mallik, Sudeshna; Biswas, Pradyot Narayan; Saha, Bibhuti

2012-02-01

Here we report a unique case of tuberculoid leprosy and cytomegalovirus retinitis in a 27-year-old female patient with AIDS, suggestive of highly active antiretroviral therapy (HAART)-induced immune restoration disease. After initiation of HAART, the patient presented with decreased visual acuity, hypoesthetic patch with local nerve thickening, and an increase in her CD4+ T cell count. On further investigations cytomegalovirus retinitis and tuberculoid leprosy were confirmed. To our knowledge no case with such a co-existence has previously been reported. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Therapy for cytomegalovirus polyradiculomyelitis in patients with AIDS: treatment with ganciclovir

NARCIS (Netherlands)

de Gans, J.; Portegies, P.; Tiessens, G.; Troost, D.; Danner, S. A.; Lange, J. M.

1990-01-01

Six AIDS patients with progressive cytomegalovirus (CMV) polyradiculomyelitis were treated with ganciclovir in an open study. The diagnosis was based on the presence of a distinct clinical syndrome with progressive flaccid paraparesis, preserved proprioception and urinary retention with specific

Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein

DEFF Research Database (Denmark)

Krishna, B A; Spiess, K; Poole, E L

2017-01-01

Reactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV ...

Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome

NARCIS (Netherlands)

Ong, David S Y; Spitoni, Cristian|info:eu-repo/dai/nl/304625957; Klein Klouwenberg, Peter M C; Verduyn Lunel, Frans M; Frencken, Jos F; Schultz, Marcus J; van der Poll, Tom; Kesecioglu, Jozef; Bonten, Marc J M; Cremer, Olaf L

2015-01-01

PURPOSE: Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate

A Role for Myosin Va in Human Cytomegalovirus Nuclear Egress.

Science.gov (United States)

Wilkie, Adrian R; Sharma, Mayuri; Pesola, Jean M; Ericsson, Maria; Fernandez, Rosio; Coen, Donald M

2018-03-15

Herpesviruses replicate and package their genomes into capsids in replication compartments within the nuclear interior. Capsids then move to the inner nuclear membrane for envelopment and release into the cytoplasm in a process called nuclear egress. We previously found that nuclear F-actin is induced upon infection with the betaherpesvirus human cytomegalovirus (HCMV) and is important for nuclear egress and capsid localization away from replication compartment-like inclusions toward the nuclear rim. Despite these and related findings, it has not been shown that any specific motor protein is involved in herpesvirus nuclear egress. In this study, we have investigated whether the host motor protein, myosin Va, could be fulfilling this role. Using immunofluorescence microscopy and coimmunoprecipitation, we observed associations between a nuclear population of myosin Va and the viral major capsid protein, with both concentrating at the periphery of replication compartments. Immunoelectron microscopy showed that nearly 40% of assembled nuclear capsids associate with myosin Va. We also found that myosin Va and major capsid protein colocalize with nuclear F-actin. Importantly, antagonism of myosin Va with RNA interference or a dominant negative mutant revealed that myosin Va is important for the efficient production of infectious virus, capsid accumulation in the cytoplasm, and capsid localization away from replication compartment-like inclusions toward the nuclear rim. Our results lead us to suggest a working model whereby human cytomegalovirus capsids associate with myosin Va for movement from replication compartments to the nuclear periphery during nuclear egress. IMPORTANCE Little is known regarding how newly assembled and packaged herpesvirus capsids move from the nuclear interior to the periphery during nuclear egress. While it has been proposed that an actomyosin-based mechanism facilitates intranuclear movement of alphaherpesvirus capsids, a functional role for

Congenital cytomegalovirus infection : disease burden and screening tools : towards newborn screening

NARCIS (Netherlands)

Vries, Jutte Jacoba Catharina de

2012-01-01

Cytomegalovirus (CMV) infection is the most common congenital viral infection worldwide. The symptom of congenital CMV infection encountered most frequently is sensorineural hearing loss, which will affect approximately one out of five congenitally infected newborns. Because of the late-onset nature

Bacterial Artificial Chromosome Clones of Viruses Comprising the Towne Cytomegalovirus Vaccine

Directory of Open Access Journals (Sweden)

Xiaohong Cui

2012-01-01

Full Text Available Bacterial artificial chromosome (BAC clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.

Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine.

Science.gov (United States)

Cui, Xiaohong; Adler, Stuart P; Davison, Andrew J; Smith, Larry; Habib, El-Sayed E; McVoy, Michael A

2012-01-01

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.

Congenital and perinatal cytomegalovirus infection

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Chun Soo Kim

2010-01-01

Full Text Available Cytomegalovirus (CMV is currently the most common agent of congenital infection and the leading infectious cause of brain damage and hearing loss in children. Symptomatic congenital CMV infections usually result from maternal primary infection during early pregnancy. One half of symptomatic infants have cytomegalic inclusion disease (CID, which is characterized by involvement of multiple organs, in particular, the reticuloendothelial and central nervous system (CNS. Moreover, such involvement may or may not include ocular and auditory damage. Approximately 90% of infants with congenital infection are asymptomatic at birth. Preterm infants with perinatal CMV infection can have symptomatic diseases such as pneumonia, hepatitis, and thrombocytopenia. Microcephaly and abnormal neuroradiologic imaging are associated with a poor prognosis. Hearing loss may occur in both symptomatic and asymptomatic infants with congenital infection and may progress through childhood. Congenital infection is defined by the isolation of CMV from infants within the first 3 weeks of life. Ganciclovir therapy can be considered for infants with symptomatic congenital CMV infection involving the CNS. Pregnant women of seronegative state should be counseled on the importance of good hand washing and other control measures to prevent CMV infection. Heat treatment of infected breast milk at 72?#608;for 5 seconds can eliminate CMV completely.

Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study.

Science.gov (United States)

Torniainen-Holm, Minna; Suvisaari, Jaana; Lindgren, Maija; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H

2018-03-01

Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults. The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level. Copyright © 2018. Published by Elsevier Inc.

Inflammatory bowel disease after liver transplantation : a role for cytomegalovirus infection

NARCIS (Netherlands)

Verdonk, Robert C; Haagsma, Elizabeth B; Van Den Berg, Aad P; Karrenbeld, Arend; Slooff, Maarten J H; Kleibeuker, Jan H; Dijkstra, Gerard

OBJECTIVE: Despite the use of immunosuppressive drugs, recurrent and de novo inflammatory bowel disease (IBD) can develop after orthotopic liver transplantation (OLT). Cytomegalovirus (CMV) infection has been suggested to play a role in the pathogenesis of IBD. The aim of this study was to

Inflammatory bowel disease after liver transplantation : A role for cytomegalovirus infection

NARCIS (Netherlands)

Verdonk, RC; Haagsma, EB; Van Den Berg, AP; Karrenbeld, A; Slooff, MJH; Kleibeuker, JH; Dijkstra, G

Objective. Despite the use of immunosuppressive drugs, recurrent and de novo inflammatory bowel disease (IBD) can develop after orthotopic liver transplantation (OLT). Cytomegalovirus (CMV) infection has been suggested to play a role in the pathogenesis of IBD. The aim of this study was to

Ecotropic murine leukemia virus-induced fusion of murine cells

International Nuclear Information System (INIS)

Pinter, A.; Chen, T.; Lowy, A.; Cortez, N.G.; Silagi, S.

1986-01-01

Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with [ 3 H]thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells

Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

Science.gov (United States)

Portelli, J; Gordon, A; May, J T

1998-11-01

The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

Partial functional complementation between human and mouse cytomegalovirus chemokine receptor homologues

DEFF Research Database (Denmark)

Farrell, Helen E; Abraham, Alexander M; Cardin, Rhonda D

2011-01-01

The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33-m...

Serial passaging of Candida albicans in systemic murine infection suggests that the wild type strain SC5314 is well adapted to the murine kidney.

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Anja Lüttich

Full Text Available The opportunistic fungal pathogen Candida albicans has a remarkable ability to adapt to unfavorable environments by different mechanisms, including microevolution. For example, a previous study has shown that passaging through the murine spleen can cause new phenotypic characteristics. Since the murine kidney is the main target organ in murine Candida sepsis and infection of the spleen differs from the kidney in several aspects, we tested whether C. albicans SC5314 could evolve to further adapt to infection and persistence within the kidney. Therefore, we performed a long-term serial passage experiment through the murine kidney of using a low infectious dose. We found that the overall virulence of the commonly used wild type strain SC5314 did not change after eight passages and that the isolated pools showed only very moderate changes of phenotypic traits on the population level. Nevertheless, the last passage showed a higher phenotypic variability and a few individual strains exhibited phenotypic alterations suggesting that microevolution has occurred. However, the majority of the tested single strains were phenotypically indistinguishable from SC5314. Thus, our findings indicate that characteristics of SC5314 which are important to establish and maintain kidney infection over a prolonged time are already well developed.

Increased carotid intima-media thickness associated with antibody responses to varicella-zoster virus and cytomegalovirus in HIV-infected patients.

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Mar Masiá

Full Text Available OBJECTIVE: We investigated the relationship of the Herpesviridiae with inflammation and subclinical atherosclerosis in HIV-infected patients. METHODS: Prospective study including virologically suppressed HIV-infected patients. IgG antibodies against herpesviruses, carotid intima-media thickness (cIMT, endothelial function through flow-mediated dilatation (FMD of the brachial artery, and blood atherosclerosis biomarkers (hsCRP, TNF-α, IL-6, MCP-1, MDA, sCD14, sCD163, VCAM-1, ICAM-1, D-dimer, and PAI-1 were measured. RESULTS: 136 patients with HIV viral load <200 copies/ml were included. 93.4% patients were infected with herpes simplex virus type-1, 55.9% with herpes simplex virus type-2, 97.1% with varicella-zoster virus, 65.4% with human herpesvirus-6, 91.2% with cytomegalovirus, and 99.3% with Epstein-Barr virus. Previous AIDS diagnosis was associated with higher cytomegalovirus IgG titers (23,000 vs 17,000 AU, P = 0.011 and higher varicella-zoster virus IgG titers (3.19 vs 2.88 AU, P = 0.047, and there was a positive correlation of the Framingham risk score with IgG levels against cytomegalovirus (Spearman's Rho 0.216, P = 0.016 and Herpes simplex virus-2 (Spearman's Rho 0.293, P = 0.001. IgG antibodies against cytomegalovirus correlated in adjusted analysis with the cIMT (P = 0.030. High seropositivity for varicella-zoster virus (OR 2.91, 95% CI 1.05-8.01, P = 0.039, and for cytomegalovirus (OR 3.79, 95% CI 1.20-11.97, P = 0.023 were predictors for the highest quartile of the cIMT in adjusted analyses. PAI-1 levels were independently associated with cytomegalovirus IgG titers (P = 0.041, IL-6 and ICAM-1 levels with varicella-zoster virus IgG (P = 0.046 and P = 0.035 respectively, and hsCRP levels with Herpes simplex virus-2 IgG (P = 0.035. CONCLUSION: In virologically suppressed HIV-infected patients, antibody responses against herpesviruses are associated with subclinical atherosclerosis, and with increased inflammation and coagulation

Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

International Nuclear Information System (INIS)

Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

1990-01-01

Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host

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Roubalová Kateřina

2005-07-01

Full Text Available Abstract Background Recently, a negative association between Toxoplasma-infection and novelty seeking was reported. The authors suggested that changes of personality trait were caused by manipulation activity of the parasite, aimed at increasing the probability of transmission of the parasite from an intermediate to a definitive host. They also suggested that low novelty seeking indicated an increased level of the neurotransmitter dopamine in the brain of infected subjects, a phenomenon already observed in experimentally infected rodents. However, the changes in personality can also be just a byproduct of any neurotropic infection. Moreover, the association between a personality trait and the toxoplasmosis can even be caused by an independent correlation of both the probability of Toxoplasma-infection and the personality trait with the third factor, namely with the size of living place of a subject. To test these two alternative hypotheses, we studied the influence of another neurotropic pathogen, the cytomegalovirus, on the personality of infected subjects, and reanalyzed the original data after the effect of the potential confounder, the size of living place, was controlled. Methods In the case-control study, 533 conscripts were tested for toxoplasmosis and presence of anti-cytomegalovirus antibodies and their novelty seeking was examined with Cloninger's TCI questionnaire. Possible association between the two infections and TCI dimensions was analyzed. Results The decrease of novelty seeking is associated also with cytomegalovirus infection. After the size of living place was controlled, the effect of toxoplasmosis on novelty seeking increased. Significant difference in novelty seeking was observed only in the largest city, Prague. Conclusion Toxoplasma and cytomegalovirus probably induce a decrease of novelty seeking. As the cytomegalovirus spreads in population by direct contact (not by predation as with Toxoplasma, the observed changes are

The downmodulation of the foreign body reaction by cytomegalovirus encoded interleukin-10

NARCIS (Netherlands)

van Putten, S. M.; Hennink, W. E.; van Luyna, M. J. A.; Harmsen, M. C.; Wubben, Maike

The foreign body reaction (FBR) is of great importance for the function and turnover of biomaterial scaffolds. The development of biological tools that modulate the FBR will augment scaffold functionality and benefit regenerative medicine. The human cytomegalovirus encodes a functional homolog of

A modified screening system for loss-of-function and dominant negative alleles of essential MCMV genes.

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Madlen Pogoda

Full Text Available Inactivation of gene products by dominant negative mutants is a valuable tool to assign functions to yet uncharacterized proteins, to map protein-protein interactions or to dissect physiological pathways. Detailed functional and structural knowledge about the target protein would allow the construction of inhibitory mutants by targeted mutagenesis. Yet, such data are limited for the majority of viral proteins, so that the target gene needs to be subjected to random mutagenesis to identify suitable mutants. However, for cytomegaloviruses this requires a two-step screening approach, which is time-consuming and labor-intensive. Here, we report the establishment of a high-throughput suitable screening system for the identification of inhibitory alleles of essential genes of the murine cytomegalovirus (MCMV. In this screen, the site-specific recombination of a specifically modified MCMV genome was transferred from the bacterial background to permissive host cells, thereby combining the genetic engineering and the rescue test in one step. Using a reference set of characterized pM53 mutants it was shown that the novel system is applicable to identify non-complementing as well as inhibitory mutants in a high-throughput suitable setup. The new cis-complementation assay was also applied to a basic genetic characterization of pM99, which was identified as essential for MCMV growth. We believe that the here described novel genetic screening approach can be adapted for the genetic characterization of essential genes of any large DNA viruses.

Neck stiffness in Guillaine-Barre syndrome subsequent to cytomegalovirus infection

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İbrahim Etem Pişkin

2011-03-01

Full Text Available Guillain-Barre syndrome is an acute inflammatory demyelinating polyradiculoneuropathy that can be seen at any age. The classic symptoms such as flaccid paralysis and areflexia are not always predominant in children. In this study, we presented a 3-year-old girl with Guillain-Barre syndrome associated with cytomegalovirus infection who referred with showed atypical symptoms including neck stiffness.

Interstitial neumonia and cytomegalovirus: and immunopathological process Neumonía intersticial y citomegalovirus: un proceso inmunopatológico

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Ana Isabel Toro

1995-03-01

Full Text Available

Cytomegalovirus (CMV infection is a frequent cause of morbidity and mortality in immunocompromised individuals. including renal and bone marrow transplant recipients and patients with the acquired immunodeficiency syndrome (AIDS. CMV infection often affects the lung producing a fatal interstitial pneumonitis (IP. The pathogenesis of CMV IP is not well understood, but clinical observations in humans and laboratory studies with murine models, offer possibilities for explaining CMV-induced IP as an immunopathological disease.

La infección activa por Citomegalovirus (CMV es causa frecuente de morbi-mortalidad en individuos inmunocomprometidos, particularmente entre receptores de trasplante renal y médula ósea y en personas afectadas por el virus de la inmunodeficiencia adquirida (HIV, en las cuales, a menudo, se presenta neumonía intersticial (NI fatal (1,2. La patogénesis de la NI causada por CMV no es clara aún, pero las observaciones clínicas en el hombre y los estudios con modelos murinos permiten pensar en ella como una alteración inmunopatológica. El análisis de tales conceptos es el objetivo de esta revisión.

Symptomatic Congenital Cytomegalovirus Infection in Children of Seropositive Women

OpenAIRE

Ines Mack; Marie-Anne Burckhardt; Marie-Anne Burckhardt; Ulrich Heininger; Friederike Prüfer; Sven Schulzke; Sven Wellmann

2017-01-01

Cytomegalovirus (CMV) is the most frequent congenital virus infection worldwide. The risk of congenital CMV (cCMV) transmission is highest in seronegative women who acquire primary CMV infection during pregnancy. A growing body of evidence indicates that secondary CMV infections in pregnant women with preconceptual immunity (either through reactivation of latent virus or re-infection with a new strain of CMV) contribute to a much greater proportion of symptomatic cCMV than was previously thou...

A macrophage inflammatory protein homolog encoded by guinea pig cytomegalovirus signals via CC chemokine receptor 1

International Nuclear Information System (INIS)

Penfold, Mark; Miao Zhenhua; Wang Yu; Haggerty, Shannon; Schleiss, Mark R.

2003-01-01

Cytomegaloviruses encode homologs of cellular immune effector proteins, including chemokines (CKs) and CK receptor-like G protein-coupled receptors (GPCRs). Sequence of the guinea pig cytomegalovirus (GPCMV) genome identified an open reading frame (ORF) which predicted a 101 amino acid (aa) protein with homology to the macrophage inflammatory protein (MIP) subfamily of CC (β) CKs, designated GPCMV-MIP. To assess functionality of this CK, recombinant GPCMV-MIP was expressed in HEK293 cells and assayed for its ability to bind to and functionally interact with a variety of GPCRs. Specific signaling was observed with the hCCR1 receptor, which could be blocked with hMIP -1α in competition experiments. Migration assays revealed that GPCMV-MIP was able to induce chemotaxis in hCCR1-L1.2 cells. Antisera raised against a GST-MIP fusion protein immunoprecipitated species of ∼12 and 10 kDa from GPCMV-inoculated tissue culture lysates, and convalescent antiserum from GPCMV-infected animals was immunoreactive with GST-MIP by ELISA assay. These results represent the first substantive in vitro characterization of a functional CC CK encoded by a cytomegalovirus

Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia

DEFF Research Database (Denmark)

Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik

2018-01-01

BACKGROUND: The diagnostic yield for cytomegalovirus (CMV) PCR viral load in Bronchoalveolar Lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain, and was investigated in a large cohort of consecutive lung transplant recipients. METHODS: Bronchoscopi...

Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis.

Science.gov (United States)

Kim, Tae-Seok; Ahn, Keun Soo; Kim, Yong Hoon; Kim, Hyoung Tae; Jang, Byoung Kuk; Hwang, Jae Seok; Kim, Il-Man; Kang, Yu Na; Kang, Koo Jeong

2017-02-01

Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.

Child Care Provider Awareness and Prevention of Cytomegalovirus and Other Infectious Diseases

Science.gov (United States)

Thackeray, Rosemary; Magnusson, Brianna M.

2016-01-01

Background: Child care facilities are prime locations for the transmission of infectious and communicable diseases. Children and child care providers are at high risk for cytomegalovirus (CMV) infection which causes severe birth defects and developmental delays. Objective: The goals of study were: (1) to determine the level of cytomegalovirus…

Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models

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Mao-Qiang Man

2012-01-01

Full Text Available Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA, respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.

Cytomegalovirus pneumonitis complicated by a central peribronchial pattern of organising pneumonia.

Science.gov (United States)

Cuadrado, Maria M; Ahmed, Asia; Carpenter, Ben; Brown, Jeremy S

2017-01-01

We present five cases of cytomegalovirus (CMV) pneumonitis occurring in patients after recent T cell deplete allogeneic stem cell transplantation (AlloHSCT). These cases were complicated by an organising pneumonia (during the recovery period) with a predominantly central peribronchial pattern. All patients presented with evidence of active CMV pneumonitis which was treated successfully with anti-viral therapy but was followed by persistent severe dyspnoea, cough and hypoxia. High resolution computed tomography (HRCT) imaging showed widespread central peribronchial consolidation with traction bronchiectasis. There was a marked clinical and physiological improvement after treatment with systemic corticosteroids. However, in all patients the lung function remained abnormal and in some cases imaging revealed a fibrosing lung disease. These cases represent a previously undescribed central peribronchial pattern of organising pneumonia complicating CMV pneumonitis that can result in chronic lung damage.

Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

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Amelia Kellar

2015-01-01

Full Text Available Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.

Epstein-Barr virus, cytomegalovirus, and infectious mononucleosis.

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Bravender, Terrill

2010-08-01

Infectious mononucleosis (IM) is a clinical syndrome that is common in adolescents and young adults and is characterized by fever, lymphadenopathy, pharyngitis, and fatigue. IM is most commonly associated with Epstein-Barr virus (EBV) infection in which case laboratory findings include a lymphocytosis with an elevated number of atypical lymphocytes seen on peripheral smear and a heterophile or EBV-specific antibody response. Approximately 10% of those with IM will not be acutely infected with EBV. Many of these individuals will have their symptoms attributed to cytomegalovirus (CMV) infection. This chapter reviews the history, diagnosis, clinical management, and potential complications of both EBV- and CMV-associated IM in adolescents and young adults.

Intelligence and Academic Achievement With Asymptomatic Congenital Cytomegalovirus Infection.

Science.gov (United States)

Lopez, Adriana S; Lanzieri, Tatiana M; Claussen, Angelika H; Vinson, Sherry S; Turcich, Marie R; Iovino, Isabella R; Voigt, Robert G; Caviness, A Chantal; Miller, Jerry A; Williamson, W Daniel; Hales, Craig M; Bialek, Stephanie R; Demmler-Harrison, Gail

2017-11-01

To examine intelligence, language, and academic achievement through 18 years of age among children with congenital cytomegalovirus infection identified through hospital-based newborn screening who were asymptomatic at birth compared with uninfected infants. We used growth curve modeling to analyze trends in IQ (full-scale, verbal, and nonverbal intelligence), receptive and expressive vocabulary, and academic achievement in math and reading. Separate models were fit for each outcome, modeling the change in overall scores with increasing age for patients with normal hearing ( n = 78) or with sensorineural hearing loss (SNHL) diagnosed by 2 years of age ( n = 11) and controls ( n = 40). Patients with SNHL had full-scale intelligence and receptive vocabulary scores that were 7.0 and 13.1 points lower, respectively, compared with controls, but no significant differences were noted in these scores among patients with normal hearing and controls. No significant differences were noted in scores for verbal and nonverbal intelligence, expressive vocabulary, and academic achievement in math and reading among patients with normal hearing or with SNHL and controls. Infants with asymptomatic congenital cytomegalovirus infection identified through newborn screening with normal hearing by age 2 years do not appear to have differences in IQ, vocabulary or academic achievement scores during childhood, or adolescence compared with uninfected children. Copyright © 2017 by the American Academy of Pediatrics.

RATIONALE FOR A SPECIFIC THERAPY OF CYTOMEGALOVIRUS INFECTION IN CHILDREN WITH BRONCHIAL ASTHMA

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E. N. Suprun

2013-01-01

Full Text Available Abstract. We propose a protocol of treatment in cases of bronchial asthma with cytomegalovirus (CMV persistence. This basic therapy is administered depending on the disease severity, according to the National Programme 2009. The treatment includes administration of human immunoglobulin, with dosage according on CMV antibodies titers. The study has revealed that such regimen of antibody administration based on the content of anti-CMV antibodies in bronchial asthma treatment stops active CMV replication in bronchial mucous membrane, alleviates clinical course of the disease, diminishes changes of immune system typical to children suffering from bronchial asthma and CMV reactivation, thus allowing to reduce the volume of basic therapy, along with maintaining control of asthma control.

Peripheral Blood Leukocytes and Serum Nested Polymerase Chain Reaction Are Complementary Methods for Monitoring Active Cytomegalovirus Infection in Transplant Patients

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PD Andrade

2013-01-01

Full Text Available BACKGROUND: Human cytomegalovirus is an important cause of morbidity and mortality in immunocompromised patients. Qualitative polymerase chain reaction (PCR has proven to be a sensitive and effective technique in defining active cytomegalovirus infection, in addition to having low cost and being a useful test for situations in which there is no need for quantification. Real-time PCR has the advantage of quantification; however, the high cost of this methodology makes it impractical for routine use.

Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease.

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Dallar, Yildiz; Tiras, Ulku; Catakli, Tulin; Gulal, Gonul; Sayar, Yavuz; Selvar, Beray; Alioglu, Bulent

2011-02-01

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.

Analysis of cardiomyocyte movement in the developing murine heart

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Hashimoto, Hisayuki [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Tabata, Hidenori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Nakajima, Kazunori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Sakaue-Sawano, Asako; Miyawaki, Atsushi [Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Fukuda, Keiichi [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan)

2015-09-04

The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

Congenital Cytomegalovirus Infection: Child Development, Quality of Life and Impact on Daily Life.

NARCIS (Netherlands)

Korndewal, Marjolein J; Oudesluys-Murphy, Anne Marie; Kroes, Aloys C M; Vossen, Ann C T M; de Melker, Hester E

2017-01-01

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection worldwide and can lead to long-term impairments such as developmental delay. It is currently unknown how this affects the daily life of children and their parents. Children For this study, children with cCMV were

Cytomegalovirus Disease in Renal Transplant Recipients: A Single-Center Experience

OpenAIRE

Bhadauria, Dharmendra; Sharma, R. K.; Kaul, A.; Prasad, Narayan; Gupta, Amit; Gupta, Anurag; Srivastava, Aneesh

2012-01-01

Cytomegalovirus (CMV) is the most common viral infection following kidney transplant, has been recognized as a major factor for graft loss and increased incidence of acute rejection. Different studies have reported a variable incidence of CMV disease with the use of Mycophenolate mofetil (MMF). We retrospectively analyzed our renal transplant recipients to review the results of CMV disease and to compare CMV disease in patient on Azathioprine and MMF for this purpose we retrospectively review...

Citomegalovirose congênita: relato de caso Congenital cytomegalovirus infection: a case report

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Patrícia de Fátima Azevedo

2005-12-01

Full Text Available A citomegalovirose congênita sintomática é entidade clínica de grande importância devido a sua vasta sintomatologia fetal. No Brasil, o diagnóstico intra-útero é ainda pouco realizado, apesar do grande arsenal propedêutico. Relatamos um caso de citomegalovirose congênita grave com hepatoesplenomegalia, agenesia parcial do vérmix cerebelar, calcificações intracranianas, placentomegalia, aumento da ecogenicidade intestinal e renal, cardiomegalia, hipoplasia pulmonar, derrame pericárdico e ascite. A ressonância nuclear magnética fetal foi utilizada para confirmação dos achados ultra-sonográficos. A amniocentese foi realizada para análise do líquido amniótico por meio da PCR, sendo evidenciado resultado positivo. O óbito fetal foi constatado na 31ª semana de gestação, sendo confirmados os achados através da citopatologia e estudo anatomopatológico do natimorto. O arsenal propedêutico existente, na atualidade, para diagnóstico intra-útero da citomegalovirose congênita é de grande importância para confirmação diagnóstica e determinação do prognóstico fetal.Congenital cytomegalovirus infection is an important clinical entity, due to its sonographic symptomatology. In Brazil, in utero diagnosis is not accomplished despite the improvements in diagnostic methods. We report a congenital infection including: splenomegaly and hepatomegaly, hypoplasia of the cerebellar vermis, intracranial calcifications, hyperechoic kidneys, hyperechoic bowel, cardiomegaly, lung hypoplasia, ascites, and pericardial effusion. Fetal magnetic resonance imaging confirmed the sonographic findings. Amniocentesis was performed for cytomegalovirus PCR in amniotic fluid, which confirmed fetal infection. Fetal loss occurred in the 31st week of pregnancy. Necropsy studies confirmed the sonographic findings. The diagnostic methods have been useful to confirm congenital cytomegalovirus infection and to establish fetal outcome.

Dataset of aqueous humor cytokine profile in HIV patients with Cytomegalovirus (CMV retinitis

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Jayant Venkatramani Iyer

2016-09-01

Full Text Available The data shows the aqueous humor cytokine profiling results acquired in a small cohort of 17 HIV patients clinically diagnosed with Cytomegalovirus retinitis using the FlexMAP 3D (Luminex® platform using the Milliplex Human Cytokine® kit. Aqueous humor samples were collected from these patients at different time points (pre-treatment and at 4-weekly intervals through the 12-week course of intravitreal ganciclovir treatment and 41 cytokine levels were analyzed at each time point. CMV DNA viral load was assessed in 8 patients at different time points throughout the course of ganciclovir treatment. The data described herein is related to the research article entitled “Aqueous humor immune factors and cytomegalovirus (CMV levels in CMV retinitis through treatment - The CRIGSS study” (Iyer et al., 2016 [1]. Cytokine levels against the different time points which indicate the response to the given treatment and against the CMV viral load were analyzed. Keywords: Cytokines, CMV retinitis, Dataset, HIV, Luminex bead assay

IgM-specific serodiagnosis of acute human cytomegalovirus infection using recombinant autologous fusion proteins

NARCIS (Netherlands)

Vornhagen, R; Hinderer, W; Sonneborn, HH; Bein, G; Matter, L; The, T. Hauw; Enders, G; Jahn, G; Plachter, B

Portions of three human cytomegalovirus (HCMV) polypeptides, which were shown previously to be highly reactive with patient sera, were expressed in Escherichia coli as autologous fusion proteins. Purified recombinant polypeptides were used as antigens in enzyme linked immunosorbent assay (ELISA) and

Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

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Fatehi Elnour Elzein

2016-01-01

Full Text Available The mortality in Strongyloides hyperinfection syndrome (SHS is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli urosepsis and CMV infection.

[Redox-potential of blood and consistence of energoproviding defence system in cytomegalovirus infection in pregnancy].

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Dzhikiia, I V; Rizhvadze, M A; Dzhangidze, M A

2006-05-01

We have studied the relationship between the hypoxic change and mitochondrial redox-potential disturbances in the mechanism of pheto-placental insufficiency in pregnancy with cytomegalovirus infection (CMV), detected by the positive anti-CMV-IgG titer and more then 4-fold increase of low avid anti-CMV-IgG. It was shown, that chronic CMV infection induces production of active forms of oxygen, peroxidation of structures and concurrently damage of mitochondria with essential decrease of ATP level. Results of the study have shown the important diagnostic value of estimation of hypoxic-oxidative damage induced by CMV infection. The results also revealed important relationships between the activity of the CMV infection and intensity of mitochondrial damage. On the basis of our investigations we suggest the additional diagnostic test (the determination of citozol NADH dependent isocitratdehydrogenaze activity) to evaluate the depth of CMV induced metabolic disturbances.

Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

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Restrepo-Gualteros, Sonia; Jaramillo-Barberi, Lina; Gonzalez-Santos, Monica; Rodriguez-Martinez, Carlos; Perez, Geovanny; Gutierrez, Maria; Nino, Gustavo

2014-01-01

Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%...

Murine cytomegalovirus immediate-early 1 gene expression correlates with increased GVHD after allogeneic hematopoietic cell transplantation in recipients reactivating from latent infection.

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Senthilnathan Palaniyandi

Full Text Available The success of allogeneic (allo hematopoietic cell transplantation (HCT is limited by its treatment related complications, mostly graft versus host disease (GVHD and fungal and viral infections. CMV reactivation after HCT has been associated with increased morbidity and mortality, and a causal relation between GVHD, immunosuppressive therapy and vice versa has been postulated. Using a low GVHD severity murine HCT model, we assessed the role of MCMV reactivation and GVHD development. BALB/c mice were infected with either murine CMV (MCMV or mock and monitored for 25 weeks to establish latency, followed by sublethal irradiation conditioning and infusion of bone marrow plus splenocytes from either syngeneic (syn BALB/c or allo B10.D2 donors. Engraftment of allo donor cells was confirmed by PCR for D2Mit265 gene product size. Day+100 mortality and overall GVHD severity in allo MCMV pre-infected recipients was higher than in allo mock controls. Pathologic changes of lung and liver GVHD in immediate-early gene 1 (IE1 positive recipients were significantly increased compared to mock controls, and were only slightly increased in IE1 negative. No significant gut injury was seen in any group. Aggravated lung injury in IE1 positive recipients correlated with higher BAL cell counts both for total cells and for CD4+ T cells when compared with mock controls, and also with protein expression of lung IFN-gamma and liver TNF. No evidence for CMV specific morphologic changes was seen on histopathology in any organ of IE1 positive recipients, suggesting that CMV reactivation is related to increased GVHD severity but does not require active CMV disease, strengthening the concept of a reciprocal relationship between CMV and GVHD.

Automated Nucleic Acid Extraction Systems for Detecting Cytomegalovirus and Epstein-Barr Virus Using Real-Time PCR: A Comparison Study Between the QIAsymphony RGQ and QIAcube Systems.

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Kim, Hanah; Hur, Mina; Kim, Ji Young; Moon, Hee Won; Yun, Yeo Min; Cho, Hyun Chan

2017-03-01

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are increasingly important in immunocompromised patients. Nucleic acid extraction methods could affect the results of viral nucleic acid amplification tests. We compared two automated nucleic acid extraction systems for detecting CMV and EBV using real-time PCR assays. One hundred and fifty-three whole blood (WB) samples were tested for CMV detection, and 117 WB samples were tested for EBV detection. Viral nucleic acid was extracted in parallel by using QIAsymphony RGQ and QIAcube (Qiagen GmbH, Germany), and real-time PCR assays for CMV and EBV were performed with a Rotor-Gene Q real-time PCR cycler (Qiagen). Detection rates for CMV and EBV were compared, and agreements between the two systems were analyzed. The detection rate of CMV and EBV differed significantly between the QIAsymphony RGQ and QIAcube systems (CMV, 59.5% [91/153] vs 43.8% [67/153], P=0.0005; EBV, 59.0% [69/117] vs 42.7% [50/117], P=0.0008). The two systems showed moderate agreement for CMV and EBV detection (kappa=0.43 and 0.52, respectively). QIAsymphony RGQ showed a negligible correlation with QIAcube for quantitative EBV detection. QIAcube exhibited EBV PCR inhibition in 23.9% (28/117) of samples. Automated nucleic acid extraction systems have different performances and significantly affect the detection of viral pathogens. The QIAsymphony RGQ system appears to be superior to the QIAcube system for detecting CMV and EBV. A suitable sample preparation system should be considered for optimized nucleic acid amplification in clinical laboratories.

Cytomegalovirus peritonitis after kidney transplantation diagnosed through histopathological examination.

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Hotta, Kiyohiko; Fukasawa, Yuichiro; Wada, Yoshiki; Fukuzawa, Nobuyuki; Seki, Toshimori; Harada, Hiroshi

2017-08-01

Among organ transplant recipients, cytomegalovirus (CMV) commonly results in various types of infection such as pneumonitis, hepatitis, and enterocolitis. However, CMV peritonitis is very rare and difficult to diagnose owing to lack of visible clinical signs. We present a case of a 35-year-old female kidney recipient who developed abdominal pain and urinary retention caused by CMV peritonitis. To our knowledge, this is the first case report of CMV peritonitis after organ transplantation to be diagnosed through histopathological examination. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human antibody technology and the development of antibodies against cytomegalovirus.

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Ohlin, Mats; Söderberg-Nauclér, Cecilia

2015-10-01

Cytomegalovirus (CMV) is a virus that causes chronic infections in a large set of the population. It may cause severe disease in immunocompromised individuals, is linked to immunosenescence and implied to play an important role in the pathogenesis of cardiovascular diseases and cancer. Modulation of the immune system's abilities to manage the virus represent a highly viable therapeutic option and passive immunotherapy with polyclonal antibody preparations is already in clinical use. Defined monoclonal antibodies offer many advantages over polyclonal antibodies purified from serum. Human CMV-specific monoclonal antibodies have consequently been thoroughly investigated with respect to their potential in the treatment of diseases caused by CMV. Recent advances in human antibody technology have substantially expanded the breadth of antibodies for such applications. This review summarizes the fundamental basis for treating CMV disease by use of antibodies, the basic technologies to be used to develop such antibodies, and relevant human antibody specificities available to target this virus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

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Cheeran, Maxim C.-J.; Lokensgard, James R.; Schleiss, Mark R.

2009-01-01

Congenital cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation and hearing loss in the developed world. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and long-term disabilities associated with CMV infection. In this review, current concepts regarding the pathogenesis of neurological injury caused by CMV infections acquired by the developing fetus are summarized. The pathogenesis of CMV-induced disabilities is con...

Lymphotropic Herpesvirus infection and malignant lymphoma, immunological aspects of cytomegalovirus and Epstein- Barr virus infections

NARCIS (Netherlands)

Napel, Christianus Hubertus Henricus ten

1979-01-01

In de voorgaande hoofdstukken van dit proefschrift werd de oorspronkelijke chronologische volgorde van het onderzoek aangehouden. Maar in dit deel wordt hiervan afgeweken en zullen de resultaten worden samengevat en besproken volgens onderstaande indeling: 1. Cytomegalovirus( CMV)-specifieke

Saturated very long chain fatty acids are required for the production of infectious human cytomegalovirus progeny.

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Emre Koyuncu

Full Text Available Human cytomegalovirus hijacks host cell metabolism, increasing the flux of carbon from glucose to malonyl-CoA, the committed precursor to fatty acid synthesis and elongation. Inhibition of acetyl-CoA carboxylase blocks the production of progeny virus. To probe further the role of fatty acid metabolism during infection, we performed an siRNA screen to identify host cell metabolic enzymes needed for the production of infectious cytomegalovirus progeny. The screen predicted that multiple long chain acyl-CoA synthetases and fatty acid elongases are needed during infection, and the levels of RNAs encoding several of these enzymes were upregulated by the virus. Roles for acyl-CoA synthetases and elongases during infection were confirmed by using small molecule antagonists. Consistent with a role for these enzymes, mass spectrometry-based fatty acid analysis with ¹³C-labeling revealed that malonyl-CoA is consumed by elongases to produce very long chain fatty acids, generating an approximately 8-fold increase in C26-C34 fatty acid tails in infected cells. The virion envelope was yet further enriched in C26-C34 saturated fatty acids, and elongase inhibitors caused the production of virions with lower levels of these fatty acids and markedly reduced infectivity. These results reveal a dependence of cytomegalovirus on very long chain fatty acid metabolism.

Cytomegalovirus infection in the bone marrow transplant patient.

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Bhat, Vivek; Joshi, Amit; Sarode, Rahul; Chavan, Preeti

2015-12-24

Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear.

Congenital Cytomegalovirus Infection: New Prospects for Prevention and Therapy

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Swanson, Elizabeth C.; Schleiss, Mark R.

2013-01-01

SYNOPSIS Cytomegalovirus (CMV) is the most common congenital viral infection in the developed world, with an overall birth prevalence of approximately 0.6%. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have a high risk for demonstration of subsequent neurologic sequelae, including sensorineural hearing loss (SNHL), mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy. Antiviral therapy of children with symptomatic central nervous system (CNS) congenital CMV infection is effective at reducing the risk of long-term disabilities and should be offered to families with affected newborns. An effective pre-conceptual vaccine against CMV could, by preventing congenital infection, protect against long-term neurological sequelae and other disabilities. A variety of active and passive immunization strategies are in clinical trials and are likely to be licensed in the next few years. Until a vaccine is licensed, preventive strategies aimed at reducing transmission should be emphasized and public awareness increased, particularly among women of child-bearing age. PMID:23481104

Cytomegalovirus infection in pregnancy.

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Kagan, Karl Oliver; Hamprecht, Klaus

2017-07-01

Due to the severe risk of long-term sequelae, prenatal cytomegalovirus infection is of particular importance amongst intrauterine viral infections. This review summarizes the current knowledge about CMV infection in pregnancy. A search of the Medline and Embase database was done for articles about CMV infection in pregnany. We performed a detailed review of the literature in view of diagnosis, epidemiology and management of CMV infection in pregnancy. The maternal course of the infection is predominantly asymptomatic; the infection often remains unrecognized until the actual fetal manifestation. Typical ultrasound signs that should arouse suspicion of intrauterine CMV infection can be distinguished into CNS signs such as ventriculomegaly or microcephaly and extracerebral infection signs such as hepatosplenomegaly or hyperechogenic bowel. Current treatment strategies focus on hygienic measures to prevent a maternal CMV infection during pregnancy, on maternal application of hyperimmunoglobulines to avoid materno-fetal transmission in case of a maternal seroconversion, and on an antiviral therapy in case the materno-fetal transmission have occurred. CMV infection in pregnancy may result in a severe developmental disorder of the newborn. This should be taken into account in the treatment of affected and non-affected pregnant women.

Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections

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Lodding, I P; Sengeløv, Henrik; da Cunha-Bang, C

2015-01-01

BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. METHODS: The CMV doubling time of the f...

Relationship between human cytomegalovirus transcription and symptomatic apical periodontitis in Iran.

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Yazdi, K A; Sabeti, M; Jabalameli, F; Eman eini, M; Kolahdouzan, S A; Slots, J

2008-12-01

Apical periodontitis of endodontic origin may develop as a result of cooperative interactions among herpesviruses, specific pathogenic bacteria and tissue-destructive inflammatory mediators. This study sought to identify the presence of Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) transcripts in symptomatic and asymptomatic periapical lesions of individuals living in Iran. Fifty endodontic patients (28 with symptomatic periapical lesions and 22 with asymptomatic periapical lesions) were included in the study. In each study subject, a microbiological periapical sample was collected using a curette in conjunction with periapical surgery. A reverse transcription-polymerase chain reaction assay was used to identify transcripts of EBV and HCMV. Human cytomegalovirus transcript was detected in 15 of the 28 (53.6%) symptomatic and in six of the 22 (27.3%) asymptomatic periapical study lesions (significant difference between symptomatic and asymptomatic lesions; P = 0.03, chi-square test). Epstein-Barr virus transcript was identified in one symptomatic and in two asymptomatic periapical lesions. This study establishes that HCMV transcription is common in apical periodontitis and is most frequent in symptomatic lesions. The high frequency of active herpesvirus infections in severe apical periodontitis changes the pathogenic paradigm of the disease and may also have preventive and therapeutic implications.

Automated Cell Enrichment of Cytomegalovirus-specific T cells for Clinical Applications using the Cytokine-capture System.

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Kumaresan, Pappanaicken; Figliola, Mathew; Moyes, Judy S; Huls, M Helen; Tewari, Priti; Shpall, Elizabeth J; Champlin, Richard; Cooper, Laurence J N

2015-10-05

The adoptive transfer of pathogen-specific T cells can be used to prevent and treat opportunistic infections such as cytomegalovirus (CMV) infection occurring after allogeneic hematopoietic stem-cell transplantation. Viral-specific T cells from allogeneic donors, including third party donors, can be propagated ex vivo in compliance with current good manufacturing practice (cGMP), employing repeated rounds of antigen-driven stimulation to selectively propagate desired T cells. The identification and isolation of antigen-specific T cells can also be undertaken based upon the cytokine capture system of T cells that have been activated to secrete gamma-interferon (IFN-γ). However, widespread human application of the cytokine capture system (CCS) to help restore immunity has been limited as the production process is time-consuming and requires a skilled operator. The development of a second-generation cell enrichment device such as CliniMACS Prodigy now enables investigators to generate viral-specific T cells using an automated, less labor-intensive system. This device separates magnetically labeled cells from unlabeled cells using magnetic activated cell sorting technology to generate clinical-grade products, is engineered as a closed system and can be accessed and operated on the benchtop. We demonstrate the operation of this new automated cell enrichment device to manufacture CMV pp65-specific T cells obtained from a steady-state apheresis product obtained from a CMV seropositive donor. These isolated T cells can then be directly infused into a patient under institutional and federal regulatory supervision. All the bio-processing steps including removal of red blood cells, stimulation of T cells, separation of antigen-specific T cells, purification, and washing are fully automated. Devices such as this raise the possibility that T cells for human application can be manufactured outside of dedicated good manufacturing practice (GMP) facilities and instead be produced

Human cytomegalovirus antigens in malignant gliomas as targets for adoptive cellular therapy

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Daniel eLandi

2014-11-01

Full Text Available Malignant gliomas are the most common primary brain tumor in adults, with over 12,000 new cases diagnosed in the United States each year. Over the last decade, investigators have reliably identified human cytomegalovirus (HCMV proteins, nucleic acids, and virions in most high-grade gliomas, including glioblastoma (GBM. This discovery is significant because human cytomegalovirus gene products can be targeted by immune-based therapies.In this review, we describe the current level of understanding regarding the presence and role in pathogenesis of HCMV in GBM. We describe our success detecting and expanding HCMV-specific cytotoxic T lymphocytes to kill GBM cells and explain how these cells can be used as a platform for enhanced cellular therapies. We discuss alternative approaches that capitalize on HCMV infection to treat patients with HCMV-positive tumors. Adoptive cellular therapy for HCMV-positive GBM has been tried in a small number of patients with some benefit, but we reason why, to date, these approaches generally fail to generate long-term remission or cure. We conjecture how cellular therapy for GBM can be improved and describe the barriers that must be overcome to cure these patients.

Congenital cytomegalovirus infection: disease burden and screening tools : towards newborn screening

OpenAIRE

Vries, Jutte Jacoba Catharina de

2012-01-01

Cytomegalovirus (CMV) infection is the most common congenital viral infection worldwide. The symptom of congenital CMV infection encountered most frequently is sensorineural hearing loss, which will affect approximately one out of five congenitally infected newborns. Because of the late-onset nature of the hearing loss, up to half of the children with congenital CMV-related hearing loss may not be detected in the newborn hearing screening. This thesis addresses several aspects of congenital CM...

The prevalence of human cytomegalovirus DNA in gliomas of Brazilian patients

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Renata Fragelli Fonseca

2012-11-01

Full Text Available Members of the Herpesviridae family have been implicated in a number of tumours in humans. At least 75% of the human population has had contact with cytomegalovirus (HCMV. In this work, we screened 75 Brazilian glioma biopsies for the presence of HCMV DNA sequences. HCMV DNA was detected in 36% (27/75 of the biopsies. It is possible that HCMV could be a co-factor in the evolution of brain tumours.

Prevalence of Cytomegalovirus IgG Antibodies among Pregnant Women Visiting Antenatal Clinic, LAUTECH Teaching Hospital in Osogbo, Osun State, Nigeria.

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Akende, Oluwatosin; Akanbi, Olusola Anuoluwapo; Oluremi, Adeolu Sunday; Okonko, Iheanyi Omezuruike; Opaleye, Oluyinka Oladele

2016-01-01

Cytomegalovirus (CMV) is one of the predominant viral infections that lead to congenital diseases and teratogenic risks during the perinatal stage. There is paucity of seroepidemiological data on anti-CMV IgG antibody in pregnant women in Osogbo, Osun State, Nigeria. This study was aimed at determining the seroprevalence of Cytomegalovirus IgG antibody among pregnant women visiting antenatal clinic, LAUTECH Teaching Hospital, Osogbo, Nigeria. One hundred and seventy-four sera from the pregnant women were screened by Enzyme linked Immunosorbent Assay (ELISA) for cytomegalovirus (CMV) IgG antibody. Data analysis was done using SPSS software. In this study, 105 of the 174 pregnant women were seropositive for CMV IgG antibodies giving an antibody prevalence of 60%. There was no association found between CMV IgG seropositivity and the subjects' demographic characteristics, however, the 60.0% prevalence of CMV-IgG antibody observed amongst pregnant women in this study demands for vaccines and regular testing for the presence of CMV and its related risk factors in antenatal clinic.

Distinctive in vitro effects of T-cell growth cytokines on cytomegalovirus-stimulated T-cell responses of HIV-infected HAART recipients

International Nuclear Information System (INIS)

Patterson, Julie; Jesser, Renee; Weinberg, Adriana

2008-01-01

Functional immune reconstitution is limited after HAART, maintaining the interest in adjunctive immune-modulators. We compared in vitro the effects of the γ-chain T-cell growth cytokines IL-2, IL-4, IL-7 and IL-15 on cytomegalovirus-stimulated cell-mediated immunity. IL-2 and IL-15 increased cytomegalovirus-specific lymphocyte proliferation in HAART recipients, whereas IL-4 and IL-7 did not. The boosting effect of IL-2 and IL-15 on proliferation correlated with their ability to prevent late apoptosis. However, IL-2 increased the frequency of cells in early apoptosis, whereas IL-15 increased the frequency of fully viable cells. Both IL-2 and IL-15 increased cytomegalovirus-induced CD4 + and CD8 + T-cell proliferation and the synthesis of Th1 and pro-inflammatory cytokines and chemokines. However, only IL-2 increased the frequency of regulatory T cells and Th2 cytokine production, both of which have the potential to attenuate antiviral immune responses. Overall, compared to other γ-chain cytokines, IL-15 had the most favorable profile for boosting antiviral cell-mediated immunity

Imported rickettsioses : think of murine typhus

NARCIS (Netherlands)

van der Kleij, FGH; Gansevoort, RT; Kreeftenberg, HG

Murine typhus is a disease still prevalent in many parts of the world. Because the incidence in the US and Europe has declined rapidly, physicians in these continents have become unfamiliar with the clinical picture. Murine typhus is associated with significant morbidity and fatalities do occur,

The time course of development and impact from viral resistance against ganciclovir in cytomegalovirus infection

DEFF Research Database (Denmark)

Cunha-Bang, C da; Kirkby, N; Sønderholm, M

2013-01-01

(Val)ganciclovir is used to treat cytomegalovirus (CMV) infection following solid organ (SOT) or hematopoietic stem cell (HSCT) transplantation. Treatment failures occur, but the contribution from 39 known ganciclovir-related mutations (GRMs) in the CMV-UL97 gene remains controversial. We propose...

Multi-walled carbon nanotubes: biodegradation by gastric agents in vitro and effect on murine intestinal system

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Masyutin, A.; Erokhina, M.; Sychevskaya, K.; Gusev, A.; Vasyukova, I.; Smirnova, E.; Onishchenko, G.

2015-11-01

One of the main questions limiting application of fibrous carbon nanomaterials (CNM) in medicine and food industry concerns presumptive degradation of CNM in living organisms. In this study, we have investigated biodegradation of multi-walled carbon nanotubes (MWCNTs) by gastric agents in vitro and influence of ingested MWCNTs on murine intestine. Using scanning, conventional transmission and analytical electron microscopy, we demonstrated that industrial MWCNTs treated in vitro by 0.1 M hydrochloric acid (pH=1) and gastric juice (pH=2-3) isolated from murine stomach, are subjected to incomplete degradation. After 30 days of oral administration to experimental mice, we did find MWCNTs in the cells of small intestine, and it may indicate that agglomerates of MWCNTs do not penetrate into colon epithelia and do not accumulate in enterocytes. However, we observed local areas of necrotic damages of intestinal villi. It seems likely, therefore, that MWCNTs end up leaving gastrointestinal tract by excretion with the feces. Our results suggest that MWCNTs do not undergo complete degradation in gastrointestinal tract of mice, and passing through non-degraded particles may negatively affect intestinal system.

Identification of Mouse Cytomegalovirus Resistance Loci by ENU Mutagenesis

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Philippe Georgel

2009-10-01

Full Text Available Host resistance to infection depends on the efficiency with which innate immune responses keep the infectious agent in check. Innate immunity encompasses components with sensing, signaling and effector properties. These elements with nonredundant functions are encoded by a set of host genes, the resistome. Here, we review our findings concerning the resistome. We have screened randomly mutagenized mice for susceptibility to a natural opportunistic pathogen, the mouse cytomegalovirus. We found that some genes with initially no obvious functions in innate immunity may be critical for host survival to infections, falling into a newly defined category of genes of the resistome.

Real-Time PCR of cytomegalovirus and Epstein-Barr virus in adult Egyptian patients with systemic lupus erythematosus.

Science.gov (United States)

Mohamed, Aly E; Hasen, Amany M; Mohammed, Ghada F A; Elmaraghy, Nermin N

2015-05-01

Infections may act as environmental triggers for induction of systemic lupus erythematosus (SLE). We sought to explore the relative frequencies of Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) in adult Egyptian patients with SLE and their correlation with disease activity and damage. Thirty-three consecutive adult patients satisfying the 1997 American College of Rheumatology (ACR) Classification Criteria for SLE and 30 healthy controls were included in this case-control study. All patients were subjected to complete clinical and laboratory evaluation to determine the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR). Sera from both groups were analyzed for immunoglobulin M (IgM) and IgG antibodies against CMV and EBV. Qualitative real time polymerase chain reaction (PCR) for both viruses was performed for all SLE patients. Almost all SLE patients 32/33 (96.9%) were positive for IgG anti-CMV antibodies versus 20/30 in the control group (66.6%) (P = 0.002). All SLE patients were positive for IgG anti-EBV antibodies compared to 25 in the control group (100% vs. 83.3%, P = 0.02). CMV and EBV DNA were detected by PCR in 30.3% and 51.5% of SLE patients, respectively. A statistically significant lower SLEDAI was found in PCR positive patients for EBV compared to negative patients (9.6 ± 5.2 vs. 13.1 ± 3.1, respectively P = 0.041). Adult Egyptian patients with SLE had higher frequencies of anti-CMV and EBV IgG compared to healthy controls. Furthermore, our single point assessment of SLEDAI suggested that exposure to EBV infection might be associated with a lower disease activity. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Congenital Cytomegalovirus Infection in Children with Autism Spectrum Disorder: Systematic Review and Meta-Analysis

Science.gov (United States)

Maeyama, Kaori; Tomioka, Kazumi; Nagase, Hiroaki; Yoshioka, Mieko; Takagi, Yasuko; Kato, Takeshi; Mizobuchi, Masami; Kitayama, Shinji; Takada, Satoshi; Nagai, Masashi; Sakakibara, Nana; Nishiyama, Masahiro; Taniguchi-Ikeda, Mariko; Morioka, Ichiro; Iijima, Kazumoto; Nishimura, Noriyuki

2018-01-01

Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using…

Cytomegalovirus Infections among African-Americans

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Best Al M

2008-08-01

Full Text Available Abstract Background Since African-Americans have twice the prevalence of cytomegalovirus (CMV infections as age-matched Caucasians we sought to determine the ages and possible sources of infection of African-American children. Methods Subjects were 157 African-American healthy children and adolescents and their 113 household adults in Richmond VA. Families completed a questionnaire, provided saliva for antibody testing, and adolescents were interviewed regarding sexual activity. Results Regardless of age CMV seropositivity was not associated with gender, breast feeding, health insurance, sexual activity, or household income, education, or size. In the final regression model, prior CMV infection in adults was over two-fold higher than in children (chi-square = 18.8, p Conclusion We observed that African-American children had CMV seroprevalence rates by age 20 years at less than one-half of that of their adult mothers and caregivers. Sibling-to-sibling transmission was a likely source of CMV infections for the children. The next generation of African-American women may be highly susceptible to a primary CMV infection during pregnancy and may benefit from a CMV vaccine.

Investigation of the Role of the Cytomegalovirus as a Respiratory Pathogen in HIV-Infected Patients

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Rafael E de la Hoz

1996-01-01

Full Text Available OBJECTIVE: To investigate the occurrence of cytomegalovirus (CMV pneumonitis in the setting of human immunodeficiency virus (HIV infection and whether the presence of CMV as copathogen is associated with increased clinical severity or short term mortality in patients with Pneumocystis carinii pneumonia.

Observational study to assess pregnant women’s knowledge and behaviour to prevent toxoplasmosis, listeriosis and cytomegalovirus.

NARCIS (Netherlands)

Pereboom, M.T.R.; Manniën, J.; Spelten, E.R.; Schellevis, F.G.; Hutton, E.K.

2013-01-01

Background: Toxoplasmosis, listeriosis and cytomegalovirus (CMV) can negatively affect pregnancy outcomes, but can be prevented by simple precautions of pregnant women. Literature suggests that pregnant women are not always adequately informed by their care provider about preventable infectious

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study

OpenAIRE

Yamaguchi, Akira; Oh-ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nodoka; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, Tadashi; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

2017-01-01

Objective Approximately 8?10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. Study design The study included 23?368 newborns from two maternity hospitals in Saitama Prefecture, Ja...

Cytomegalovirus: a review of pathogenesis, epidemiology and diagnosis of infection

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Sócrates Bezerra de Matos

2011-01-01

Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as trans placental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

CYTOMEGALOVIRUS: A REVIEW OF PATHOGENESIS, EPIDEMIOLOGY AND DIAGNOSIS OF INFECTION

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Sócrates Bezerra de Matos

2011-05-01

Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as transplacental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

International Nuclear Information System (INIS)

Chattopadhyay, Kausik; Ramagopal, Udupi A.; Nathenson, Stanley G.; Almo, Steven C.

2009-01-01

1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL

1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

Energy Technology Data Exchange (ETDEWEB)

Chattopadhyay, Kausik [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Ramagopal, Udupi A. [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Nathenson, Stanley G., E-mail: nathenso@aecom.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Almo, Steven C., E-mail: nathenso@aecom.yu.edu [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

2009-05-01

1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL.

Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.

Science.gov (United States)

Wagner, Willi; Bennett, Robert D; Ackermann, Maximilian; Ysasi, Alexandra B; Belle, Janeil; Valenzuela, Cristian D; Pabst, Andreas; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

2015-11-01

The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels. © 2015 Wiley Periodicals, Inc.

Primary cytomegalovirus infection in pregnant Egyptian women confirmed by cytomegalovirus IgG avidity testing.

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Kamel, N; Metwally, L; Gomaa, N; Sayed Ahmed, W A; Lotfi, M; Younis, S

2014-01-01

To determine the frequency of primary cytomegalovirus (CMV) infection in pregnant Egyptian women using CMV IgG avidity testing. A cross-sectional study was conducted at Suez Canal University Hospital, Ismailia, Egypt. A total of 546 pregnant women, presenting for routine antenatal screening, were tested for CMV IgG and IgM using a commercially available enzyme-linked immunosorbent assay (ELISA). Sera from CMV IgM-positive women were tested by CMV IgG avidity assay. All the 546 pregnant women were seropositive for anti-CMV IgG. Of the 546 women, 40 (7.3%) were positive or equivocal for IgM antibodies. All sera from the 40 women (IgG+/IgM+) showed a high or intermediate CMV IgG avidity index. Of the 40 women, 23 (57.5%) were in the second or third trimesters of pregnancy and had their first-trimester blood retrieved, and the tested CMV IgG avidity assay showed a high avidity index. Women who were IgM positive had no primary CMV infection in the index pregnancy as evidenced by the high CMV IgG avidity testing. © 2013 S. Karger AG, Basel.

Molecular and Biological Characterization of a New Isolate of Guinea Pig Cytomegalovirus

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Mark R. Schleiss

2014-01-01

Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus is complicated by the issue of re-infection, with subsequent vertical transmission, in women with pre-conception immunity to the virus. The study of experimental therapeutic prevention of re-infection would ideally be undertaken in a small animal model, such as the guinea pig cytomegalovirus (GPCMV model, prior to human clinical trials. However, the ability to model re-infection in the GPCMV model has been limited by availability of only one strain of virus, the 22122 strain, isolated in 1957. In this report, we describe the isolation of a new GPCMV strain, the CIDMTR strain. This strain demonstrated morphological characteristics of a typical Herpesvirinae by electron microscopy. Illumina and PacBio sequencing demonstrated a genome of 232,778 nt. Novel open reading frames ORFs not found in reference strain 22122 included an additional MHC Class I homolog near the right genome terminus. The CIDMTR strain was capable of dissemination in immune compromised guinea pigs, and was found to be capable of congenital transmission in GPCMV-immune dams previously infected with salivary gland‑adapted strain 22122 virus. The availability of a new GPCMV strain should facilitate study of re-infection in this small animal model.

Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN).

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Sfeir, Maroun

2015-08-01

Progressive outer retinal necrosis, also known as PORN, has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with acquired immune deficiency syndrome (AIDS). Although the etiologic organism has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an etiologic agent. Our case illustrates the occurrence of two opportunistic infections: PORN associated with CMV and Mycobacterium avium intracellulare duodenitis in a patient with uncontrolled HIV infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation

NARCIS (Netherlands)

de Rooij, Bert-Jan F.; van der Beek, Martha T.; van Hoek, Bart; Vossen, Ann C. T. M.; ten Hove, W. Rogier; Roos, Anja; Schaapherder, Alexander F.; Porte, Robert J.; van der Reijden, Johan J.; Coenraad, Minneke J.; Hommes, Daniel W.; Verspaget, Hein W.

2011-01-01

Background & Aims: The lectin pathway of complement activation is a crucial effector cascade of the innate immune response to pathogens. Cytomegalovirus (CMV) infection occurs frequently in immunocompromised patients after orthotopic liver transplantation (OLT). Single-nucleotide polymorphisms

Immune Reconstitution Inflammatory Syndrome and Cytomegalovirus Pneumonia Case Report: Highlights and Missing Links in Classification Criteria and Standardized Treatment

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Stefania Petarra-Del Río

2017-01-01

Full Text Available Background. Cytomegalovirus (CMV pulmonary involvement is rarely associated with IRIS; therefore, limited information is available. Case Presentation. Here, we describe the case of a 43-year-old HIV-infected male who developed an unusual case of IRIS after cytomegalovirus (CMV pneumonia. Clinically there was a progressive and paradoxical worsening of respiratory distress, despite being treated for CMV after initiation with antiretroviral therapy. Chest X-ray revealed disseminated infiltrates in both lungs; chest CT-scan showed generalized lung involvement and mediastinal adenopathy. Pulmonary biopsy confirmed CMV pneumonia with the observation of typical viral inclusions on pneumocytes. Conclusions. CMV pneumonia can be associated with the development of IRIS requiring treatment with immunosuppressant’s and immunomodulatory drugs.

DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands

NARCIS (Netherlands)

Korver, A. M. H.; de Vries, J. J. C.; Konings, S.; de Jong, J. W.; Dekker, F. W.; Vossen, A. C. T. M.; Frijns, J. H. M.; Oudesluys-Murphy, A. M.; Wever, C. C.; Beers, M.; Soede, W.; Kant, S. G.; van den Akker-van Marle, M. E.; Rieffe, C.; Ens-Dokkum, M. H.; van Straaten, H. L. M.; Meuwese-Jongejeugd, J.; Elvers, B.; Loeber, G.; Maré, M. J.; Van Zanten, G. A.; Goedegebure, A.; Coster, F.; de Leeuw, M.; Dijkhuizen, J.; Scharloo, M.; Hoeben, D.; Rijpma, G.; Graef, W.; Linschoten, D.; Kuijper, J.; Hof, N. J.; Pans, D.; Jorritsma, F.; van Beurden, M.; ter Huurne, C. T.; Brienesse, P.; Koldewijn, G. J.; Letourneur, K. G.; Seekles, L.; Thijssen, A.; Lievense, A.; van Egdom-van der Wind, M.; Theunissen, S. C. P. M.; Mooij, S.

2009-01-01

A significant number of asymptomatic newborns infected with congenital cytomegalovirus (CMV) will present with permanent childhood hearing impairment (PCHI) during early childhood. To investigate the role of congenital CMV infection in causing PCHI in the Netherlands, and assess the efficacy of two

Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

LENUS (Irish Health Repository)

Monk, Ian R

2010-12-13

Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

Directory of Open Access Journals (Sweden)

Hill Colin

2010-12-01

Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

A Noninvasive In Vitro Monitoring System Reporting Skeletal Muscle Differentiation.

Science.gov (United States)

Öztürk-Kaloglu, Deniz; Hercher, David; Heher, Philipp; Posa-Markaryan, Katja; Sperger, Simon; Zimmermann, Alice; Wolbank, Susanne; Redl, Heinz; Hacobian, Ara

2017-01-01

Monitoring of cell differentiation is a crucial aspect of cell-based therapeutic strategies depending on tissue maturation. In this study, we have developed a noninvasive reporter system to trace murine skeletal muscle differentiation. Either a secreted bioluminescent reporter (Metridia luciferase) or a fluorescent reporter (green fluorescent protein [GFP]) was placed under the control of the truncated muscle creatine kinase (MCK) basal promoter enhanced by variable numbers of upstream MCK E-boxes. The engineered pE3MCK vector, coding a triple tandem of E-Boxes and the truncated MCK promoter, showed twentyfold higher levels of luciferase activation compared with a Cytomegalovirus (CMV) promoter. This newly developed reporter system allowed noninvasive monitoring of myogenic differentiation in a straining bioreactor. Additionally, binding sequences of endogenous microRNAs (miRNAs; seed sequences) that are known to be downregulated in myogenesis were ligated as complementary seed sequences into the reporter vector to reduce nonspecific signal background. The insertion of seed sequences improved the signal-to-noise ratio up to 25% compared with pE3MCK. Due to the highly specific, fast, and convenient expression analysis for cells undergoing myogenic differentiation, this reporter system provides a powerful tool for application in skeletal muscle tissue engineering.

Cytomegalovirus-targeted immunotherapy and glioblastoma: hype or hope?

Science.gov (United States)

Ferguson, Sherise D; Srinivasan, Visish M; Ghali, Michael Gz; Heimberger, Amy B

2016-01-01

Malignant gliomas, including glioblastoma (GBM), are the most common primary brain tumors. Despite extensive research only modest gains have been made in long-term survival. Standard of care involves maximizing safe surgical resection followed by concurrent chemoradiation with temozolomide. Immunotherapy for GBM is an area of intense research in recent years. New immunotherapies, although promising, have not been integrated into standard practice. Human cytomegalovirus (HCMV) is a DNA virus of the family Herpesviridae. Human seroprevalence is approximately 80%, and in most cases, is associated with asymptomatic infection. HCMV may be an important agent in the initiation, promotion and/or progression of tumorigenesis. Regardless of a possible etiologic role in GBM, interest has centered on exploiting this association for development of immunomodulatory therapies.

Mutual Interference between Cytomegalovirus and Reconstitution of Protective Immunity after Hematopoietic Cell Transplantation

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Matthias J. Reddehase

2016-08-01

Full Text Available Hematopoietic cell transplantation (HCT is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a ‘window of opportunity’ for latent cytomegalovirus (CMV by releasing it from immune control with the consequence of reactivation of productive viral gene expression and recurrence of infectious virus. A ‘window of opportunity’ for the virus represents a ‘window of risk’ for the patient. In the interim between HCT and reconstitution of antiviral immunity, primarily mediated by CD8+ T cells, initially low amounts of reactivated virus can expand exponentially, disseminate to essentially all organs, and cause multiple organ CMV disease, with interstitial pneumonia (CMV-IP representing the most severe clinical manifestation. Here I will review predictions originally made in the mouse model of experimental HCT and murine CMV infection, some of which have already paved the way to translational preclinical research and promising clinical trials of a pre-emptive cytoimmunotherapy of human CMV disease. Specifically, the mouse model has been pivotal in providing ‘proof of concept’ for preventing CMV disease after HCT by adoptive transfer of preselected, virus epitope-specific effector and memory CD8+ T cells bridging the critical interim. CMV, however, is not a ‘passive antigen’ but is a pathogen that actively interferes with the reconstitution of protective immunity by infecting bone marrow stromal cells that otherwise form niches for hematopoiesis by providing the structural microenvironment and by producing hematopoietically active cytokines, the hemopoietins. Depending on the precise conditions of HCT, reduced homing of transplanted hematopoietic stem- and progenitor cells to infected bone marrow stroma and impaired colony growth and lineage differentiation can lead to ‘graft failure’. In consequence

Congenital Cytomegalovirus Infection After Recurrent Maternal Infection: Report of a Case

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Özgür Olukman

2005-06-01

Full Text Available Cytomegalovirus (CMV is a double- stranded DNA virus in the Herpesvirus family, and it is a common cause of congenital viral infections. Congenital CMV infection is transmitted from the mother with viremia to the fetus via the placenta. Disease may result from a primary or recurrent maternal infection but the former is a common cause of severe disease. The risk for fetal infection is grater in primary maternal infection. We report a newborn infant with symptomatic congenital CMV infection associated with\trecurrent maternal infection.

Cytomegalovirus-associated colitis mimicking necrotizing enterocolitis – A near miss diagnosis of neonatal colonic stricture

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Fanny Yeung

2014-10-01

Full Text Available Although cytomegalovirus (CMV is a common congenital infection in neonates, most patients are asymptomatic. Gastrointestinal manifestation is unusual. In this report, we described a newborn with perinatal CMV infection presented with symptoms mimicking necrotizing enterocolitis. We hope to alert clinicians about this possible diagnosis when managing newborn gastrointestinal diseases.

FINE SPECIFICITY OF CELLULAR IMMUNE-RESPONSES IN HUMANS TO HUMAN CYTOMEGALOVIRUS IMMEDIATE-EARLY 1-PROTEIN

NARCIS (Netherlands)

ALP, NJ; ALLPORT, TD; VANZANTEN, J; RODGERS, B; SISSONS, JGP; BORYSIEWICZ, LK

Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known

Cytomegalovirus disease in renal transplant recipients: a single-center experience.

Science.gov (United States)

Bhadauria, Dharmendra; Sharma, R K; Kaul, A; Prasad, Narayan; Gupta, Amit; Gupta, Anurag; Srivastava, Aneesh

2012-09-01

Cytomegalovirus (CMV) is the most common viral infection following kidney transplant, has been recognized as a major factor for graft loss and increased incidence of acute rejection. Different studies have reported a variable incidence of CMV disease with the use of Mycophenolate mofetil (MMF). We retrospectively analyzed our renal transplant recipients to review the results of CMV disease and to compare CMV disease in patient on Azathioprine and MMF for this purpose we retrospectively reviewed 521 live related kidney transplant recipients at our institute. 74 (14.2 %) live related allograft recipients developed CMV disease after a median interval of 7.18 ± 4.35 months from transplantation. The mean age was 36.15 ± 10.7 years. 63 of the patients were male. Malaise, fever and diarrhea were among most common symptoms. 20 (27.02 %) of the 74 recipients developed transaminitis, 13 (17.2 %) developed CMV gastritis, 5 (9.13 %) recipients developed pneumonia, and 3 (4.05 %) patient developed colitis. 59 (80 %) patients had leucopenia and 41 (56.5 %) developed thrombocytopenia. Mean serum creatinine level was 1.5 ± 0.4 (0.9-2.4) mg/dl before the disease, 1.9 ± 0.6 (1.3-3.6) mg/dl at the time of the diagnosis, and 1.7 ± 0.06 (0.8-4.2) mg/dl at the end of the treatment. CMV disease developed in 9 (36 %) of recipients who received basiliximab as induction therapy and 13 (30.24 %) of recipients who received ATG (p > 0.05). The incidence of CMV disease was similar in cyclosporine based regimen (13.2 %) and Tacrolimus based regimen 27 (16.16 %) (p = 0.137) and was also similar in Azathioprine 41 (9.5 %) and MMF group 33 (14.3 %) (p = 0.163). There was no significant difference in severity of CMV disease in both groups, except a higher incidence of leucopenia in Azathioprine group (86 vs. 74 %, p < 0.05) as compared to MMF group. 51 (68.91 %) patient developed graft dysfunction during CMV disease. In conclusion we report a low incidence

[Universal cytomegalovirus infection screening in premature newborns less than 1500 g].

Science.gov (United States)

Botet, F; Figueras Aloy, J; Álvarez, E; de Alba, C; Dorronsolo, I; Echaniz Urcelay, I; Rite, S; Moreno, J; Fernández Lorenzo, J R; Herranz Carrillo, G; Salguero, E; Sánchez Luna, M

2014-10-01

Cytomegalovirus (CMV) infection is endemic, and children who attend day care are the most important source of infection. To establish recommendations based on the medical evidence on the vertical transmission of cytomegalovirus in preterm infants weighing less than 1500g at birth. Infection in pregnant women may be primary or secondary. Although there is fetal infection, 85% of newborn infants are asymptomatic. Symptoms of infection include low birth weight, hepatosplenomegaly, thrombocytopenia, microcephaly and neurological disorders. The prognosis of symptomatic children is very poor, with high mortality and neurological disorders. The virus can be reactivated during breast feeding, and early infection is possible through breast milk, probably with little impact in term infants, although the long-term neurological outcome worsens in preterm infants. The diagnostic method of choice is the identification of CMV in urine; the determination in the first two weeks of life suggests congenital infection; later it can be acquired at birth or through breast milk or contaminated blood transfusion. Determine viral DNA at 4-6 weeks of life by protease chain reaction. If it is positive, monitoring of samples from the first days of life and breast milk are mandatory. This should allow the newborn to be classified into three states: "Without CMV infection", "Congenital CMV infection", "Acquired CMV infection". Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Comparative evaluation of the QIAsymphony RGQ system with the easyMAG/R-gene combination for the quantitation of cytomegalovirus DNA load in whole blood

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Pillet Sylvie

2012-10-01

Full Text Available Abstract Background The detection of cytomegalovirus (CMV DNA in blood is a key feature of the virological surveillance of immunocompromised patients. Methods The QIAsymphony RGQ system (QIAGEN S.A.S., France combines the extraction/distribution steps on QIAsymphony SP/AS instruments with amplification on a Rotor-Gene Q RT-PCR machine. This system was compared to a strategy combining an extraction step on the NUCLISENS easyMAG platform (bioMérieux with the CMV R-gene kit (Argene on 100 whole blood specimens collected from immunocompromised patients of the University Hospital of Saint-Etienne, France. Results The overall agreement between the two strategies was 86% (kappa coefficient of 0.67; the 14 discrepant results corresponded to low DNA loads. The 62 samples found positive with both tests were correlated (Pearson r coefficient of 0.70, P 10 copies/ml with the easyMAG/Argene strategy (P 10 copies/ml. The inter-run and intra-run variability was consistently lower with the QIAGEN platform. Conclusions These results validate the performance of the QIAsymphony RGQ system for the routine quantitation of CMV DNA. This fully-automated platform reduces the hands-on time and improves standardization, traceability and quality control assessment.

The human cytomegalovirus US28 protein is located in endocytic vesicles and undergoes constitutive endocytosis and recycling

DEFF Research Database (Denmark)

Fraile-Ramos, A; Kledal, T N; Pelchen-Matthews, A

2001-01-01

Genes encoding chemokine receptor-like proteins have been found in herpes and poxviruses and implicated in viral pathogenesis. Here we describe the cellular distribution and trafficking of a human cytomegalovirus (HCMV) chemokine receptor encoded by the US28 gene, after transient and stable...

Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

International Nuclear Information System (INIS)

Isom, H.C.; Mummaw, J.; Kreider, J.W.

1983-01-01

Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells

Detection of Human Cytomegalovirus and Epstein-Barr Virus in Coronary Atherosclerotic Tissue

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Imbronito, Ana Vitória; Marcelino, Silvia Linardi; Grande, Sabrina Rosa; Nunes, Fabio Daumas; Romito, Giuseppe Alexandre

2010-01-01

Previous studies indicated that patients with atherosclerosis are predominantly infected by human cytomegalovirus (HCMV), but rarely infected by type 1 Epstein-Barr virus (EBV-1). In this study, atheromas of 30 patients who underwent aortocoronary bypass surgery with coronary endartherectomy were tested for the presence of these two viruses. HCMV occurred in 93.3% of the samples and EBV-1 was present in 50% of them. Concurrent presence of both pathogens was detected in 43.3% of the samples. PMID:24031529

Neonatal gastrointestinal involvement and congenital cytomegalovirus

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Alessandro Porta

2016-11-01

Full Text Available Cytomegalovirus (CMV is the most common cause of congenital viral infection, affecting 0.2 to 2.3% of all live births in developed countries. Very low birth weight and extremely low birth weight newborns are at higher risk of symptomatic CMV infection, most commonly secondary and acquired through breast milk. Gastrointestinal involvement is rare in acquired CMV infections, but it could be an important manifestation of postnatal infection in preterm infants admitted to neonatal intensive care units. Early onset of CMV gastrointestinal signs/symptoms is very rare. In a review of the literature it is described in 5 newborns in the first 24 hours of life, and 6 considering the onset in the first week of life. This review describes also a case report of congenital CMV in an immunocompetent newborn with onset of gastrointestinal signs immediately after birth: a possible association between viral infection and enteric manifestations was considered in the differential diagnosis. A review of the literature of the different case reports found has done, with description and comparison of the different patients and clinical presentations.

A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men.

Science.gov (United States)

Adler, Stuart P; Manganello, Anne-Marie; Lee, Ronzo; McVoy, Michael A; Nixon, Daniel E; Plotkin, Stanley; Mocarski, Edward; Cox, Josephine H; Fast, Patricia E; Nesterenko, Pavlo A; Murray, Susan E; Hill, Ann B; Kemble, George

2016-11-01

 Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.  The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted.  There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4 + T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8 + T-cell responses to IE1; 3 responded to 1-2 additional antigens.  The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate.  NCT01195571. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Cytomegalovirus-enhanced development of transplant arteriosclerosis in the rat; effect of timing of infection and recipient responsiveness

NARCIS (Netherlands)

Hillebrands, JL; van Dam, JG; Onuta, G; Klatter, FA; Grauls, G; Bruggeman, CA; Rozing, J

Cytomegalovirus (CMV) is put forward as a risk factor for transplant arteriosclerosis (TA). In this article, we studied CMV-enhanced development of TA in rats in different donor/recipient combinations in relation to the timing of infection. Recipient rats transplanted with an aortic allograft (BN to

Human cytomegalovirus replicates in gamma-irradiated fibroblasts

International Nuclear Information System (INIS)

Shanley, J.D.

1986-01-01

Because of the unique interdependence of human cytomegalovirus (HCMV) and the physiological state of the host cell, we evaluated the ability of human foreskin fibroblasts (HFF), exposed to gamma radiation, to support HCMV growth. Irradiation of HFF with 2,500 rADS prevented cellular proliferation and suppressed cellular DNA, but not RNA or protein synthesis. Treatment of HFF cells with 2,500 rADS 6 or 48 hours prior to infection did not alter the time course or virus yield during HCMV replication. Virus plaquing efficiency in irradiated cells was comparable to that of nonirradiated cells. As judged by thymidine incorporation and BUdR inhibition of virus replication, HCMV infection induced both thymidine kinase activity and host cell DNA synthesis in irradiated cells. In addition, virus could be recovered from HFF exposed to radiation 0-2 days after infection with HCMV. These studies indicate that the damage to cells by gamma irradiation does not alter the capacity of host cells to support HCMV replication

Gastric cancer associated with refractory cytomegalovirus gastritis.

Science.gov (United States)

Ueno, Masayuki; Shimodate, Yuichi; Yamamoto, Shumpei; Yamamoto, Hiroshi; Mizuno, Motowo

2017-12-01

Cytomegalovirus (CMV) sometimes causes gastritis, especially in immunocompromised patients, but whether CMV gastritis promotes the development of gastric cancer is unknown. Here, we report a case of gastric cancer that developed in the presence of CMV gastritis, which had been present for at least 4 years and was refractory to treatment. An 80-year-old woman had noted epigastric discomfort and appetite loss. Esophagogastroduodenoscopy revealed a shallow geographical ulcer extending from the upper body to the pylorus. Histological findings of the biopsy and serology were suggestive of CMV gastritis. Serum anti-Helicobacter pylori antibody test was positive, suggesting co-infection with CMV and H. pylori. Her gastritis was unimproved with repeated antiviral therapy and eradication of H. pylori. Thirty months later, wide-spread gastric cancer had developed. We suggest the possibility that the addition of chronic inflammation of CMV infection to H. pylori-induced gastritis facilitated the development of gastric cancer.

Human Cytomegalovirus: Coordinating Cellular Stress, Signaling, and Metabolic Pathways.

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Shenk, Thomas; Alwine, James C

2014-11-01

Viruses face a multitude of challenges when they infect a host cell. Cells have evolved innate defenses to protect against pathogens, and an infecting virus may induce a stress response that antagonizes viral replication. Further, the metabolic, oxidative, and cell cycle state may not be conducive to the viral infection. But viruses are fabulous manipulators, inducing host cells to use their own characteristic mechanisms and pathways to provide what the virus needs. This article centers on the manipulation of host cell metabolism by human cytomegalovirus (HCMV). We review the features of the metabolic program instituted by the virus, discuss the mechanisms underlying these dramatic metabolic changes, and consider how the altered program creates a synthetic milieu that favors efficient HCMV replication and spread.

The antiviral protein human lactoferrin is distributed in the body to cytomegalovirus (CMV) infection-prone cells and tissues

NARCIS (Netherlands)

Beljaars, Leonie; Bakker, Hester I; van der Strate, Barry W A; Smit, Catharina; Duijvestijn, Adrian M; Meijer, Dirk K F; Molema, Grietje

Purpose. Lactoferrin has anti-Cytomegalovirus (CMV) and -HIV properties in vitro. However, the pharmacokinetic behavior of the 80-kD protein has not been well defined. We, therefore, assessed the plasma decay and body distribution of lactoferrin after intravenous administration to freely moving

Immunobiology of herpes simplex virus and cytomegalovirus infections of the fetus and newborn

OpenAIRE

Muller, William J.; Jones, Cheryl A.; Koelle, David M.

2010-01-01

Immunologic “immaturity” is often blamed for the increased susceptibility of newborn humans to infection, but the precise mechanisms and details of immunologic development remain somewhat obscure. Herpes simplex virus (HSV) and cytomegalovirus (CMV) are two of the more common severe infectious agents of the fetal and newborn periods. HSV infection in the newborn most commonly occurs after exposure to the virus during delivery, and can lead to a spectrum of clinical disease ranging from isolat...

Transient Antiphospholipid Syndrome Associated with Primary Cytomegalovirus Infection: A Case Report and Literature Review

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Tsuyoshi Nakayama

2014-01-01

Full Text Available Viral infection is known to induce transient autoimmunity in humans. Acute cytomegalovirus (CMV infection is implicated in occasional thrombosis formation. We here, for the first time, report a 19-year-old female who had an acute CMV infection, leading to a deep venous thrombosis and a pulmonary embolism along with transient appearance of lupus anticoagulant. The pathological role of antiphospholipid antibodies in CMV-mediated thrombosis is discussed.

Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines

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Shahrzad Fallah

Full Text Available Cytomegalovirus (CMV infection is a common opportunistic systemic infection in immunocompromised patients, but skin involvement is rare. Herein, we report a 10 year-old girl from consanguineous parents who was referred to our center because of disseminated maculopapular rash. She had history of upper and lower respiratory tract infections. In immunological studies, increased serum IgE level and decreased responses to tetanus and diphtheria were detected. Polymerase chain reaction (PCR examination of bronchoalveolar lavage and serum sample revealed the presence of CMV. Early diagnosis of cutaneous CMV and appropriate treatment are the key actions in management of patients with underlying immunodeficiencies to avoid further complications.

Anatomy and Histology of the Human and Murine Prostate.

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Ittmann, Michael

2018-05-01

The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

MHC class I Dk locus and Ly49G2+ NK cells confer H-2k resistance to murine cytomegalovirus.

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Xie, Xuefang; Stadnisky, Michael D; Brown, Michael G

2009-06-01

Essential NK cell-mediated murine CMV (MCMV) resistance is under histocompatibility-2(k) (H-2(k)) control in MA/My mice. We generated a panel of intra-H2(k) recombinant strains from congenic C57L.M-H2(k/b) (MCMV resistant) mice for precise genetic mapping of the critical interval. Recombination breakpoint sites were precisely mapped and MCMV resistance/susceptibility traits were determined for each of the new lines to identify the MHC locus. Strains C57L.M-H2(k)(R7) (MCMV resistant) and C57L.M-H2(k)(R2) (MCMV susceptible) are especially informative; we found that allelic variation in a 0.3-megabase interval in the class I D locus confers substantial difference in MCMV control phenotypes. When NK cell subsets responding to MCMV were examined, we found that Ly49G2(+) NK cells rapidly expand and selectively acquire an enhanced capacity for cytolytic functions only in C57L.M-H2(k)(R7). We further show that depletion of Ly49G2(+) NK cells before infection abrogated MCMV resistance in C57L.M-H2(k)(R7). We conclude that the MHC class I D locus prompts expansion and activation of Ly49G2(+) NK cells that are needed in H-2(k) MCMV resistance.

Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication.

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Nicolas Caffarelli

Full Text Available Cyclin A is critical for cellular DNA synthesis and S phase progression of the cell cycle. Human cytomegalovirus (HCMV can reduce cyclin A levels and block cellular DNA synthesis, and cyclin A overexpression can repress HCMV replication. This interaction has only been previously observed in HCMV as murine CMV does not downregulate cyclin A, and the responsible viral factor has not been identified. We previously reported that the HCMV protein pUL21a disrupted the anaphase-promoting complex (APC, but a point mutant abrogating this activity did not phenocopy a UL21a-deficient virus, suggesting that pUL21a has an additional function. Here we identified a conserved arginine-x-leucine (RxL cyclin-binding domain within pUL21a, which allowed pUL21a to interact with cyclin A and target it for proteasome degradation. Homologous pUL21a proteins from both chimpanzee and rhesus CMVs also contained the RxL domain and similarly degraded cyclin A, indicating that this function is conserved in primate CMVs. The RxL point mutation disabled the virus' ability to block cellular DNA synthesis and resulted in a growth defect similar to pUL21a-deficient virus. Importantly, knockdown of cyclin A rescued growth of UL21a-deficient virus. Together, these data show that during evolution, the pUL21a family proteins of primate CMVs have acquired a cyclin-binding domain that targets cyclin A for degradation, thus neutralizing its restriction on virus replication. Finally, the combined proteasome-dependent degradation of pUL21a and its cellular targets suggests that pUL21a may act as a novel suicide protein, targeting its protein cargos for destruction.

Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the human cytomegalovirus UL127 and major immediate-early genes

International Nuclear Information System (INIS)

Lee Jialing; Klase, Zachary; Gao Xiaoqi; Caldwell, Jeremy S.; Stinski, Mark F.; Kashanchi, Fatah; Chao, S.-H.

2007-01-01

An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal, P., 2000. Identification of a boundary domain adjacent to the potent human cytomegalovirus enhancer that represses transcription of the divergent UL127 promoter. J. Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski, M.F., 1999. A strong negative transcriptional regulatory region between the human cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73 (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was identified in the UR and found to play a key role in repression of the UL127 promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A., Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113-5123]. However, the cellular factors which associate with the UR and FOX-like region remain to be determined. We reported previously that pancreatic-duodenal homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao, S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell, J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111-16120]. Here we demonstrate that two additional cellular homeoproteins, special AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP), bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as a FOX-like binding protein

Antibodies to early EBV, CMV, and HHV6 antigens in systemic lupus erythematosus patients

DEFF Research Database (Denmark)

Rasmussen, N S; Draborg, A H; Nielsen, C T

2015-01-01

OBJECTIVES: We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology/biochemistry, serol......OBJECTIVES: We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology...

Performance Evaluation of the Real-Q Cytomegalovirus (CMV) Quantification Kit Using Two Real-Time PCR Systems for Quantifying CMV DNA in Whole Blood.

Science.gov (United States)

Park, Jong Eun; Kim, Ji Youn; Yun, Sun Ae; Lee, Myoung Keun; Huh, Hee Jae; Kim, Jong Won; Ki, Chang Seok

2016-11-01

Standardized cytomegalovirus (CMV) DNA quantification is important for managing CMV disease. We evaluated the performance of the Real-Q CMV Quantification Kit (Real-Q assay; BioSewoom, Korea) using whole blood (WB), with nucleic acid extraction using MagNA Pure 96 (Roche Diagnostics, Germany). Real-time PCR was performed on two platforms: the 7500 Fast real-time PCR (7500 Fast; Applied Biosystems, USA) and CFX96 real-time PCR detection (CFX96; Bio-Rad, USA) systems. The WHO international standard, diluted with CMV-negative WB, was used to validate the analytical performance. We used 90 WB clinical samples for comparison with the artus CMV RG PCR kit (artus assay; Qiagen, Germany). Limits of detections (LODs) in 7500 Fast and CFX96 were 367 and 479 IU/mL, respectively. The assay was linear from the LOD to 10⁶ IU/mL (R² ≥0.9886). The conversion factors from copies to IU in 7500 Fast and CFX96 were 0.95 and 1.06, respectively. Compared with the artus assay, for values 1,000 copies/mL, 73.3% and 80.6% of samples in 7500 Fast and CFX96, respectively, had real-time PCR platforms.

Real-time PCR versus viral culture on urine as a gold standard in the diagnosis of congenital cytomegalovirus infection

NARCIS (Netherlands)

de Vries, Jutte J. C.; van der Eijk, Annemiek A.; Wolthers, Katja C.; Rusman, Lisette G.; Pas, Suzan D.; Molenkamp, Richard; Claas, Eric C.; Kroes, Aloys C. M.; Vossen, Ann C. T. M.

2012-01-01

Background: Cytomegalovirus (CMV) infection is the most common cause of congenital infection. Whereas CMV PCR has replaced viral culture and antigen detection in immunocompromised patients because of higher sensitivity, viral culture of neonatal urine is still referred to as the gold standard in the

Initial cytomegalovirus prophylaxis with ganciclovir : no guarantee for prevention of late serious manifestations of CMV after solid organ transplantation

NARCIS (Netherlands)

Zandberg, M; de Maar, EF; Hofker, HS; van der Heide, JJH; Rosati, S; van Son, WJ

2005-01-01

A 37-year-old woman presented with malaise, upper abdominal pain and fever seven months after renal transplantation. She was seronegative for cytomegalovirus (CMV) and had received a kidney from a seropositive donor. She had received CMV prophylaxis (oral ganciclovir) for three months after

Functional analysis of the human cytomegalovirus immune evasion protein, pUS322kDa

International Nuclear Information System (INIS)

Zhao Yiqiang; Biegalke, Bonita J.

2003-01-01

Human cytomegalovirus (HCMV) is an important opportunistic pathogen that infrequently causes disease in individuals with mature immune systems. The HCMV US3 gene encodes a 22-kDa protein that interferes with immune recognition of virally infected cells. The 22-kDa US3 protein binds to major histocompatibility complex (MHC) class I complexes, retaining them in the endoplasmic reticulum (ER), thereby decreasing the presentation of viral antigen to cytotoxic T cells. Our studies demonstrate that correct folding of the ER lumenal domain of the US3 protein is essential, but insufficient for interactions with MHC class I complexes. We demonstrate a requirement for the transmembrane domain of the 22-kDa US3 protein, confirming the results of others, and also show that the cytosolic carboxyl-terminal tail influences the function of the protein. Anchoring of the ER-lumenal immunoglobulin-like fold of the US3 protein to the membrane of the endoplasmic reticulum is critical for the binding and retention of MHC class I complexes

Septic Shock due to Cytomegalovirus Infection in Acute Respiratory Distress Syndrome after Falciparum Malaria.

Science.gov (United States)

Harbarth; Meyer; Grau; Loutan; Ricou

1997-09-01

Incidence of falciparum malaria in developed countries has increased in recent years due to tourism to tropical countries and immigration from Asia and Africa. In Switzerland, about 250 cases of malaria were reported in 1994 to the Federal Office of Health, including three cases with fatal outcome.1 The most commonly described complications of plasmodia infection are cerebral malaria, acute renal failure, and severe anemia with disseminated intravascular coagulation. However, pulmonary involvement occurs in 3 to 10% of cases and represents the most serious complication of this infection, with a lethality of 70%.2,3 Furthermore, a pronounced general immunosuppression has been reported in malaria patients, which may predispose them to opportunistic infections.4 We report a case of Plasmodium falciparum infection complicated by severe acute respiratory distress syndrome (ARDS) with development of systemic cytomegalovirus (CMV) infection leading to death. This evolution implies a severe immune deficiency associated with malaria, as previously suggested in the literature.

Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan.

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Ghulam Mujtaba

Full Text Available Congenital cytomegalovirus (cCMV infection contributes to considerable long-term sequelae in neonates and children all over the world. The association between viral genotypes and severity of clinical cytomegalovirus (CMV infection is yet to be defined. The objective of this study was to find the impact of active CMV infection during pregnancy and the clinical significance of genotypes in neonates with congenital cytomegalovirus infections in Pakistan.A total of 409 blood samples from pregnant women seeking health care services at the two antenatal hospitals of Islamabad during January to December 2012 were tested by ELISA and nested-PCR. Pregnant women with active infection (detected as IgM positive, PCR positive or positive on both assays were followed until delivery, to detect the outcome of overt cCMV infection in neonates. Genetic characterization of CMV strains was performed by sequence analysis of envelope glycoproteins: gB, gN and gH to detect the contributing CMV genotypes.The seroprevalence of anti-CMV IgG and IgM was 97.5% (399 out of 409 and 12.7% (52 out of 409, respectively, while 20% (82/409 pregnant women were found positive for CMV DNA by PCR. Logistic regression analysis showed a significant association of active infection with parity [OR = 2.56, 95% CI = 1.82-2.62, p = 0.04], febrile illness [OR = 1.84, 95% CI = 1.76-3.65, p = 0.01] and jaundice [OR = 22.5, 95% CI = 4.53-85.02, p = 0.002]. We were able to isolate virus in 41 out of 70 neonates; 36.6% (15 out of 41 of them were symptomatic at birth while 63.4% (26 out of 41 were asymptomatic. The most prominent clinical feature observed in symptomatic neonates was hepatosplenomegaly (26.6%; 4 out of 15. All three genotypes gB, gN and gH were found with the highest frequency of gB1 genotype, found in 75% infants with hepatic damage. Phylogenetic analysis of Pakistani strains showed 96%-100% homology to their prototype strains.Active CMV infection during pregnancy is a major cause

Splenic Infarct and Pulmonary Embolism as a Rare Manifestation of Cytomegalovirus Infection

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Prashanth Rawla

2017-01-01

Full Text Available Cytomegalovirus (CMV is a type of herpes infection that has a characteristic feature of maintaining lifelong latency within the host cell. CMV manifestations can cover a broad spectrum from fever to as severe as pancytopenia, hepatitis, retinitis, meningoencephalitis, Guillain-Barre syndrome, pneumonia, and thrombosis. Multiple case reports of thrombosis associated with CMV have been reported. Deep vein thrombosis or pulmonary embolism is more common in immunocompetent patients while splenic infarct is more common in immunocompromised patients. However, here we report a female patient on low-dose methotrexate for rheumatoid arthritis who presented with both pulmonary embolism and splenic infarct.

[Primary infection with cytomegalovirus: An infectious cause of splenic infarction].

Science.gov (United States)

Kassem, H; Khamadi, K; Farrugia, C; Ho Hio Hen, N; El Gharbi, T; Turner, L

2017-08-01

Cytomegalovirus-associated thrombosis has been extensively reported in the medical literature, mainly in immune-compromised patients. However, the association with splenic infarcts has rarely been reported. We report a 32-year-old Caucasian and immunocompetent woman who presented with a splenic infarction during a primary infection with CMV. The differential diagnostic ruled out embolic, hematologic, gastrointestinal and coagulation disorders. The outcome was favorable with symptomatic treatment. A primary infection with CMV must be added to the diagnostic work-up in the presence of a febrile splenic infarction, especially when it is associated with a biological mononucleosis reaction. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Congenital Cytomegalovirus Hepatitis in the XXI Century is not Uncommon!

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N.P. Skorodumova

2014-08-01

Full Text Available The article presents features of early clinical and laboratory diagnosis of congenital cytomegalovirus (CMV hepatitis. The analysis of the causes of late diagnosis of chronic hepatitis is carried out. Some children have repeatedly appealed to the doctor and treated for gastroduodenitis, cholecystitis, biliary dyskinesia, ulcerative colitis. Chart review allowed to assume that the extrahepatic manifestations of chronic hepatitis and liver cirrhosis district pediatricians interpreted as allergy (recurrent urticaria, juvenile rheumatoid arthritis (arthritis, vegetovascular dystonia (ECG changes; endocrine violations (delayed menstruation, striae on the abdominal skin — as the feature of puberty; signs of hypo- or hyperthyroidism — as endemic pathology. A sequence of doctor’s actions in diagnosing congenital CMV infection, mainly affecting the liver, is provided.

Cytomegalovirus-associated Immune Thrombocytopenic Purpura After Liver Transplantation

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Shu-Hao Wei

2007-01-01

Full Text Available Immune thrombocytopenic purpura (ITP is a rare complication after liver transplantation. Infection with cytomegalovirus (CMV is a frequent complication of organ transplantation and may induce autoimmune diseases, such as ITP. We report a case of ITP after primary CMV infection in a 3-year-old boy recipient of living-related orthotopic liver transplantation (OLT. The ITP developed 2 years after OLT in this patient who had received tacrolimus as an immunosuppressive agent, with nadir platelet counts of 5000/mm3 in 2 weeks. The patient was treated with two courses of intravenous gamma globulin (1 g/kg/day for 2 days and subsequent oral prednisolone (1.3 mg/kg/day for 2 weeks. He recovered from thrombocytopenia 4 weeks later. An inadequate immunosuppression, as evident by the low serum tacrolimus level (5.8 ng/mL before the episode of ITP in this patient, may allow the development of ITP after CMV infection. [J Formos Med Assoc 2007;106(4:327-329

Knowledge and Awareness of Congenital Cytomegalovirus Among Women

Science.gov (United States)

Jeon, Jiyeon; Victor, Marcia; Adler, Stuart P.; Arwady, Abigail; Demmler, Gail; Fowler, Karen; Goldfarb, Johanna; Keyserling, Harry; Massoudi, Mehran; Richards, Kristin; Staras, Stephanie A. S.; Cannon, Michael J.

2006-01-01

Background. Congenital cytomegalovirus (CMV) infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. Methods. Women were surveyed about newborn infections at 7 different geographic locations. Results. Of the 643 women surveyed, 142 (22%) had heard of congenital CMV. Awareness increased with increasing levels of education (P < .0001). Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women (56% versus 16%, P < .0001). Women who were aware of CMV were most likely to have heard about it from a healthcare provider (54%), but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. Conclusion. Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies. PMID:17485810

Knowledge and Awareness of Congenital Cytomegalovirus Among Women

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Jiyeon Jeon

2006-01-01

Full Text Available Background. Congenital cytomegalovirus (CMV infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. Methods. Women were surveyed about newborn infections at 7 different geographic locations. Results. Of the 643 women surveyed, 142 (22% had heard of congenital CMV. Awareness increased with increasing levels of education (P<.0001. Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women (56% versus 16%, P <.0001. Women who were aware of CMV were most likely to have heard about it from a healthcare provider (54%, but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. Conclusion. Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies.

Murine CMV-Induced Hearing Loss Is Associated with Inner Ear Inflammation and Loss of Spiral Ganglia Neurons

OpenAIRE

Bradford, Russell D.; Yoo, Young-Gun; Golemac, Mijo; Pugel, Ester Pernjak; Jonjic, Stipan; Britt, William J.

2015-01-01

Author Summary Congenital infection with human cytomegalovirus (HCMV) is the most common viral infection of the fetus and occurs in 0.5?2.0% of all live births in most regions in the world. Infection of the fetus can result in a spectrum of end-organ disease, including long term damage to the central nervous system (CNS). Although less than 10% of infected infants exhibit clinical evidence of end-organ disease, up to 10% of the total number of infected infants develop hearing loss. Mechanisms...

Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo

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Christoph Hirche

2017-06-01

Full Text Available Quiescent long-term hematopoietic stem cells (LT-HSCs are efficiently activated by type I interferon (IFN-I. However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV and murine cytomegalovirus (MCMV infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute inflammatory stimuli in bone marrow donors can affect the reconstitution potential of bone marrow transplants.

Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo.

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Hirche, Christoph; Frenz, Theresa; Haas, Simon F; Döring, Marius; Borst, Katharina; Tegtmeyer, Pia-K; Brizic, Ilija; Jordan, Stefan; Keyser, Kirsten; Chhatbar, Chintan; Pronk, Eline; Lin, Shuiping; Messerle, Martin; Jonjic, Stipan; Falk, Christine S; Trumpp, Andreas; Essers, Marieke A G; Kalinke, Ulrich

2017-06-13

Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute inflammatory stimuli in bone marrow donors can affect the reconstitution potential of bone marrow transplants. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Magnetic resonance imaging of the brain in congenital rubella virus and cytomegalovirus infections

International Nuclear Information System (INIS)

Sugita, K.; Ando, M.; Makino, M.; Takanashi, J.; Fujimoto, N.; Niimi, H.

1991-01-01

Two children with congenital rubella virus and six with cytomegalovirus (CMV) infections, were examined by magnetic resonance (MR) and CT. Cranial MR imaging (MRI) with T2-weighted spin-echo (SE) and inversion recovery (IR) sequences demonstrated the following: Periventricular hyperintensity (4), subcortical hyperintensity (5), delayed myelination (4), oligo/pachygyria (2), cerebellar hypoplasia (2). This study showed that the more-disabled children had more marked abnormal MRI findings. MRI was more effective in the detection of parenchymal lesion than was CT, although intraventricular calcification was better visualized with CT. (orig.)

Human cytomegalovirus chemokine receptor US28 induces migration of cells on a CX3CL1-presenting surface

DEFF Research Database (Denmark)

Hjortø, Gertrud M; Kiilerich-Pedersen, Katrine; Selmeczi, David

2013-01-01

Human cytomegalovirus (HCMV)-encoded G protein-coupled-receptor US28 is believed to participate in virus dissemination through modulation of cell migration and immune evasion. US28 binds different CC chemokines and the CX3C chemokine CX3CL1. Membrane-anchored CX3CL1 is expressed by immune-activat...

Murine Models of Gastric Corpus PreneoplasiaSummary

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Christine P. Petersen

2017-01-01

Full Text Available Intestinal-type gastric adenocarcinoma evolves in a field of pre-existing metaplasia. Over the past 20 years, a number of murine models have been developed to address aspects of the physiology and pathophysiology of metaplasia induction. Although none of these models has achieved true recapitulation of the induction of adenocarcinoma, they have led to important insights into the factors that influence the induction and progression of metaplasia. Here, we review the pathologic definitions relevant to alterations in gastric corpus lineages and classification of metaplasia by specific lineage markers. In addition, we review present murine models of the induction and progression of spasmolytic polypeptide (TFF2–expressing metaplasia, the predominant metaplastic lineage observed in murine models. These models provide a basis for the development of a broader understanding of the physiological and pathophysiological roles of metaplasia in the stomach. Keywords: SPEM, Intestinal Metaplasia, Gastric Cancer, TFF2, Chief Cell, Hyperplasia

Use of Molecular Assays in Diagnosis and Monitoring of Cytomegalovirus Disease following Renal Transplantation

OpenAIRE

Aitken, Celia; Barrett-Muir, Winsome; Millar, Colin; Templeton, Kate; Thomas, Janice; Sheridan, Fran; Jeffries, Donald; Yaqoob, Magdi; Breuer, Judith

1999-01-01

We compared two commercial molecular assays (the Murex Hybrid Capture CMV DNA assay [HCA], version 2, and the Roche Amplicor plasma PCR assay) with a standard shell vial assay in detecting and predicting cytomegalovirus (CMV) disease in a group of renal transplant patients and assessed the role of viral load measurements (using the HCA) in their management. The sensitivity of the HCA and Amplicor assay in terms of disease detection was 100%, compared to 71% for the shell vial assay. Both the ...

Murine Typhus: An Important Consideration for the Nonspecific Febrile Illness

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Gurjot Basra

2012-01-01

Full Text Available Murine typhus is a widely distributed flea-borne infection caused by Rickettsia typhi. Symptoms of murine typhus are nonspecific and mimic a variety of other infectious diseases. We herein report a case of murine typhus in an area where the broad use of DDT in the mid-20th century has now made it a rare disease. The patient described presented with headache, fever, and a faint macular rash. Initial laboratory studies revealed a slight transaminase elevation. Further questioning revealed exposure to opossums, prompting the consideration of murine typhus as a diagnosis. Although typhus group antibodies were not present during the patient’s acute illness, empiric therapy with doxycycline was initiated, and the patient defervesced. One month after convalescence, the patient returned to clinic with serum that contained typhus group antibodies with an IgG titer of 1 : 1024. Murine typhus is an important consideration during the workup of a patient with a nonspecific febrile illness. Exposure to reservoir hosts and the flea vector place humans at risk for this disease. Clinician recognition of this entity is required for diagnosis and effective therapy.

No. 240-Cytomegalovirus Infection in Pregnancy.

Science.gov (United States)

Yinon, Yoav; Farine, Dan; Yudin, Mark H

2018-02-01

To review the principles of prenatal diagnosis of congenital cytomegalovirus (CMV) infection and to describe the outcomes of the affected pregnancies. Effective management of fetal infection following primary and secondary maternal CMV infection during pregnancy. Neonatal signs include intrauterine growth restriction (IUGR), microcephaly, hepatosplenomegaly, petechiae, jaundice, chorioretinitis, thrombocytopenia and anemia, and long-term sequelae consist of sensorineural hearing loss, mental retardation, delay of psychomotor development, and visual impairment. These guidelines provide a framework for diagnosis and management of suspected CMV infections. Medline was searched for articles published in English from 1966 to 2009, using appropriate controlled vocabulary (congenital CMV infection) and key words (intrauterine growth restriction, microcephaly). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated into the guideline. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Copyright © 2018. Published by Elsevier Inc.

Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28

NARCIS (Netherlands)

Hulshof, Janneke W; Casarosa, Paola; Menge, Wiro M P B; Kuusisto, Leena M S; van der Goot, Henk; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

2005-01-01

US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 [5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile] as the first reported nonpeptidergic inverse agonist for a viral-encoded

Novel Application of Micro-Computerized Tomography for Morphologic Characterization of the Murine Penis.

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O'Neill, Marisol; Huang, Gene O; Lamb, Dolores J

2017-12-01

The murine penis model has enriched our understanding of anomalous penile development. The morphologic characterization of the murine penis using conventional serial sectioning methods is labor intensive and prone to errors. To develop a novel application of micro-computerized tomography (micro-CT) with iodine staining for rapid, non-destructive morphologic study of murine penis structure. Penises were dissected from 10 adult wild-type mice and imaged using micro-CT with iodine staining. Images were acquired at 5-μm spatial resolution on a Bruker SkyScan 1272 micro-CT system. After images were acquired, the specimens were washed of any remaining iodine and embedded in paraffin for conventional histologic examination. Histologic and micro-CT measurements for all specimens were made by 2 independent observers. Measurements of penile structures were made on virtual micro-CT sections and histologic slides. The Lin concordance correlation coefficient demonstrated almost perfect strength of agreement for interobserver variability for histologic section (0.9995, 95% CI = 0.9990-0.9997) and micro-CT section (0.9982, 95% CI = 0.9963-0.9991) measurements. Bland-Altman analysis for agreement between the 2 modalities of measurement demonstrated mean differences of -0.029, 0.022, and -0.068 mm for male urogenital mating protuberance, baculum, and penile glans length, respectively. There did not appear to be a bias for overestimation or underestimation of measured lengths and limits of agreement were narrow. The enhanced ability offered by micro-CT to phenotype the murine penis has the potential to improve translational studies examining the molecular pathways contributing to anomalous penile development. The present study describes the first reported use of micro-CT with iodine staining for imaging the murine penis. Producing repeated histologic sections of identical orientation was limited by inherent imperfections in mounting and tissue sectioning, but this was

Maternal Cytomegalovirus-Specific Immune Responses and Symptomatic Postnatal Cytomegalovirus Transmission in Very Low-Birth-Weight Preterm Infants

Science.gov (United States)

Ehlinger, Elizabeth P.; Webster, Emily M.; Kang, Helen H.; Cangialose, Aislyn; Simmons, Adam C.; Barbas, Kimberly H.; Burchett, Sandra K.; Gregory, Mary L.; Puopolo, Karen P.

2011-01-01

Introduction. Transmission of cytomegalovirus (CMV) via breast milk can lead to severe acute illness in very low-birth-weight (VLBW) preterm infants. Although the majority of CMV-seropositive women shed CMV in milk, symptomatic postnatal infection of VLBW infants occurs infrequently, suggesting that virologic or immunologic factors in milk may be associated with the risk and severity of postnatal CMV infection. Methods. We investigated the magnitude of CMV-specific cellular and humoral immune responses in milk of 30 seropositive mothers of VLWB preterm infants and assessed their relationship to milk CMV load and symptomatic CMV transmission. Results. Milk immunoglobulin G (IgG) avidity was inversely correlated to milk CMV load (r = −0.47; P = .009). However, milk CMV load and CMV-specific cellular and humoral immune responses were similar in mothers of VLBW infants with and those without symptomatic postnatal CMV infection. Conclusions. Similar immunologic parameters in milk of CMV-seropositive mothers of VLBW infants with and without symptomatic postnatal CMV infection indicate that screening milk by these parameters may not predict disease risk. However, the inverse correlation between milk CMV IgG avidity and CMV load may suggest that enhancement of maternal CMV-specific IgG responses could aid in reduction of CMV shedding into breast milk. PMID:21984738

Synchronous cytomegalovirus infection in a newly diagnosed ulcerative colitis patient

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Jin Yu Chieng

2017-12-01

Full Text Available A 61-year-old Punjabi female patient presented with six months history of mild abdominal discomfort with bloody diarrhea. She did not have underlying chronic medical illness; she neither took steroid nor immunosuppressant. She was found anemic, thrombocytosis, and elevated C-reactive protein. Colonoscopy showed moderate left sided colitis, with histopathology evidence of ulcerative colitis (UC with cytomegalovirus (CMV infection. Her serum anti-CMV IgM antibody was detected. She was treated with intravenous ganciclovir, together with 5-ASA and tapering dose of steroid. Anemia was corrected. Subsequent clinic reviews and follow up endoscopies showed dramatically improvement. CMV colitis should be considered for the patients presenting with moderate to severe UC. Early prescription of antiviral would be beneficial in the treatment of flare of UC.

Identification of Persistent RNA-DNA Hybrid Structures within the Origin of Replication of Human Cytomegalovirus

OpenAIRE

Prichard, Mark N.; Jairath, Sanju; Penfold, Mark E. T.; Jeor, Stephen St.; Bohlman, Marlene C.; Pari, Gregory S.

1998-01-01

Human cytomegalovirus (HCMV) lytic-phase DNA replication initiates at the cis-acting origin of replication, oriLyt. oriLyt is a structurally complex region containing repeat elements and transcription factor binding sites. We identified two site-specific alkali-labile regions within oriLyt which flank an alkali-resistant DNA segment. These alkali-sensitive regions were the result of the degradation of two RNA species embedded within oriLyt and covalently linked to viral DNA. The virus-associa...

A Novel Murine Candidiasis Model with Severe Colonization in the Stomach Induced by N-acetylglucosamine-treatment and Its Scoring System Based on Local Characteristic Stomach Symptoms.

Science.gov (United States)

Ishijima, Sanae A; Abe, Shigeru

2015-01-01

We developed a novel murine candidiasis model of the gastrointestinal tract using N-acetylglucosamine ( GlcNAc ) as a tool to aggravate symptoms. Forty-eight hours after intragastrically inoculating Candida albicans cells to immunosuppressed and GlcNAc-treated mice, vigorously accumulating patchy whitish plaques were observed on their inner stomach surface. Candida cells colonizing the plaques consisted of both yeast and mycelia, and were directly stained with Calcofluor White M2R. Aggravation of the candidiasis symptoms was dependent on GlcNAc concentration in drinking water, wherein administration of 50 mM GlcNAc not only severely worsened stomach symptoms, but also significantly increased Candida cell number in the stomach and small intestine. The aggravation effect of GlcNAc was enhanced by addition of sedative chemical chlorpromazine chloride after inoculation. In order to semi-quantitatively assess colonization by Candida in the stomach, we devised a new symptom scoring system that represents the extent of the patchy whitish plaques on the mucosal epithelium of the stomach. Histochemical analysis of Candida-infected tissues revealed not only a large amount of thick Candida mycelia invading mucosal epithelial stomach tissues but also infiltrating inflammatory cells. These results suggest that this murine gastrointestinal candidiasis model could serve as a useful tool for evaluating the protective activity of antifungal agents, probiotics, or functional foods against gastrointestinal candidiasis. Furthermore, from another point of view, this novel murine model could also be used to analyze the pathological mechanisms behind the translocation of C. albicans across intestinal barriers, which results in systemic Candida dissemination and infection.

Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

Energy Technology Data Exchange (ETDEWEB)

Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

1995-06-15

To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

International Nuclear Information System (INIS)

Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won; Park, Choong Ki

1995-01-01

To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly (ρ < 0.01) and azygos engorgement (ρ < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality

Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

Energy Technology Data Exchange (ETDEWEB)

Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

1995-06-15

To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus.

Science.gov (United States)

Abou, Magali; Dällenbach, Patrick

2013-04-19

Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported. A 24-year-old woman presented with pelvic pain, vulvodynia, abnormal vaginal discharge, burning with urination, fatigue, fever, vomiting and diarrhoea. The vulva and cervix were red with vesicular lesions on the cervix. Genital herpes simplex infection (HSV) was suspected and valacyclovir was given orally. However, serial viral cultures performed 7 weeks apart did not isolate HSV as suspected, but CMV was confirmed by immunofluorescence and early antigen research. Blood tests confirmed an acute CMV infection. Typical inclusions were found at histology. Symptoms resolved slowly with persistence of cervical lesions at 7 weeks from diagnosis. The frequency of CMV genital infection is probably underestimated. The infection is not always asymptomatic and might be confused with genital HSV infection. The clinical course is longer.

The Cytomegalovirus UL146 Gene Product vCXCL1 Targets Both CXCR1 and CXCR2 as an Agonist

DEFF Research Database (Denmark)

Luttichau, H.R.

2010-01-01

Large DNA viruses, such as herpesvirus and poxvirus, encode proteins that target and exploit the chemokine system of their host. UL146 and UL147 in the cytomegalovirus (CMV) genome encode the two CXC chemokines vCXCL1 and vCXCL2. In this study, vCXCL1 was probed against a panel of the 18 classified...... human chemokine receptors. In calcium mobilization assays vCXCL1 acted as an agonist on both CXCR1 and CXCR2 but did not activate or block any of the other 16 chemokine receptors. vCXCL1 was characterized and compared with CXCL1/GRO alpha, CXCL2/GRO beta, CXCL3/GRO gamma, CXCL5/ENA-78, CXCL6/GCP2, CXCL7...

Increased Cytomegalovirus Secretion and Risks of Infant Infection by Breastfeeding Duration From Maternal Human Immunodeficiency Virus Positive Compared to Negative Mothers in Sub-Saharan Africa.

Science.gov (United States)

Musonda, Kunda G; Nyonda, Mary; Filteau, Suzanne; Kasonka, Lackson; Monze, Mwaka; Gompels, Ursula A

2016-06-01

Breastfeeding imparts beneficial immune protection and nutrition to infants for healthy growth, but it is also a route for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. In previous studies, we showed that HCMV adversely affects infant development in Africa, particularly with maternal HIV exposure. In this study, we analyzed infants risks for acquisition of HCMV infection from breastfeeding and compared HIV-positive and HIV-negative mothers. Two cohorts were studied in Zambia. (1) Two hundred sixty-one HIV-infected and HIV-uninfected mothers were compared for HCMV deoxyribonucleic acid (DNA) loads and genotypes (glycoprotein gO) in milk from birth to 4 months postpartum. (2) Maternally HIV-exposed and HIV-unexposed infants were compared for HCMV infection risk factors. The second cohort of 460 infants, from a trial of micronutrient-fortified complementary-food to breastfeeding, were studied between 6 and 18 months of age. Human cytomegalovirus seroprevalence was assayed, and logistic regression was used to calculate risk factors for HCMV infection, including maternal HIV exposure and breastfeeding duration. Human cytomegalovirus was detected in breast milk from 3 days to 4 months postpartum, with significantly raised levels in HIV-positive women and independent of genotype. In infants, HCMV antibody seroprevalence was 83% by 18 months age. Longer breastfeeding duration increased infection risk in maternally HIV-unexposed (odds ratio [OR] = 2.69 for 18 months vs 6 months vs never; 95% CI, 3.71-111.70; P breastfeeding, which is common in Africa, increased risk of HCMV infection in infants. Both HIV-positive and HIV-negative women had extended milk HCMV secretion. Women who were HIV-positive secreted higher HCMV levels, and for longer duration, with their children at increased infection risk. Human cytomegalovirus control is required to maintain health benefits of breastfeeding. © The Author 2016. Published by Oxford University Press

Human cytomegalovirus and Epstein-Barr virus type 1 in periodontal abscesses.

Science.gov (United States)

Saygun, I; Yapar, M; Ozdemir, A; Kubar, A; Slots, J

2004-04-01

Recent studies have linked herpesviruses to severe types of periodontal disease, but no information exists on their relationship to periodontal abscesses. The present study determined the presence of human cytomegalovirus (HCMV) and Epstein-Barr virus type 1 (EBV-1) in periodontal abscesses and the effect of treatment on the subgingival occurrence of these viruses. Eighteen adults with periodontal abscesses participated in the study. Subgingival samples were collected from each patient with sterile curettes from an abscess-affected site and a healthy control site. HCMV and EBV-1 were identified by polymerase chain reaction at the time of the abscess and at 4 months after surgical and systemic doxycycline therapy. HCMV was detected in 66.7% of periodontal abscess sites and in 5.6% of healthy sites (P=0.002). EBV-1 occurred in 72.2% of abscess sites but not in any healthy site (Pabscess sites. Posttreatment, HCMV and EBV-1 were not found in any study site. HCMV and EBV-1 genomes are commonly found in periodontal abscesses. These data favor a model in which a herpesvirus infection of the periodontium impairs the host defense and serves as a platform for the entrance of bacterial pathogens into gingival tissue with subsequent risk of abscess development.

NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors

DEFF Research Database (Denmark)

DeVette, Christa I; Andreatta, Massimo; Bardet, Wilfried

2018-01-01

With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and mainta......With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated...... for evaluating antigen specificity in the murine FVB strain. Our study provides the first detailed molecular and immunoproteomic characterization of the FVB H-2q MHC Class I alleles, including >8500 unique peptide ligands, a multi-allele murine MHC peptide prediction tool, and in vivo validation of these data...

DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ... Show The actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial DNA on murine macrophage

Efficacy of posaconazole in murine experimental sporotrichosis.

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Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

2012-05-01

We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

Irradiation Design for an Experimental Murine Model

International Nuclear Information System (INIS)

Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

2010-01-01

In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

DEFF Research Database (Denmark)

Mikkelsen, J G; Lund, Anders Henrik; Duch, M

1999-01-01

Co-encapsidation of retroviral RNAs into virus particles allows for the generation of recombinant proviruses through events of template switching during reverse transcription. By use of a forced recombination system based on recombinational rescue of replication- defective primer binding site-imp....... We note that recombination-based rescue of primer binding site knock-out retroviral vectors may constitute a sensitive assay to register putative genetic interactions involving endogenous retroviral RNAs present in cells of various species.......-impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...... harbouring the supposed RNA dimer-forming cis -elements and (ii) that copackaged retroviral RNAs can recombine despite pronounced sequence dissimilarity at the cross-over site(s) and within parts of the genome involved in RNA dimerization, encapsidation and strand transferring during reverse transcription...

Cytomegalovirus-induced colonic stricture presenting as acute intestinal obstruction in an immunocompetent adult.

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Dinesh, B V; Selvaraju, Karthikeyan; Kumar, Sampath; Thota, Sumath

2013-09-10

Cytomegalovirus (CMV) infection causes significant morbidty and mortality in immunopromised patients. Though it is usually silent in immunocompetent adults, rarely it can cause serious life-threatening complications. Gastrointestinal tract is one of the commonly involved organs, where it produces a spectrum of clinical manifestation ranging from mild non-specific abdominal pain and diarrhoea to severe infection with toxic megacolon and death. We present a 65-year-old immunocompetent male patient admitted with acute colonic obstruction secondary to CMV-induced colonic stricture, highlighting the importance of considering it as a differential diagnosis for colonic obstruction and reviewing its management.

Pulmonary Hypoplasia Caused by Fetal Ascites in Congenital Cytomegalovirus Infection Despite Fetal Therapy

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Kazumichi Fujioka

2017-11-01

Full Text Available We report two cases of pulmonary hypoplasia due to fetal ascites in symptomatic congenital cytomegalovirus (CMV infections despite fetal therapy. The patients died soon after birth. The pathogenesis of pulmonary hypoplasia in our cases might be thoracic compression due to massive fetal ascites as a result of liver insufficiency. Despite aggressive fetal treatment, including multiple immunoglobulin administration, which was supposed to diminish the pathogenic effects of CMV either by neutralization or immunomodulatory effects, the fetal ascites was uncontrollable. To prevent development of pulmonary hypoplasia in symptomatic congenital CMV infections, further fetal intervention to reduce ascites should be considered.

The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

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Emanuelle Santos de Carvalho Cardoso

2015-04-01

Full Text Available INTRODUCTION: Although urine is considered the gold-standard material for the detection of congenital cytomegalovirus (CMV infection, it can be difficult to obtain in newborns. The aim of this study was to compare the efficiency of detection of congenital CMV infection in saliva and urine samples. METHODS: One thousand newborns were included in the study. Congenital cytomegalovirus deoxyribonucleic acid (DNA was detected by polymerase chain reaction (PCR. RESULTS: Saliva samples were obtained from all the newborns, whereas urine collection was successful in only 333 cases. There was no statistically significant difference between the use of saliva alone or saliva and urine collected simultaneously for the detection of CMV infection. CONCLUSIONS: Saliva samples can be used in large-scale neonatal screening for CMV infection.

Is cytomegalovirus infection related to inflammatory bowel disease, especially steroid-resistant inflammatory bowel disease? A meta-analysis

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Lv Y

2017-12-01

Full Text Available Ya-li Lv, Fei-fei Han, Yang-jie Jia, Zi-rui Wan, Li-li Gong, He Liu, Li-hong Liu Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Human cytomegalovirus (HCMV infection has been associated with inflammatory bowel disease (IBD. Numerous studies have been conducted to analyze the association between HCMV infection and risk of IBD and steroid-resistant IBD, but no clear consensus had been reached. Objectives: The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. Study design: We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they 1 evaluated the association between HCMV infection and IBD disease; 2 evaluated the association between HCMV infection and steroid-resistant IBD disease; 3 were case–control studies or nested case–control studies; 4 provided the numbers (or percentage of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. Results and conclusion: A total of 18 studies including 1,168 patients and 951 health groups was identified, and HCMV infection was distinctly confirmed as a risk factor for the occurrence and development of IBD. When involving 17 studies including 1,306 IBD patients, a total of 52.9% of patients in the cytomegalovirus (CMV-positive groups were observed to have steroid resistance, compared with 30.2% of patients in the CMV-negative groups. There was a significant difference in the risk of steroid resistance between people exposed to HCMV infection and those not exposed HCMV infection in IBD patients. This meta-analysis suggested that HCMV infection is associated with an increased risk for IBD and steroid-resistant IBD. Keywords: cytomegalovirus, infection, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, meta-analysis

Production of antibodies which recognize opiate receptors on murine leukocytes

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Carr, D.J.J.; Bost, K.L.; Blalock, J.E.

1988-01-01

An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, /sup 3/H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with ..beta..-endorphin, meta-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to ..beta..-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

Update on the current status of cytomegalovirus vaccines.

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Sung, Heungsup; Schleiss, Mark R

2010-11-01

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design.

Cytomegalovirus protease targeted prodrug development.

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Sabit, Hairat; Dahan, Arik; Sun, Jing; Provoda, Chester J; Lee, Kyung-Dall; Hilfinger, John H; Amidon, Gordon L

2013-04-01

Human cytomegalovirus (HCMV) is a prevalent virus that infects up to 90% of the population. The goal of this research is to determine if small molecular prodrug substrates can be developed for a specific HCMV encoded protease and thus achieve site-specific activation. HCMV encodes a 256 amino acid serine protease that is responsible for capsid assembly, an essential process for herpes virus production. The esterase activity of the more stable HCMV A143T/A144T protease mutant was evaluated with model p-nitrophenol (ONp) esters, Boc-Xaa-ONp (Ala, Leu, Ile, Val, Gln, Phe at the Xaa position). We demonstrate that the A143T/A144T mutant has esterase activity toward specific small ester compounds, e.g., Boc-L-Ala-ONp. Mono amino acid and dipeptide prodrugs of ganciclovir (GCV) were also synthesized and evaluated for hydrolysis by the A143T/A144T protease mutant in solution. Hydrolysis of these prodrugs was also evaluated in Caco-2 cell homogenates, human liver microsomes (HLMs), and rat and human plasma. For the selectivity potential of the prodrugs, the hydrolysis ratio was evaluated as a percentage of prodrug hydrolyzed by the HCMV protease over the percentages of prodrug hydrolyses by Caco-2 cell homogenates, HLMs, and human/rat plasma. A dipeptide prodrug of ganciclovir, Ac-l-Gln-l-Ala-GCV, emerged as a potential selective prodrug candidate. The results of this research demonstrate that targeting prodrugs for activation by a specific protease encoded by the infectious HCMV pathogen may be achievable.

Trends in the treatment of cytomegalovirus infection in oncohematological patients

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D. N. Balashov

2014-07-01

Full Text Available Cytomegalovirus (CMV-related complications remain an extremely serious and urgent problem in immunocompromised patients. Ganciclovir (GCV is efficient for the treatment of CMV-infection, but myelotoxicity limits the possibilities of their application. In addition, prolonged or intermittent courses of antiviral drugs predispose to the development of CMV drug-resistant strains. Valganciclovir is a safe and effective alternative to intravenous GCV. Despite the well-spread application of effective methods of early detection and pre-emptive treatment, the issue of the control of CMV-infection is not resolved. High intensive immunoablative therapy (alemtuzumab, ATG, еtс. and hematopoietic stem cell transplantation (HSCT from alternative donors greatly increase the risk of life-threatening visceral CMV-infections in patients. Thereby, studies of new therapeutic approaches (for example, transfusion of CMV-specific T-cells are actually in process.

Viral and cellular subnuclear structures in human cytomegalovirus-infected cells.

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Strang, Blair L

2015-02-01

In human cytomegalovirus (HCMV)-infected cells, a dramatic remodelling of the nuclear architecture is linked to the creation, utilization and manipulation of subnuclear structures. This review outlines the involvement of several viral and cellular subnuclear structures in areas of HCMV replication and virus-host interaction that include viral transcription, viral DNA synthesis and the production of DNA-filled viral capsids. The structures discussed include those that promote or impede HCMV replication (such as viral replication compartments and promyelocytic leukaemia nuclear bodies, respectively) and those whose role in the infected cell is unclear (for example, nucleoli and nuclear speckles). Viral and cellular proteins associated with subnuclear structures are also discussed. The data reviewed here highlight advances in our understanding of HCMV biology and emphasize the complexity of HCMV replication and virus-host interactions in the nucleus. © 2015 The Authors.

Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus

DEFF Research Database (Denmark)

Rasmussen, N S; Nielsen, C T; Houen, G

2016-01-01

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse...... and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients...... concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P...

Case of Cytomegalovirus Infection Causing Isolated Oculomotor Nerve Palsy

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Halil Sen

2014-06-01

Full Text Available The third cranial nerve is called the oculomotor nerve. The pathology is revealed by limitation of eye movement inward-up-down, mydriasis, loss of light reflex and ptosis. Oculomotor nerve pathologies are frequently seen in neurology practice and are situations that may be very difficult for differential diagnosis. Differential diagnosis first involves disqualifying intracranial etiologies by imaging because these intracranial etiologies may be situations that can result in death and should be primarily evaluated. If intracranial events are ruled out, generally rarer etiologic reasons with generally difficult differentiation should be researched. Viral infections are among the rare etiological reasons causing 3rd cranial nerve involvement. Our case was a 71-year old female with etiological research due to 3rd cranial nerve palsy. The patient with diabetes-linked immune deficiency was found to have cranial nerve involvement developed secondary to cytomegalovirus (CMV infection. We report this case as 3rd cranial nerve involvement is rarely observed developing linked to CMV infection.

Salivary gland NK cells are phenotypically and functionally unique.

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Marlowe S Tessmer

2011-01-01

Full Text Available Natural killer (NK cells and CD8(+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV. However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment

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Ira Ekmekciu

2017-05-01

Full Text Available There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and

UL36 Rescues Apoptosis Inhibition and In vivo Replication of a Chimeric MCMV Lacking the M36 Gene

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M. Zeeshan Chaudhry

2017-07-01

Full Text Available Apoptosis is an important defense mechanism mounted by the immune system to control virus replication. Hence, cytomegaloviruses (CMV evolved and acquired numerous anti-apoptotic genes. The product of the human CMV (HCMV UL36 gene, pUL36 (also known as vICA, binds to pro-caspase-8, thus inhibiting death-receptor apoptosis and enabling viral replication in differentiated THP-1 cells. In vivo studies of the function of HCMV genes are severely limited due to the strict host specificity of cytomegaloviruses, but CMV orthologues that co-evolved with other species allow the experimental study of CMV biology in vivo. The mouse CMV (MCMV homolog of the UL36 gene is called M36, and its protein product (pM36 is a functional homolog of vICA that binds to murine caspase-8 and inhibits its activation. M36-deficient MCMV is severely growth impaired in macrophages and in vivo. Here we show that pUL36 binds to the murine pro-caspase-8, and that UL36 expression inhibits death-receptor apoptosis in murine cells and can replace M36 to allow MCMV growth in vitro and in vivo. We generated a chimeric MCMV expressing the UL36 ORF sequence instead of the M36 one. The newly generated MCMVUL36 inhibited apoptosis in macrophage lines RAW 264.7, J774A.1, and IC-21 and its growth was rescued to wild type levels. Similarly, growth was rescued in vivo in the liver and spleen, but only partially in the salivary glands of BALB/c and C57BL/6 mice. In conclusion, we determined that an immune-evasive HCMV gene is conserved enough to functionally replace its MCMV counterpart and thus allow its study in an in vivo setting. As UL36 and M36 proteins engage the same molecular host target, our newly developed model can facilitate studies of anti-viral compounds targeting pUL36 in vivo.

[Evaluation of Fusarium spp. pathogenicity in plant and murine models].

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Forero-Reyes, Consuelo M; Alvarado-Fernández, Angela M; Ceballos-Rojas, Ana M; González-Carmona, Lady C; Linares-Linares, Melva Y; Castañeda-Salazar, Rubiela; Pulido-Villamarín, Adriana; Góngora-Medina, Manuel E; Cortés-Vecino, Jesús A; Rodríguez-Bocanegra, María X

The genus Fusarium is widely recognized for its phytopathogenic capacity. However, it has been reported as an opportunistic pathogen in immunocompetent and immunocompromised patients. Thus, it can be considered a microorganism of interest in pathogenicity studies on different hosts. Therefore, this work evaluated the pathogenicity of Fusarium spp. isolates from different origins in plants and animals (murine hosts). Twelve isolates of Fusarium spp. from plants, animal superficial mycoses, and human superficial and systemic mycoses were inoculated in tomato, passion fruit and carnation plants, and in immunocompetent and immunosuppressed BALB/c mice. Pathogenicity tests in plants did not show all the symptoms associated with vascular wilt in the three plant models; however, colonization and necrosis of the vascular bundles, regardless of the species and origin of the isolates, showed the infective potential of Fusarium spp. in different plant species. Moreover, the pathogenicity tests in the murine model revealed behavioral changes. It was noteworthy that only five isolates (different origin and species) caused mortality. Additionally, it was observed that all isolates infected and colonized different organs, regardless of the species and origin of the isolates or host immune status. In contrast, the superficial inoculation test showed no evidence of epidermal injury or colonization. The observed results in plant and murine models suggest the pathogenic potential of Fusarium spp. isolates in different types of hosts. However, further studies on pathogenicity are needed to confirm the multihost capacity of this genus. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Fatal Cytomegalovirus Gastrointestinal Disease in an Infant with Wiskott-Aldrich Syndrome

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Kuan-Ying Huang

2008-01-01

Full Text Available Although most cytomegalovirus (CMV infections are asymptomatic or cause only mild disease, the virus can cause serious disease and even mortality in immunocompromised children. In patients with WiskottAldrich syndrome (WAS, recurrent CMV infection is infrequently seen. A 3-month-old male infant was referred to Chang Gung Children's Hospital due to persistent thrombocytopenia and intermittent tachypnea. WAS complicated with CMV pneumonitis was diagnosed subsequently. He was discharged at the age of 7 months after a complete course of antiviral treatment. Unfortunately, refractory hemorrhagic gastritis developed later and recurred in spite of antiviral treatment and intravenous immunoglobulin. The patient died of recurrent gastrointestinal bleeding at the age of 23 months. This observation indicates that a case of WAS complicated with CMV gastrointestinal disease may need more vigorous treatment.

Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

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Pissuwan, Dakrong; Valenzuela, Stella M.; Killingsworth, Murray C.; Xu, Xiaoda; Cortie, Michael B.

2007-12-01

Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (˜1×105 to 1×1010 W/m2). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5×102 W/m2 being sufficient, provided that a total fluence of ˜30 J/cm2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.

Magnetic resonance imaging of the brain in congenital cytomegalovirus infection

International Nuclear Information System (INIS)

Boesch, C.; Issakainen, J.; Kewitz, G.; Kikinis, R.; Martin, E.; Boltshauser, E.

1989-01-01

The children (age 2 months to 8 years) with a congenital cytomegalovirus (CMV) infection were studied by magnetic resonance imaging (MRI) using a 2.35 Tesla magnet. CMV infection was confirmed by serological investigations and virus culture in the neonatal period. Nine children had severe mental retardation and cerebral palsy, 1 patient suffered from microcephaly, ataxia and deafness. The cranial MRI examination showed the following abnormalities (N): Dilated lateral ventricles (10) and subarachnoid space (8), oligo/pacgyria (8), delayed/pathological myelination (7), paraventricular cysts (6), intra-cerebral calcification (1). This lack of sensitivity for calcification is explainable by the basic principles of MRI. The paraventricular cystic lesions were adjacent ot the occipital horns of the lateral ventricles and separated only by a thin membrane. This finding might represent a 'new sign' for congenital CMV infection in MRI examinations, being characteristic but nevertheless nonspecific, like calcification in CT. (orig.)

Humoral immune-response against human cytomegalovirus (hcmv)-specific proteins after hcmv infection in lung transplantation as detected with recombinant and naturally-occurring proteins

NARCIS (Netherlands)

van Zanten, J; Harmsen, M. C.; van der Giessen, M.; van der Bij, W; Prop, J.; de Leij, L; The, T. Hauw

The humoral immune response to four intracellularly located cytomegalovirus (CMV) proteins was studied in 15 lung transplant recipients experiencing active CMV infections. Five patients had primary infections, and 10 had secondary infections. Antibodies of the immunoglobulin M (IgM) and IgG classes

Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

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Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

2016-01-01

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

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Alejo Efeyan

Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

Science.gov (United States)

Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

2016-01-01

High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection. © 2015 International Society of Neuropathology.

Update on treatment of cytomegalovirus infection in pregnancy and of the newborn with congenital cytomegalovirus.

Science.gov (United States)

Rawlinson, William D; Hamilton, Stuart T; van Zuylen, Wendy J

2016-12-01

The purpose of this review is to assess the recent studies of therapy of pregnant women and neonates, aimed at preventing the consequences of congenital cytomegalovirus (CMV) infection. A recent randomized controlled trial of treatment of CMV during pregnancy with hyperimmune globulin did not show significant efficacy in prevention of foetal infection and morbidity, although there was a trend towards improvement with treatment. Trials of antiviral therapy of the mother during pregnancy have involved small numbers only, confounded by ethical and practical difficulties, and further studies are needed to demonstrate whether or not antivirals are useful and well tolerated in this setting.Antiviral treatment of neonatal CMV acquired congenitally has been studied in well controlled trials and the antiviral valganciclovir has shown efficacy in reducing the more severe outcomes. Trials are ongoing of the use of antivirals in less severe disease, although results are likely to take several years. Congenital CMV infection is the most frequent cause of congenital malformation in developed countries, with a symptomatic prevalence of 0.64% of all live births. Infection may result in neurodevelopmental delay, foetal or neonatal death, and most frequently, sensorineural hearing loss. Successful control of viral infections during pregnancy and in the newborn period is essential in reducing early and late morbidity and mortality. Control of congenital CMV infection may be via primary prevention methods such as reducing contact with the pathogen, improved hygiene - both for the pregnant mother and for the neonate, or secondary prevention via reduction of vertical transmission from mother to foetus and reduction in consequences of infection by treatment of infected pregnant women and infected neonates.

Comparison of real-time and quantitative polymerase chain reaction assays in detection of cytomegalovirus DNA in clinical specimens

International Nuclear Information System (INIS)

Gokahmetoglu, S.; Deniz, E.

2007-01-01

To compare the real-time (RT) and qualitative (Q) polymerase chain reaction (PCR) assays for detection of Cytomegalovirus (CMV) DNA. The study took place in the Department of Microbiology, Erciyes University, Kayseri and in Iontek Laboratory, Istanbul, Turkey, from August to December 2006. One hundred and seven clinical specimens from 67 patients were included in the study. Cytomegalovirus DNA was investigated using RT-PCR kit (Fluorion Iontek, Turkey) and Q-PCR kit (Fluorion Iontek, Turkey). Deoxyribonucleic acid sequencing was applied to the samples that yielded discrepant results in both assays. Mac Nema's Chi Square test was used for statistical analysis. Of the specimens, 27 were found positive with both assays: 9 with only RT-PCR, and 11 with only Q-PCR assay. Both assays were found negative in 60 of the specimens. There was a good agreement between the 2 assays in 87(81.3%) of the specimens. There was no statistical significant difference between the assays (p>0.05). Two of the 11 samples that RT-PCR negative Q-PCR positive, and 3 of 9 samples that RT-PCR positive Q-PCR negative were found to be CMV DNA positive by DNA sequencing. A good level of concordance between RT-PCR and Q-PCR assays for CMV DNA detection has been found. (author)

Biological markers as predictors of radiosensitivity in syngeneic murine tumors

International Nuclear Information System (INIS)

Chang, Sei Kyung; Shin, Hyun Soo; Seong, Jin Sil; Kim, Sung Hee

2006-01-01

We investigated whether a relationship exists between tumor control dose 50 (TCD 50 ) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD 50 , TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 ∼ 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD 50 , TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21 WAF1/CIP1 , BAX, Bcl-2, Bcl-x L , Bcl-x S , and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD 50 or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD 50 , TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, ρ = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD 50 (ρ = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21 WAF1/CIP1 and p34 showed a significant correlation either with TCD 50 (R = 0.893, ρ = 0.041 and R = 0.904, ρ = 0.035) or with TGD (R = -0.922, ρ 0.026 and R = -0.890, ρ = 0.043). The tumors with high constitutive expression levels of p21 WAF1/CIP1 or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of p21 WAF1/CIP1 or p34 can be used as biological

Biological markers as predictors of radiosensitivity in syngeneic murine tumors

Energy Technology Data Exchange (ETDEWEB)

Chang, Sei Kyung; Shin, Hyun Soo [Bundang CHA General Hospital, Seongnam (Korea, Republic of); Seong, Jin Sil; Kim, Sung Hee [Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2006-06-15

We investigated whether a relationship exists between tumor control dose 50 (TCD{sub 50}) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD{sub 50}, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 {approx} 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD{sub 50}, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21{sup WAF1/CIP1}, BAX, Bcl-2, Bcl-x{sub L}, Bcl-x{sub S}, and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD{sub 50} or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD{sub 50}, TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, {rho} = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD{sub 50} ({rho} = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21{sup WAF1/CIP1} and p34 showed a significant correlation either with TCD{sub 50} (R = 0.893, {rho} = 0.041 and R = 0.904, {rho} = 0.035) or with TGD (R = -0.922, {rho} 0.026 and R = -0.890, {rho} = 0.043). The tumors with high constitutive expression levels of p21{sup WAF1/CIP1} or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The

A young patient with multisystem complications after cytomegalovirus infection

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Swaroopa Pulivarthi

2014-01-01

Full Text Available We are describing a case of an 18-year-old male patient with cytomegalovirus (CMV associated guillain-barre syndrome (GBS who presented with an acute onset of generalized weakness and numbness in the extremities, dysphagia, and facial diplegia, followed by respiratory failure, which led to mechanical ventilation. He had positive immunoglobulin G and immunoglobulin M antibodies against CMV, and CMV polymerase chain reaction was positive with <2000 copies of deoxyribonucleic acid. Human immunodeficiency virus test was negative. He received a course of ganciclovir, intravenous immunoglobulin, and plasmapheresis. After improving from acute episode, patient was transferred to a rehabilitation facility for physical and occupational therapy. At the rehabilitation facility, he exhibited signs of acute abdomen with pain in the left upper quadrant secondary to peritonitis from dislodged gastrostomy tube and underwent exploratory laparotomy. During the hospital course he was found to have splenic infarct and colitis on the computed tomography of abdomen. This case showed an immunocompetent young patient with multisystem complications including guillain-barre syndrome (GBS, splenic infarct, hepatitis, and colitis due to CMV.

Characterization of the binding of radioiodinated hybrid recombinant IFN-alpha A/D to murine and human lymphoid cell lines

International Nuclear Information System (INIS)

Faltynek, C.R.; Princler, G.L.; Schwabe, M.; Shata, M.T.; Lewis, G.K.; Kamin-Lewis, R.M.

1990-01-01

The hybrid recombinant human interferon (IFN) rIFN-alpha A/D was radioiodinated. Specific binding of [125I]rIFN-alpha A/D was observed with both human and murine cell lines. The binding of [125I]rIFN-alpha A/D to human Daudi cells had similar characteristics to the previously described binding of [125I]rIFN-alpha A or -alpha 2. The following lines of evidence demonstrated that [125I]rIFN-alpha A/D bound with high affinity to the same receptor on murine cells as murine IFN-alpha and -beta: (i) the binding of [125I]rIFN-alpha A/D to murine LBRM cells was inhibited to a similar extent by natural murine IFN-alpha, natural murine IFN-beta, and rIFN-A/D; (ii) the Kd (approximately 2 X 10(-10) M) obtained from both competition experiments and saturation binding experiments with [125I]rIFN-alpha A/D was comparable to the previously reported Kd for the binding of natural murine IFN-alpha and -beta to other murine cell lines; (iii) the size of the cross-linked [125I]rIFN-alpha A/D receptor complex formed on murine LBRM cells was similar to the previously reported cross-linked complex formed after binding radioiodinated natural murine IFN-beta to other murine cell lines. Due to the current lack of readily available recombinant murine IFN-alpha or -beta for radiolabeling and the previously demonstrated biological activity of rIFN-alpha A/D on murine cells, [125I]rIFN-alpha A/D should prove to be a useful reagent for further studies of murine IFN receptors

Comparison of the Histopaque-1119 method with the Plasmagel method for separation of blood leukocytes for cytomegalovirus isolation.

OpenAIRE

Slifkin, M; Cumbie, R

1992-01-01

Histopaque-1119 (Sigma Chemical Co., St. Louis, Mo.) and Plasmagel (Cellular Products, Inc., Buffalo, N.Y.) were compared as density gradient separation reagents for the separation of polymorphonuclear leukocytes and mononuclear cells from blood from the isolation of cytomegalovirus (CMV). Of 200 peripheral blood specimens examined, CMV was recovered from 51 by both methods. The time of detection of immunofluorescent sites or a cytopathic effect associated with CMV was similar by each method....

Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor

International Nuclear Information System (INIS)

Gough, N.M.; Gearing, D.P.; King, J.A.; Willson, T.A.; Hilton, D.J.; Nicola, N.A.; Metcalf, D.

1988-01-01

A human homologue of the recently cloned murine leukemia-inhibitory factor (LIF) gene was isolated from a genomic library by using the marine cDNA as a hybridization probe. The nucleotide sequence of the human gene indicated that human LIF has 78% amino acid sequence identity with murine LIF, with no insertions or deletions, and that the region of the human gene encoding the mature protein has one intervening sequence. After oligonucleotide-mediated mutagenesis, the mature protein-coding region of the LIF gene was introduced into the yeast expression vector YEpsec1. Yeast cells transformed with the resulting recombinant could be induced with galactose to produce high levels of a factor that induced the differentiation of murine M1 leukemic cells in a manner analogous to murine LIF. This factor competed with 125 I-labeled native murine LIF for binding to specific cellular receptors on murine cells, compatible with a high degree of structural similarity between the murine and human factors

Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

Science.gov (United States)

Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

1992-05-15

A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.

Noncanonical microRNAs and endogenous siRNAs in lytic infection of murine gammaherpesvirus.

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Jing Xia

Full Text Available MicroRNA (miRNA and endogenous small interfering RNA (endo-siRNA are two essential classes of small noncoding RNAs (sncRNAs in eukaryotes. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNA biogenesis pathway. In order to identify noncanonical miRNAs and endo-siRNAs responding to virus infection and study their potential function, we sequenced small-RNA species from cells lytically infected with murine gammaherpesvirus 68 (MHV68. In addition to three novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonical miRNAs, including miRNAs derived from transfer RNAs, small nucleolar RNAs and introns, in the host were identified. These noncanonical miRNAs exhibited features distinct from that of canonical miRNAs in lengths of hairpins, base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. Besides several known murine endo-siRNAs detected by the sequencing profiling, a novel locus in the mouse genome was identified to produce endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs. Unexpectedly, the SINE-derived endo-siRNAs were found in a variety of sequencing data and virus-infected cells. Moreover, a murine miRNA was up-regulated more than 35 fold in infected than in mock-treated cells. The putative targets of the viral and the up-regulated murine miRNAs were potentially involved in processes of gene transcription and protein phosphorylation, and localized to membranes, suggesting their potential role in manipulating the host basal immune system during lytic infection. Our results extended the number of noncanonical miRNAs in mammals and shed new light on their potential functions of lytic infection of MHV68.

The murine Cd48 gene: allelic polymorphism in the IgV-like region.

Science.gov (United States)

Cabrero, J G; Freeman, G J; Reiser, H

1998-12-01

The murine CD48 molecule is a member of the immunoglobulin superfamily which regulates the activation of T lymphocytes. prior cloning experiments using mRNA from two different mouse strains had yielded discrepant sequences within the IgV-like domain of murine CD48. To resolve this issue, we have directly sequenced genomic DNA of 10 laboratory strains and two inbred strains of wild origin. The results of our analysis reveal an allelic polymorphism within the IgV-like domain of murine CD48.

Scanning electron microscopy of the neuropathology of murine cerebral malaria

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Brenneis Christian

2006-11-01

Full Text Available Abstract Background The mechanisms leading to death and functional impairments due to cerebral malaria (CM are yet not fully understood. Most of the knowledge about the pathomechanisms of CM originates from studies in animal models. Though extensive histopathological studies of the murine brain during CM are existing, alterations have not been visualized by scanning electron microscopy (SEM so far. The present study investigates the neuropathological features of murine CM by applying SEM. Methods C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. When typical symptoms of CM developed perfused brains were processed for SEM or light microscopy, respectively. Results Ultrastructural hallmarks were disruption of vessel walls, parenchymal haemorrhage, leukocyte sequestration to the endothelium, and diapedesis of macrophages and lymphocytes into the Virchow-Robin space. Villous appearance of observed lymphocytes were indicative of activated state. Cerebral oedema was evidenced by enlargement of perivascular spaces. Conclusion The results of the present study corroborate the current understanding of CM pathophysiology, further support the prominent role of the local immune system in the neuropathology of CM and might expose new perspectives for further interventional studies.

Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

Energy Technology Data Exchange (ETDEWEB)

Pissuwan, Dakrong [University of Technology Sydney, Institute for Nanoscale Technology (Australia); Valenzuela, Stella M. [University of Technology Sydney, Department of Medical and Molecular Biosciences (Australia)], E-mail: stella.valenzuela@uts.edu.au; Killingsworth, Murray C. [Sydney South West Pathology Service (Australia)], E-mail: murray.killingsworth@swsahs.nsw.gov.au; Xu, Xiaoda; Cortie, Michael B. [University of Technology Sydney, Institute for Nanoscale Technology (Australia)], E-mail: michael.cortie@uts.edu.au

2007-12-15

Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation ({approx}1x10{sup 5} to 1x10{sup 10} W/m{sup 2}). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5x10{sup 2} W/m{sup 2} being sufficient, provided that a total fluence of {approx}30 J/cm{sup 2} is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm{sup 2} resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.

Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

International Nuclear Information System (INIS)

Pissuwan, Dakrong; Valenzuela, Stella M.; Killingsworth, Murray C.; Xu, Xiaoda; Cortie, Michael B.

2007-01-01

Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (∼1x10 5 to 1x10 10 W/m 2 ). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5x10 2 W/m 2 being sufficient, provided that a total fluence of ∼30 J/cm 2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm 2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells

Analysis of the capacity to produce IL-3 in murine AIDS

DEFF Research Database (Denmark)

Neuenschwander, A U; Marker, O; Thomsen, Allan Randrup

1994-01-01

Adult C57BL/6 mice infected with LP-BM5 murine leukaemia virus represent a model of murine AIDS (MAIDS). In this study we have analysed the capacity of CD4+ T cells from infected mice to produce IL-3 following stimulation with ConA for 24-72 h. In contrast to the position with IL-2, the production...

Increased seroprevalence of IgG-class antibodies against cytomegalovirus, parvovirus B19, and varicella-zoster virus in women working in child day care

NARCIS (Netherlands)

van Rijckevorsel, Gini G. C.; Bovee, Lian P. M. J.; Damen, Marjolein; Sonder, Gerard J. B.; Schim van der Loeff, Maarten F.; van den Hoek, Anneke

2012-01-01

Background: Primary maternal infection with cytomegalovirus (CMV), parvovirus B19 (B19V), and varicella-zoster virus (VZV) may result in adverse pregnancy outcomes like congenital infection or foetal loss. Women working in child day care have an increased exposure to CMV, B19V, and VZV. By comparing

Characterisation of Neutropenia-Associated Neutrophil Elastase Mutations in a Murine Differentiation Model In Vitro and In Vivo.

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Michael Wiesmeier

Full Text Available Severe congenital neutropenia (SCN is characterised by a differentiation block in the bone marrow and low neutrophil numbers in the peripheral blood, which correlates with increased risk of bacterial infections. Several underlying gene defects have been identified in SCN patients. Mutations in the neutrophil elastase (ELANE gene are frequently found in SCN and cyclic neutropenia. Both mislocalization and misfolding of mutant neutrophil elastase protein resulting in ER stress and subsequent induction of the unfolded protein response (UPR have been proposed to be responsible for neutrophil survival and maturation defects. However, the detailed molecular mechanisms still remain unclear, in part due to the lack of appropriate in vitro and in vivo models. Here we used a system of neutrophil differentiation from immortalised progenitor lines by conditional expression of Hoxb8, permitting the generation of mature near-primary neutrophils in vitro and in vivo. NE-deficient Hoxb8 progenitors were reconstituted with murine and human forms of typical NE mutants representative of SCN and cyclic neutropenia, and differentiation of the cells was analysed in vitro and in vivo. ER stress induction by NE mutations could be recapitulated during neutrophil differentiation in all NE mutant-reconstituted Hoxb8 cells. Despite ER stress induction, no change in survival, maturation or function of differentiating cells expressing either murine or human NE mutants was observed. Further analysis of in vivo differentiation of Hoxb8 cells in a murine model of adoptive transfer did not reveal any defects in survival or differentiation in the mouse. Although the Hoxb8 system has been found to be useful for dissection of defects in neutrophil development, our findings indicate that the use of murine systems for analysis of NE-mutation-associated pathogenesis is complicated by differences between humans and mice in the physiology of granulopoiesis, which may go beyond possible

Murine models of H. pylori-induced gastritis and gastric adenocarcinoma.

Science.gov (United States)

Krueger, Sabine; Roessner, Albert; Kuester, Doerthe

2011-10-15

Laboratory mice have become one of the best animal species for mechanistic studies in gastrointestinal research. Their abundant genetic information, the way of causing carcinogenesis easily by transgenic and gene knockout techniques, limited effort in time and costs, and their practicability provide advantages over other animal models. Meanwhile, several murine practical models have been established for the investigation of the initiation, expansion, and progression of gastritis and gastric carcinoma, for assessing the effects of bacterial, genetic and environmental factors, and for evaluating therapeutic and preventive strategies in gastric diseases. This article gives a review of murine models of gastritis and gastric cancer, placing emphasis on the models associated with Helicobacter pylori infection and techniques used in our laboratory. We discuss matters of murine gastric anatomy, as well as techniques of infection, tissue preparation, and histology. Copyright © 2011 Elsevier GmbH. All rights reserved.

The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

Energy Technology Data Exchange (ETDEWEB)

Nemčovičová, Ivana [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States); Slovak Academy of Sciences, Dúbravská cesta 9, SK 84505 Bratislava (Slovakia); Zajonc, Dirk M., E-mail: dzajonc@liai.org [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States)

2014-03-01

The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X{sub 6}G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host�

The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

International Nuclear Information System (INIS)

Nemčovičová, Ivana; Zajonc, Dirk M.

2014-01-01

The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X 6 G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host–receptor interactions

Refractory ulcerative colitis complicated by cytomegalovirus infection successfully treated with valganciclovir

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Tiziana Larussa

2012-11-01

Full Text Available Cytomegalovirus (CMV infection is widespread in the general population. In patients with severe and/or steroid-refractory ulcerative colitis (UC, local reactivation of CMV can be detected in actively inflamed colonic tissue in approximately 30% of cases. However, the role of CMV in patients with UC is not clearly understood. There is evidence to show a possible role in exacerbating a colitis flare, whereas other studies describe CMV as an innocent bystander. We report the case of a patient with severe UC complicated by CMV infection who did not respond to conventional therapy. A complete diagnostic panel for CMV diagnosis, including tissue polymerase chain reaction and immunohistochemistry, was carried out. Three-week therapy with oral valganciclovir resulted in dramatic clinical and endoscopic improvement. Timing of diagnosis and treatment of CMV infection complicating UC is crucial in order to recognize the organ-disease and plan appropriate treatment.

Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression

International Nuclear Information System (INIS)

Hoever, Gerold; Vogel, Jens-Uwe; Lukashenko, Polina; Hofmann, Wolf-Karsten; Komor, Martina; Doerr, Hans Wilhelm; Cinatl, Jindrich

2005-01-01

In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies

Infección congénita por citomegalovirus en recién nacidos del estado de San Luis Potosí, México Congenital cytomegalovirus infection in newborn infants from the state of San Luis Potosí, Mexico

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Daniel E Noyola

2011-12-01

Full Text Available OBJETIVO: Determinar la prevalencia de infección congénita por citomegalovirus en recién nacidos participantes en el programa de tamiz neonatal de los Servicios de Salud de San Luis Potosí. MATERIAL Y MÉTODOS: Se evaluó la presencia de citomegalovirus en muestras de sangre almacenadas en papel filtro. RESULTADOS. Se detectó la presencia de citomegalovirus en 10 (0.68% de 1 457 muestras estudiadas. No se encontraron diferencias en las características de los recién nacidos con infección congénita en comparación con aquéllos sin infección. CONCLUSIONES: Es necesario concientizar a los profesionales de la salud sobre la prevalencia e impacto de la infección congénita por citomegalovirus.OBJECTIVE: To determine the prevalence of congenital cytomegalovirus infection in newborn infants included in the neonatal screening program coordinated by the State Health Services in San Luis Potosí. MATERIAL AND METHODS: We evaluated the presence of cytomegalovirus in blood samples stored in filter paper. RESULTS: Cytomegalovirus was detected in 10 (0.68% of the 1 457 samples included in the study. There were no differences in the characteristics of infants with congenital infection compared to those without infection. CONCLUSIONS: It is necessary to increase awareness of health professionals regarding the prevalence and impact of congenital cytomegalovirus infection.

Acute Febrile Illness and Complications Due to Murine Typhus, Texas, USA1,2.

Science.gov (United States)

Afzal, Zeeshan; Kallumadanda, Sunand; Wang, Feng; Hemmige, Vagish; Musher, Daniel

2017-08-01

Murine typhus occurs relatively commonly in southern Texas, as well as in California. We reviewed records of 90 adults and children in whom murine typhus was diagnosed during a 3-year period in 2 hospitals in southern Texas, USA. Most patients lacked notable comorbidities; all were immunocompetent. Initial signs and symptoms included fever (99%), malaise (82%), headache (77%), fatigue (70%), myalgias (68%), and rash (39%). Complications, often severe, in 28% of patients included bronchiolitis, pneumonia, meningitis, septic shock, cholecystitis, pancreatitis, myositis, and rhabdomyolysis; the last 3 are previously unreported in murine typhus. Low serum albumin and elevated procalcitonin, consistent with bacterial sepsis, were observed in >70% of cases. Rash was more common in children; thrombocytopenia, hyponatremia, elevated hepatic transaminases, and complications were more frequent in adults. Murine typhus should be considered as a diagnostic possibility in cases of acute febrile illness in southern and even in more northern US states.

Concepts for treatment of micrometastases developed in murine systems

International Nuclear Information System (INIS)

Schabel, F.M. Jr.

1976-01-01

Current knowledge of tumor cell population growth kinetics indicates that the growth fraction (viable tumor cells undergoing active cell replication) is inversely related to population size. Tumor cells in micrometastases should, therefore, be more sensitive to anticancer drugs active against anabolizing cells than are tumor cells in the larger, grossly apparent primary tumor from which they were derived. This indicates the probability that micrometastases will be effectively responsive to more drugs than is the primary and clinically apparent tumor from which they came. Studies with at least four metastatic and uniformly fatal murine solid tumors (lung, breast, colon, and melanoma) have demonstrated significantly improved cure rates with drug treatment following surgical removal of the grossly apparent primary tumor than can be obtained with either surgery or drug treatment when used alone. Further, both disease staging and drug dosage have been shown to influence cure rates of combined-modality treatment. With several mouse tumors, a significantly smaller number of viable tumor cells can establish lethal tumors in the presence of radiation-inactivated tumor cells than in their absence. This suggests that small numbers of residual viable tumor cells in radiation-treated tumor sites may be a greater threat to clinical cure than smaller tumor cell populations remaining in situ after surgery

Effects of murine and human bone marrow-derived mesenchymal stem cells on cuprizone induced demyelination.

Directory of Open Access Journals (Sweden)

Jasmin Nessler

Full Text Available For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE, an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS. In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.

Detection of human cytomegalovirus and Epstein-Barr virus in symptomatic and asymptomatic apical periodontitis lesions by real-time PCR

OpenAIRE

Ozbek, Selcuk M.; Ozbek, Ahmet; Yavuz, Muhammed Selim

2013-01-01

Objectives: Recent studies have investigated the occurrence of human cytomegalovirus and Epstein-Barr Virus in samples from apical periodontitis lesions and a role in the pathogenesis of this disease has been suggested. Because genotype distribution and seroprevalence of EBV and HCMV differ among populations, it is important to determine the presence of these viruses in endodontic periapical lesions of different populations. The aims of this study were to determine the presence of HCMV and EB...

Reemergence of Murine Typhus in the US

Centers for Disease Control (CDC) Podcasts

2015-04-21

Dr. Lucas Blanton discusses the Reemergence of Murine Typhus in Galveston Texas in 2013.  Created: 4/21/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/27/2015.

Three-dimensional in vivo imaging of the murine liver: a micro-computed tomography-based anatomical study.

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Teresa Fiebig

Full Text Available Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver.

Immune senescence: relative contributions of age and cytomegalovirus infection.

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Andrea Mekker

Full Text Available Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV infection with or without thymectomy (Tx alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8(+ T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any 'de novo' immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence.

Systemic effects induced by the venom of the snake Bothrops caribbaeus in a murine model.

Science.gov (United States)

Herrera, Cristina; Rucavado, Alexandra; Warrell, David A; Gutiérrez, José María

2013-03-01

Snakebite envenoming by Bothrops caribbaeus, an endemic viperid from the Lesser Antillean island of Saint Lucia, is clinically characterized by local tissue damage and systemic thrombosis that can lead to cerebral, myocardial or pulmonary infarctions and venous thromboses. Systemic effects (lethality, pulmonary hemorrhage, thrombocytopenia and coagulopathy) induced by intravenous (i.v.) administration of B. caribbaeus venom were studied in mice. The role of snake venom metalloproteinases (SVMPs) in these systemic alterations was assessed by inhibition with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa(2)EDTA). A snake C-type lectin-like (snaclec) and a type P-III hemorrhagic SVMP were isolated and characterized from this venom, and the effect of venom and the isolated snaclec on human platelet aggregation was studied in vitro. Results indicate that SVMPs play an important role in the overall toxicity of B. caribbaeus venom, being responsible for systemic hemorrhage and lethality, but not thrombocytopenia, whereas the isolated snaclec is involved in the thrombocytopenic effect. Both venom and snaclec induce platelet aggregation/agglutination. Moreover, the snaclec binds directly to glycoprotein Ib (GPIb) and induces agglutination in washed fixed platelets. On the other hand, B. caribbaeus venom hydrolyzed fibrinogen in vitro and induced a partial drop of fibrinogen levels with an increase in fibrin/fibrinogen degradation products (FDP) levels in vivo. The negative result for D-dimer (DD) in plasma is consistent with the lack of microscopic evidence of pulmonary thrombosis and endothelial cell damage. Likewise, no increments in plasma sE-selectin levels were detected. The absence of thrombosis in this murine model suggests that this effect may be species-specific. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pasteurization of breastmilk decreases the rate of postnatally acquired cytomegalovirus infections, but shows a nonsignificant trend to an increased rate of necrotizing enterocolitis in very preterm infants--a preliminary study.

Science.gov (United States)

Stock, Katharina; Griesmaier, Elke; Brunner, Barbara; Neubauer, Vera; Kiechl-Kohlendorfer, Ursula; Trawöger, Rudolf

2015-03-01

This study assessed whether feeding preterm infants unpasteurized breastmilk (1) decreases the rate of late-onset sepsis and necrotizing enterocolitis and (2) increases the rate of postnatally acquired cytomegalovirus infections. Between January 2008 and July 2013, preterm infants below 32 completed weeks of gestational age admitted to the neonatal intensive care unit of Innsbruck Medical University (Innsbruck, Austria) (n=344) were eligible for the study. Of those, 323 fed breastmilk were retrospectively enrolled in the study. Two groups were formed, with 164 infants being fed unpasteurized and 159 infants being fed pasteurized breastmilk. There was no significant difference in the rate of late-onset sepsis or necrotizing enterocolitis between the unpasteurized and pasteurized breastmilk groups (late-onset sepsis, 15.9% versus 15.1% [p=0.486]; necrotizing enterocolitis, 2.4% versus 4.4% [p=0.254]). The number of infants diagnosed with postnatally acquired cytomegalovirus infection was significantly higher in the unpasteurized group (39.3%) compared with the pasteurized group (4.2%) (p=0.008). Feeding preterm infants unpasteurized breastmilk increases the rate of postnatally acquired cytomegalovirus infections. However, we also demonstrate a nonsignificant trend to a decreased rate of necrotizing enterocolitis in the unpasteurized group, which needs to be confirmed in larger studies.

Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

OpenAIRE

Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

1997-01-01

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with ...

Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial

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Michele Gerber

2013-09-01

Full Text Available 2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB and phosphoprotein 65 (pp65 formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV+ recipients of an allogeneic hematopoietic stem cell transplant (HCT. A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV+ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.

Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial.

Science.gov (United States)

Smith, Larry R; Wloch, Mary K; Chaplin, Jennifer A; Gerber, Michele; Rolland, Alain P

2013-09-25

2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine's planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV⁺) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV⁺ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.

False positive immunoglobulin m antibody to cytomegalovirus in child with infectious mononucleosis caused by epstein-barr virus infection.

Science.gov (United States)

Park, Jee Min; Shin, Jae Il; Lee, Jae Seung; Jang, Young Ho; Kim, Sung Hun; Lee, Kang Hyuk; Lee, Chang Hoon

2009-10-31

A 16-month-old boy was admitted because of cough that had lasted for 10 days. The patient showed severe hepatomegaly incidentally, and dual positivity of Immunoglobulin (Ig) M to Epstein-Barr virus (EBV) viral capsid antigen (VCA) and cytomegalovirus (CMV). On the basis of seroconversion to Epstein-Barr nuclear antigen (EBNA) Ig G positivity and reduced CMV Ig M titer with persistently negative CMV Ig G, a definite diagnosis of EBV-induced infectious mononucleosis was established 1 year 2 month later.

Specific interactions between transcription factors and the promoter-regulatory region of the human cytomegalovirus major immediate-early gene

International Nuclear Information System (INIS)

Ghazal, P.; Lubon, H.; Hennighausen, L.

1988-01-01

Repeat sequence motifs as well as unique sequences between nucleotides -150 and -22 of the human cytomegalovirus immediate-early 1 gene interact in vitro with nuclear proteins. The authors show that a transcriptional element between nucleotides -91 and -65 stimulated promoter activity in vivo and in vitro by binding specific cellular transcription factors. Finally, a common sequence motif, (T)TGG/AC, present in 15 of the determined binding sites suggests a particular class of nuclear factors associated with the immediate-early 1 gene

Interactions Between the Cytomegalovirus Promoter and the Estrogen Response Element: Implications for Design of Estrogen-Responsive Reporter Plasmids

OpenAIRE

Derecka, K.; Wang, C.K.; Flint, A.P.F.

2006-01-01

We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)...

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

OpenAIRE

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initia...

Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells

DEFF Research Database (Denmark)

Fornara, O; Bartek, J; Rahbar, A

2016-01-01

Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express...... human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary...... GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co...

Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV Pentameric Complex Proteins GP129, 131 and 133

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Josephine S. Gnanandarajah

2014-02-01

Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus (HCMV is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV, consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model.

Rhabdomyolysis associated with cytomegalovirus infection in kidney transplant recipients.

Science.gov (United States)

Jung, H-Y; Kim, K-H; Park, S-C; Lee, J-H; Choi, J-Y; Cho, J-H; Park, S-H; Kim, Y-L; Kim, H-K; Huh, S; Kim, C-D

2014-12-01

Rhabdomyolysis is a pathological syndrome caused by skeletal muscle cell damage that affects the integrity of the cellular membrane and leads to the release of toxic intracellular constituents into the bloodstream. Although cytomegalovirus (CMV) has rarely been reported as a cause of rhabdomyolysis, CMV infection could be considered as a possible cause because of its clinical significance in kidney transplant recipients (KTRs). We report 2 cases of rhabdomyolysis associated with CMV infection in KTRs. A 64-year-old woman (Case 1) and a 65-year-old man (Case 2), who had each received a kidney from a living unrelated donor, were admitted with complaints of weakness in both legs and myalgia. Laboratory findings revealed highly increased creatine phosphokinase and myoglobinuria. In both cases, no recent alterations of medications had occurred, and other causes of rhabdomyolysis--such as trauma, alcohol, drugs, and electrolyte abnormalities - were excluded. CMV pp65 antigen was positive, and patients were diagnosed with rhabdomyolysis associated with CMV infection. Both patients recovered without complications after ganciclovir treatment. In conclusion, CMV infection should be considered as a possible cause of rhabdomyolysis in KTRs. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Women's attitudes toward practicing cytomegalovirus prevention behaviors

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Rosemary Thackeray

2016-12-01

Full Text Available Congenital cytomegalovirus (CMV infection causes severe disabilities and developmental delays. Women's awareness of CMV is low. Only about half of healthcare providers report counseling women about behaviors to reduce CMV risk and public health education is limited. Routine CMV counseling is not recommend. Providers may lack time to counsel women; other conditions may take priority for counseling; there may be a perception that women are reluctant to follow advice. This cross-sectional descriptive study examined women's attitudes toward CMV prevention behaviors. Data were collected from an online panel of 840 U.S. women 18–40 years of age, who had a child <5 years of age, and were pregnant or planning a pregnancy in the next 12 months. Questions assessed CMV awareness, frequency of past behaviors that transmit CMV, and attitudes toward eight CMV prevention behaviors. Only 15.5% of women were somewhat or very familiar with CMV. Very few women (6.1% reported hearing from their provider about CMV. Women held positive attitudes toward the CMV prevention behaviors and perceived them as feasible. Least positive attitudes were toward not kissing a child on the lips and not sharing foods. Predictors of positive attitudes were CMV awareness, past behavior, talking to a healthcare provider, and perceived risk reduction. Healthcare providers and public health practitioners should collaborate to increase CMV awareness. Encouraging behaviors to reduce saliva sharing may result in greater gains in reducing CMV infection.

Characteristics of Cytomegalovirus Uveitis in Immunocompetent Patients.

Science.gov (United States)

Woo, Jyh Haur; Lim, Wee K; Ho, Su L; Teoh, Stephen C

2015-01-01

To present the clinical characteristics of patients with anterior uveitis who had evidence of cytomegalovirus (CMV) infection on polymerase chain reaction PCR-based assays for viral DNA in aqueous samples. This was a retrospective observational case series of 16 patients with CMV infection on qualitative polymerase chain reaction PCR-based assays for viral DNA in aqueous samples. Case records of 16 patients were reviewed and relevant clinical information was collected using a standardized data sheet. There were 10 male and 6 female patients, with 16 eyes included. The median age at the first attack was 52 years (range 27-77 years). Thirteen patients (81.3%) presented with an initial BCVA of 20/40 or better. Eleven eyes (68.8%) had anterior chamber inflammation of 1+ cells or less. Eight eyes (50.0%) had concomitant sectoral iris atrophy, while 2 eyes were noted to have heterochromic irides. Eleven patients (68.8%) presented with an elevated intraocular pressure. Seven patients (43.8%) had clinical features that led to a presumptive diagnosis of Posner-Schlossman syndrome, while 3 patients (18.8%) were initially diagnosed with Fuchs heterochromic iridocyclitis. Six patients were initially treated for uveitic glaucoma or anterior uveitis of unknown cause. There is a spectrum of clinical manifestations of CMV anterior uveitis. A high index of suspicion of a possible viral etiology, especially CMV, and subsequent accurate identification of the virus involved are fundamental to the overall therapeutic approach.

Differentiation of minute virus of mice and mouse parvovirus by high resolution melting curve analysis.

Science.gov (United States)

Rao, Dan; Wu, Miaoli; Wang, Jing; Yuan, Wen; Zhu, Yujun; Cong, Feng; Xu, Fengjiao; Lian, Yuexiao; Huang, Bihong; Wu, Qiwen; Chen, Meili; Zhang, Yu; Huang, Ren; Guo, Pengju

2017-12-01

Murine parvovirus is one of the most prevalent infectious pathogens in mouse colonies. A specific primer pair targeting the VP2 gene of minute virus of mice (MVM) and mouse parvovirus (MPV) was utilized for high resolution melting (HRM) analysis. The resulting melting curves could distinguish these two virus strains and there was no detectable amplification of the other mouse pathogens which included rat parvovirus (KRV), ectromelia virus (ECT), mouse adenovirus (MAD), mouse cytomegalovirus (MCMV), polyoma virus (Poly), Helicobactor hepaticus (H. hepaticus) and Salmonella typhimurium (S. typhimurium). The detection limit of the standard was 10 copies/μL. This study showed that the PCR-HRM assay could be an alternative useful method with high specificity and sensitivity for differentiating murine parvovirus strains MVM and MPV. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units

International Nuclear Information System (INIS)

Kuegler, S.; Lingor, P.; Schoell, U.; Zolotukhin, S.; Baehr, M.

2003-01-01

Adeno-associated- (AAV) based vectors are promising tools for gene therapy applications in several organs, including the brain, but are limited by their small genome size. Two short promoters, the human synapsin 1 gene promoter (hSYN) and the murine cytomegalovirus immediate early promoter (mCMV), were evaluated in bicistronic AAV-2 vectors for their expression profiles in cultured primary brain cells and in the rat brain. Whereas transgene expression from the hSYN promoter was exclusively neuronal, the murine CMV promoter targeted expression mainly to astrocytes in vitro and showed weak transgene expression in vivo in retinal and cortical neurons, but strong expression in thalamic neurons. We propose that neuron specific transgene expression in combination with enhanced transgene capacity will further substantially improve AAV based vector technology

Human Cytomegalovirus (HCMV)-Specific CD4+ T Cells Are Polyfunctional and Can Respond to HCMV-Infected Dendritic Cells In Vitro.

Science.gov (United States)

Jackson, Sarah E; Sedikides, George X; Mason, Gavin M; Okecha, Georgina; Wills, Mark R

2017-03-15

Human cytomegalovirus (HCMV) infection and periodic reactivation are generally well controlled by the HCMV-specific T cell response in healthy people. While the CD8 + T cell response to HCMV has been extensively studied, the HCMV-specific CD4 + T cell effector response is not as well understood, especially in the context of direct interactions with HCMV-infected cells. We screened the gamma interferon (IFN-γ) and interleukin-10 (IL-10) responses to 6 HCMV peptide pools (pp65, pp71, IE1, IE2, gB, and US3, selected because they were the peptides most frequently responded to in our previous studies) in 84 donors aged 23 to 74 years. The HCMV-specific CD4 + T cell response to pp65, IE1, IE2, and gB was predominantly Th1 biased, with neither the loss nor the accumulation of these responses occurring with increasing age. A larger proportion of donors produced an IL-10 response to pp71 and US3, but the IFN-γ response was still dominant. CD4 + T cells specific to the HCMV proteins studied were predominantly effector memory cells and produced both cytotoxic (CD107a expression) and cytokine (macrophage inflammatory protein 1β secretion) effector responses. Importantly, when we measured the CD4 + T cell response to cytomegalovirus (CMV)-infected dendritic cells in vitro , we observed that the CD4 + T cells produced a range of cytotoxic and secretory effector functions, despite the presence of CMV-encoded immune evasion molecules. CD4 + T cell responses to HCMV-infected dendritic cells were sufficient to control the dissemination of virus in an in vitro assay. Together, the results show that HCMV-specific CD4 + T cell responses, even those from elderly individuals, are highly functional and are directly antiviral. IMPORTANCE Human cytomegalovirus (HCMV) infection is carried for a lifetime and in healthy people is kept under control by the immune system. HCMV has evolved many mechanisms to evade the immune response, possibly explaining why the virus is never eliminated

Prenatal Diagnosis of Congenital Cytomegalovirus Infection

Science.gov (United States)

Lazzarotto, T.; Guerra, B.; Spezzacatena, P.; Varani, S.; Gabrielli, L.; Pradelli, P.; Rumpianesi, F.; Banzi, C.; Bovicelli, L.; Landini, M. P.

1998-01-01

We report here the results of a study on the prenatal diagnosis of congenital cytomegalovirus (CMV) infection. The study was carried out by both PCR and virus isolation from amniotic fluid (AF) for 82 pregnant women at risk of transmitting CMV for the detection of (i) seroconversion to CMV immunoglobulin G (IgG) positivity during the first trimester of pregnancy, (ii) symptomatic CMV infection in the mother during the first trimester of pregnancy or intrauterine growth retardation detected by ultrasound or abnormal ultrasonographic findings suggestive of fetal infections, and (iii) seropositivity for CMV-specific IgM. For 50 women, fetal blood (FB) was also obtained and tests for antigenemia and PCR were performed. The results indicate that AF is better than FB for the prenatal diagnosis of CMV infection. PCR with AF has a sensitivity (SNS) of 100%, a specificity (SPE) of 83.3%, a positive predictive value (PPV) of 40%, and a negative predictive value (NPV) of 100%; rapid virus isolation with the same material has an SNS of 50%, an SPE of 100%, a PPV of 100%, and an NPV of 94.7%. Fewer than 10% of the women positive for IgM by enzyme immunoassay (EIA) had a congenitally infected fetus or newborn infant. When EIA IgM positivity was confirmed by Western blotting (WB) and the WB profile was considered, the percent transmission detected among women with an “at-risk” profile was higher than that observed among IgM-positive women and was the same as that among women who seroconverted during the first trimester of pregnancy (transmission rates of 29 and 25%, respectively). PMID:9817869

Public health and laboratory considerations regarding newborn screening for congenital cytomegalovirus.

Science.gov (United States)

Dollard, Sheila C; Schleiss, Mark R; Grosse, Scott D

2010-10-01

Congenital cytomegalovirus (CMV) infection is the most common infection in newborns worldwide and causes hearing loss and other neurological disability in 15-20% of infected infants. Only about half of the hearing loss resulting from congenital CMV infection is currently detected by universal newborn hearing screening because of late-onset hearing loss. Thus, much of the hearing loss and the majority of other CMV-associated disabilities remain undetected for years after birth and are never connected to CMV infection. Congenital CMV may be appropriate to include in national newborn screening (NBS) programs because it is more common than other disorders tested for by NBS programs and is a major cause of disability. Significant obstacles to the implementation of screening for congenital CMV include the lack of a standardized, high-throughput screening test and a protocol for follow-up of CMV-infected children. Nonetheless, screening newborns for congenital CMV infection merits further consideration.

Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

Science.gov (United States)

Pérez, J L

1997-09-01

Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

Computed tomography for diagnosis of intestinal cytomegalovirus infection in AIDS

International Nuclear Information System (INIS)

Engelbrecht, V.; Schonlau, R.; Moedder, U.

1994-01-01

To check the value of computed tomography (CT) in the diagnosis of cytomegalovirus (CMV) infection of the intestine, CT findings in ten patients with coloscopically proven CMV infection were reviewed. All patients were chronically ill men with AIDS. In nine of the ten cases CT scans of the small intestine and/or colon disclosed abnormalities. The predominant alteration (9/9) was a symmetric wall thickening in the bowel segments involved (10-30 mm). The location and extent showed good agreement with the inflammatory areas seen on coloscopy. The cecum and terminal ileum were the regions most frequently affected. In seven of the nine patients with CT abnormalities CT revealed pericolonic inflammation, particularly around the cecum. Lymph nodes were increased but not enlarged. Comparison of the findings in intestinal CMV infection with those in other AIDS-related diseases suggests that CT may be to limit the differential diagnosis. Abdominal CT serves as suitable primary imaging modality for the initial evaluation of patients with AIDS and abdominal symptoms of unknow etiology. (orig.)

Expression of biologically active murine interleukin-18 in Lactococcus lactis.

Science.gov (United States)

Feizollahzadeh, Sadegh; Khanahmad, Hossein; Rahimmanesh, Ilnaz; Ganjalikhani-Hakemi, Mazdak; Andalib, Alireza; Sanei, Mohammad Hossein; Rezaei, Abbas

2016-11-01

The food-grade bacterium Lactococcus lactis is increasingly used for heterologous protein expression in therapeutic and industrial applications. The ability of L. lactis to secrete biologically active cytokines may be used for the generation of therapeutic cytokines. Interleukin (IL)-18 enhances the immune response, especially on mucosal surfaces, emphasizing its therapeutic potential. However, it is produced as an inactive precursor and has to be enzymatically cleaved for maturation. We genetically manipulated L. lactis to secrete murine IL-18. The mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149 plasmid and the construct was used to transform L. lactis NZ3900. The transformants were selected on Elliker agar and confirmed by restriction enzyme digestion and sequencing. The expression and secretion of IL-18 protein was verified by SDS-PAGE, western blotting and ELISA. The biological activity of recombinant IL-18 was determined by its ability to induce interferon (IFN)-γ production in L. lactis co-cultured with murine splenic T cells. The amounts of IL-18 in bacterial lysates and supernatants were 3-4 μg mL -1 and 0.6-0.7 ng mL -1 , respectively. The successfully generated L. lactis strain that expressed biologically active murine IL-18 can be used to evaluate the possible therapeutic effects of IL-18 on mucosal surfaces. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Murine typhus in two travelers returning from Bali, Indonesia: an underdiagnosed disease.

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Takeshita, Nozomi; Imoto, Kazuya; Ando, Shuji; Yanagisawa, Kunio; Ohji, Goh; Kato, Yasuyuki; Sakata, Akiko; Hosokawa, Naoto; Kishimoto, Toshio

2010-01-01

Two Japanese travelers from Bali were diagnosed with murine typhus in Japan during the same period. Although one had only mild illness, the other experienced liver and kidney dysfunction. Murine typhus may be missed not only in endemic areas around the world, but also in travelers, especially those returning from marine resorts in these areas. © 2010 International Society of Travel Medicine.

Neurological Disorders in a Murine Model of Chronic Renal Failure

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Jean-Marc Chillon

2014-01-01

Full Text Available Cardiovascular disease is highly prevalent in patients with chronic renal failure (CRF. However, data on the impact of CRF on the cerebral circulatory system are scarce—despite the fact that stroke is the third most common cause of cardiovascular death in people with CRF. In the present study, we examined the impact of CRF on behavior (anxiety, recognition and ischemic stroke severity in a well-defined murine model of CRF. We did not observe any significant increases between CRF mice and non-CRF mice in terms of anxiety. In contrast, CRF mice showed lower levels of anxiety in some tests. Recognition was not impaired (vs. controls after 6 weeks of CRF but was impaired after 10 weeks of CRF. Chronic renal failure enhances the severity of ischemic stroke, as evaluated by the infarct volume size in CRF mice after 34 weeks of CRF. Furthermore, neurological test results in non-CRF mice tended to improve in the days following ischemic stroke, whereas the results in CRF mice tended to worsen. In conclusion, we showed that a murine model of CRF is suitable for evaluating uremic toxicity and the associated neurological disorders. Our data confirm the role of uremic toxicity in the genesis of neurological abnormalities (other than anxiety.

Validation of the use of an artificial mitochondrial reporter DNA vector containing a Cytomegalovirus promoter for mitochondrial transgene expression.

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Yamada, Yuma; Ishikawa, Takuya; Harashima, Hideyoshi

2017-08-01

Mitochondria have their own gene expression system that is independent of the nuclear system, and control cellular functions in cooperation with the nucleus. While a number of useful technologies for achieving nuclear transgene expression have been reported, only a few have focused on mitochondria. In this study, we validated the utility of an artificial mitochondrial DNA vector with a virus promoter on mitochondrial transgene expression. We designed and constructed pCMV-mtLuc (CGG) that contains a CMV promotor derived from Cytomegalovirus and an artificial mitochondrial genome with a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system. Nluc luciferase activity measurements showed that the pCMV-mtLuc (CGG) efficiently produced the Nluc luciferase protein in human HeLa cells. Moreover, we optimized the mitochondrial transfection of pCMV-mtLuc (CGG) using a MITO-Porter system, a liposome-based carrier for mitochondrial delivery via membrane fusion. As a result, we found that transfection of pCMV-mtLuc (CGG) by MITO-Porter modified with the KALA peptide (cationic amphipathic cell-penetrating peptide) showed a high mitochondrial transgene expression. The developed mitochondrial transgene expression system represents a potentially useful tool for the fields of nanoscience and nanotechnology for controlling the intracellular microenvironment via the regulation of mitochondrial function and promises to open additional innovative research fields of study. Copyright © 2017 Elsevier Ltd. All rights reserved.

A real time chemotaxis assay unveils unique migratory profiles amongst different primary murine macrophages.

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Asif J Iqbal

Full Text Available Chemotaxis assays are an invaluable tool for studying the biological activity of inflammatory mediators such as CC chemokines, which have been implicated in a wide range of chronic inflammatory diseases. Conventional chemotaxis systems such as the modified Boyden chamber are limited in terms of the data captured given that the assays are analysed at a single time-point. We report the optimisation and validation of a label-free, real-time cell migration assay based on electrical cell impedance to measure chemotaxis of different primary murine macrophage populations in response to a range of CC chemokines and other chemoattractant signalling molecules. We clearly demonstrate key differences in the migratory behavior of different murine macrophage populations and show that this dynamic system measures true macrophage chemotaxis rather than chemokinesis or fugetaxis. We highlight an absolute requirement for Gαi signaling and actin cytoskeletal rearrangement as demonstrated by Pertussis toxin and cytochalasin D inhibition. We also studied the chemotaxis of CD14(+ human monocytes and demonstrate distinct chemotactic profiles amongst different monocyte donors to CCL2. This real-time chemotaxis assay will allow a detailed analysis of factors that regulate macrophage responses to chemoattractant cytokines and inflammatory mediators.

A Real Time Chemotaxis Assay Unveils Unique Migratory Profiles amongst Different Primary Murine Macrophages

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Iqbal, Asif J.; Regan-Komito, Daniel; Christou, Ivy; White, Gemma E.; McNeill, Eileen; Kenyon, Amy; Taylor, Lewis; Kapellos, Theodore S.; Fisher, Edward A.; Channon, Keith M.; Greaves, David R.

2013-01-01

Chemotaxis assays are an invaluable tool for studying the biological activity of inflammatory mediators such as CC chemokines, which have been implicated in a wide range of chronic inflammatory diseases. Conventional chemotaxis systems such as the modified Boyden chamber are limited in terms of the data captured given that the assays are analysed at a single time-point. We report the optimisation and validation of a label-free, real-time cell migration assay based on electrical cell impedance to measure chemotaxis of different primary murine macrophage populations in response to a range of CC chemokines and other chemoattractant signalling molecules. We clearly demonstrate key differences in the migratory behavior of different murine macrophage populations and show that this dynamic system measures true macrophage chemotaxis rather than chemokinesis or fugetaxis. We highlight an absolute requirement for Gαi signaling and actin cytoskeletal rearrangement as demonstrated by Pertussis toxin and cytochalasin D inhibition. We also studied the chemotaxis of CD14+ human monocytes and demonstrate distinct chemotactic profiles amongst different monocyte donors to CCL2. This real-time chemotaxis assay will allow a detailed analysis of factors that regulate macrophage responses to chemoattractant cytokines and inflammatory mediators. PMID:23516549

Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands.

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Stowell, Jennifer D; Forlin-Passoni, Daniela; Radford, Kay; Bate, Sheri L; Dollard, Sheila C; Bialek, Stephanie R; Cannon, Michael J; Schmid, D Scott

2014-01-01

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 10(5) infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands.

Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

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Mayumi Oakland

2013-01-01

Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

Direct quantification of human cytomegalovirus immediate-early and late mRNA levels in blood of lung transplant recipients by competitive nucleic acid sequence-based amplification

NARCIS (Netherlands)

Greijer, AE; Verschuuren, EAM; Harmsen, MC; Dekkers, CAJ; Adriaanse, HMA; The, TH; Middeldorp, JM

The dynamics of active human cytomegalovirus (HCMV) infection was monitored by competitive nucleic acid sequence-based amplification (NASBA) assays for quantification of IE1 (UL123) and pp67 (UL65) mRNA expression levels In the blood of patients after lung transplantation. RNA was isolated from 339

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

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Marcell Cserhalmi

2017-09-01

Full Text Available Factor H-related (FHR proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH. While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3, and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

Identification and characterization of a silencer regulatory element in the 3'-flanking region of the murine CD46 gene.

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Nomura, M; Tsujimura, A; Begum, N A; Matsumoto, M; Wabiko, H; Toyoshima, K; Seya, T

2000-01-01

The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3'-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8 kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein-silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46. PMID:11023821

Interleukin-6 promotes systemic lupus erythematosus progression with Treg suppression approach in a murine systemic lupus erythematosus model.

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Mao, Xiaoli; Wu, Yunyun; Diao, Huitian; Hao, Jianlei; Tian, Gaofei; Jia, Zhenghu; Li, Zheng; Xiong, Sidong; Wu, Zhenzhou; Wang, Puyue; Zhao, Liqing; Yin, Zhinan

2014-11-01

Our aim is to reveal the role of interleukin 6 (IL-6) in the pathogenesis of systemic lupus erythematosus (SLE) in a murine model of SLE. Normal female C57BL/6 mice were immunized with syngeneic-activated lymphocyte-derived DNA (ALD-DNA) to induce SLE. Non-immunized mice were used as control. SLE-associated markers, including anti-double-stranded DNA (anti-dsDNA) Abs, urine protein, and kidney histopathology, were assayed to ensure the induction of the disease. Compared with control mice, ALD-DNA immunized mice exhibited high levels of anti-dsDNA Abs, IL-6 expression in vivo and in vitro. We also found that IL-6 knockout (IL-6KO) mice were resistant to ALD-DNA-induced SLE. The activation of CD4(+) T cells in immunized IL-6KO mice was lower than in immunized wild-type (Wt) mice. Intracellular cytokine staining showed that Foxp3 expression in immunized IL-6KO mice was higher than in immunized Wt mice, which might be associated with the disease severity. We further discovered that ALD-DNA-stimulated dendritic cells supernatants could result in higher IL-6 and TNF-α expression and could suppress Foxp3 expression. In addition, blocking IL-6 could up-regulate Foxp3 expression. Therefore, our findings show that IL-6 promotes the progression of SLE via suppressing Treg differentiation.

DMPD: Toll-like receptor 9 in murine lupus: more friend than foe! [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18241699 Toll-like receptor 9 in murine lupus: more friend than foe! Yu P, Musette ...us: more friend than foe! PubmedID 18241699 Title Toll-like receptor 9 in murine lupus...P, Peng SL. Immunobiology. 2008;213(2):151-7. Epub 2007 Sep 21. (.png) (.svg) (.html) (.csml) Show Toll-like receptor 9 in murine lup

Cytomegalovirus and immunotherapy: opportunistic pathogen, novel target for cancer and a promising vaccine vector.

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Quinn, Michael; Erkes, Dan A; Snyder, Christopher M

2016-02-01

Cytomegalovirus (CMV) is a β-herpesvirus that infects most people in the world and is almost always asymptomatic in the healthy host. However, CMV persists for life, requiring continuous immune surveillance to prevent disease and thus, CMV is a frequent complication in immune compromised patients. Many groups have been exploring the potential for adoptive T-cell therapies to control CMV reactivation as well as the progression of solid tumors harboring CMV. In addition, CMV itself is being explored as a vaccine vector for eliciting potent T-cell responses. This review will discuss key features of the basic biology of CMV-specific T cells as well as highlighting unanswered questions and ongoing work in the development of T-cell-based immunotherapies to target CMV.

Congenital cytomegalovirus infection: treatment, sequelae and follow-up.

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Lombardi, Giuseppina; Garofoli, Francesca; Stronati, Mauro

2010-10-01

Cytomegalovirus (CMV) is the most common cause of congenital infection affecting about 1% of all the live births worldwide. Its prevalence in the developed world seems to be slightly lower, ranging between 0.6 and 0.7%. Symptoms can be detected at birth in 10-15% of the congenitally infected of which 50-90% will develop sequelae, the most frequent being sensorineural hearing loss (SNHL), visual defect, psychomotor impairment, mental retardation, cerebral palsy and seizures. Eighty-five to 90% of the infected newborns are asymptomatic but 10-15% of them are equally at risk for sensorineural sequelae, like 20-30% of all the infected children. Therefore it is important a time prolonged and closer follow-up of infected children that we propose should be until 6 years of age. This should lead to an early intervention, better management and eventually even control the long-term sequelae. Infants born with symptomatic congenital infection have a worse prognosis than those with no evidence of clinical disease, and ganciclovir (GCV) intravenous 6 mg/kg every 12 h for 6 weeks is the most used therapy for symptomatic newborns. Valganciclovir (V-GCV) syrup is a pro-drug of GCV and presents high oral bioavailability. To date, it is possible to administer this drug at home, and the tolerability profile may allow for wider indications and longer treatments.

Vertically transmitted cytomegalovirus infection in newborn preterm infants.

Science.gov (United States)

Balcells, Carla; Botet, Francesc; Gayete, Sònia; Marcos, M Ángeles; Dorronsoro, Izaskun; de Alba, Concepción; Figueras-Aloy, Josep

2016-07-01

To determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV. During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols. Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05-0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk. The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.

Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells

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Dalle-Donne Isabella

2008-10-01

Full Text Available Abstract Background Recent studies demonstrate that recombinant adeno-associated virus (rAAV-based antigen loading of dendritic cells (DCs generates in vitro, significant and rapid cytotoxic T-lymphocyte (CTL responses against viral antigens. Methods We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1, expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then investigated the efficiency of the CTLs in killing IE1 targeted cells. Results A significant MHC Class I-restricted, anti-IE1-specific CTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC after one, in vitro, stimulation. Conclusion In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.

Biomechanical Properties of Murine Meniscus Surface via AFM-based Nanoindentation

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Li, Qing; Doyran, Basak; Gamer, Laura W.; Lu, X. Lucas; Qin, Ling; Ortiz, Christine; Grodzinsky, Alan J.; Rosen, Vicki; Han, Lin

2015-01-01

This study aimed to quantify the biomechanical properties of murine meniscus surface. Atomic force microscopy (AFM)-based nanoindentation was performed on the central region, proximal side of menisci from 6- to 24-week old male C57BL/6 mice using microspherical tips (Rtip ≈ 5 μm) in PBS. A unique, linear correlation between indentation depth, D, and response force, F, was found on menisci from all age groups. This non-Hertzian behavior is likely due to the dominance of tensile resistance by the collagen fibril bundles on meniscus surface that are mostly aligned along the circumferential direction observed on 12-week old menisci. The indentation resistance was calculated as both the effective stiffness, Sind = dF/dD, and the effective modulus, Eind, via the isotropic Hertz model. Values of Sind and Eind were found to depend on indentation rate, suggesting the existence of poro-viscoelasticity. These values do not significantly vary with anatomical sites, lateral versus medial compartments, or mouse age. In addition, Eind of meniscus surface (e.g., 6.1 ± 0.8 MPa for 12 weeks of age, mean ± SEM, n = 13) was found to be significantly higher than those of meniscus surfaces in other species, and of murine articular cartilage surface (1.4 ± 0.1 MPa, n = 6). In summary, these results provided the first direct mechanical knowledge of murine knee meniscus tissues. We expect this understanding to serve as a mechanics-based benchmark for further probing the developmental biology and osteoarthritis symptoms of meniscus in various murine models. PMID:25817332

The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting

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Hornig, Julia; Choi, K. Yeon; McGregor, Alistair, E-mail: mcgregor@medicine.tamhsc.edu

2017-04-15

Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234–474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection.

The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting

Science.gov (United States)

Hornig, Julia; Choi, K. Yeon; McGregor, Alistair

2017-01-01

Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234–474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection. PMID:28189970

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

DEFF Research Database (Denmark)

Børglum, A D; Demontis, D; Grove, J

2014-01-01

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals...... born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases...... was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies....

[Virulence of Sporothrix globosa in murine models].

Science.gov (United States)

Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Congenital Cytomegalovirus among Children with Cerebral Palsy.

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Smithers-Sheedy, Hayley; Raynes-Greenow, Camille; Badawi, Nadia; Fernandez, Marian A; Kesson, Alison; McIntyre, Sarah; Leung, Kin-Chuen; Jones, Cheryl A

2017-02-01

To determine the proportion of children with cerebral palsy (CP) and cytomegalovirus (CMV) DNA detected retrospectively in their newborn screening cards (NBSC), to compare the proportion of children with CMV DNA in their NBSC across spastic subtypes of CP, and to compare the sex and other characteristics of children with CP and CMV detected on their NSBC with those in whom CMV DNA was not detected. Retrospective observational study. Data were extracted from patient records on children with CP (birth years 1996-2014) from 2 Australian state CP registers and state-wide paediatric rehabilitation services with consent. NBSCs were retrospectively analyzed for CMV DNA by nested polymerase chain reaction (PCR) using primers against gB. Positive samples were validated using real time PCR for CMV UL83. Of 401 children recruited, 323 (80.5%) had an available NBSC. Of these, 31 (9.6%; 95% CI, 6.8-13.3) tested positive for CMV DNA by nested PCR for CMV gB, of whom 28 (8.7%; 95% CI, 6.1-12.2) also had CMV DNA detected by real-time PCR for CMV UL83. Detection of CMV DNA was significantly associated with epilepsy, but not with clinical or epidemiologic characteristics, including sex and pattern of spasticity. CMV viremia in the newborn period, indicating congenital CMV infection, is highly prevalent among children with CP. Further research is needed to investigate the mechanisms and contribution of congenital CMV to the causal pathways to CP. Copyright © 2016 Elsevier Inc. All rights reserved.

Attitudes toward newborn screening for cytomegalovirus infection.

Science.gov (United States)

Din, Erica S; Brown, Cedric J; Grosse, Scott D; Wang, Chengbin; Bialek, Stephanie R; Ross, Danielle S; Cannon, Michael J

2011-12-01

Newborns are not routinely screened for cytomegalovirus (CMV), the leading infectious cause of developmental disability. Congenital CMV satisfies a number of criteria for inclusion in newborn screening, and screening potentially offers benefits. Screening could also introduce harms such as anxiety and unnecessary costs for the families of the substantial proportion of CMV-infected children who never develop CMV-related disabilities. Our objective was to assess attitudes toward newborn screening for CMV. We analyzed responses to 5 statements about CMV and newborn screening from 3922 participants in the 2009 HealthStyles survey, a national mail survey designed to include a group similar to the US population with respect to gender, age, race/ethnicity, income, and household size. Two-step cluster analysis was performed to identify clusters of parental attitudes. The majority of respondents strongly or somewhat agreed that they would want to have their newborn tested for CMV even if it was not performed routinely (84%), they had to pay $20 (87%), or CMV-related problems never developed (84%). Nearly half (47%) of them "would worry that the CMV test would lead to unneeded doctor visits and expenses," and 32% "think CMV problems are too rare to worry about." Three clusters of parent respondents were identified on the basis of their attitudes toward CMV screening: "strongly in favor" (31%), "moderately in favor" (49%), and "weakly opposed" (20%). Among most parents, costs, worry, and anxiety associated with newborn screening for CMV would be acceptable. Although attitudes were generally favorable, a minority of the parents were weakly opposed to newborn screening for CMV.

Enhanced detection and study of murine norovirus-1 using a more efficient microglial cell line

Directory of Open Access Journals (Sweden)

Lu Yuanan

2009-11-01

Full Text Available Abstract Background Human Noroviruses are the predominant cause of non-bacterial gastroenteritis worldwide. To facilitate prevention and control, a norovirus isolated from mice can provide a model to understand human noroviruses. To establish optimal viral infectivity conditions for murine noroviruses, several cell lines of hematopoietic lineage, including murine BV-2, RAW 264.7, and TIB, as well as human CHME-5, were tested comparatively for their sensitivity to murine norovirus-1. Results Except for CHME-5, all three murine-derived cell lines were susceptible to MNV infection. Viral infection of these cells was confirmed by RT-PCR. Using both viral plaque and replication assays, BV-2 and RAW 264.7 cells were determined to have comparable sensitivities to MNV-1 infection. Comparisons of cell growth characteristics, general laboratory handling and potential in-field applications suggest the use of BV-2 to be more advantageous. Conclusion Results obtained from these studies demonstrate that an immortalized microglial cell line can support MNV-1 replication and provides a more efficient method to detect and study murine noroviruses, facilitating future investigations using MNV-1 as a model to study, detect, and control Human Norovirus.

Dose-effect relationship of apoptosis induced by fission-neutron in murine thymocytes

International Nuclear Information System (INIS)

Yuan Bin; Li Liang; Xue Wencheng; Sun Jianmin; Wang Baoqin

2000-01-01

Objective: To investigate the effectiveness of high LET fission-neutron to induce apoptosis in murine thymocytes and to compare it with that of low LET 60 Co γ-ray. Methods: Apoptosis induction was studied qualitatively by light and transmission electron microscopy and DNA gel electrophoresis,also quantitatively by flow cytometry(FCM) and diphenylamine (DPA)methods. Results: DNA ladders of murine thymocytes were detectable, the typical apoptosis of thymocytes could be observed morphologically by means of light and electron microscopy at 6 h after fission-neutron irradiation with doses ranging from 0.5 to 5.0 Gy, meanwhile the percentages of apoptosis increased with increasing doses. After exposure to γ-rays with doses ranging from 1.0 to 30 Gy, the experimental results were similar to those from neutron radiation. The incidence of apoptosis peaked at about 20 Gy, the percentages did not increase further when doses increased. Conclusion: Apoptosis of murine thymocytes can be induced when mice are exposed to either fission-neutron (0.5-5.0 Gy) or to γ-ray (1-30 Gy). Although the relationship between apoptosis and radiation doses is similar, the percentage of apoptosis induced by neutron irradiation is higher than that induced by γ-irradiation. The RBE values of fission-neutron for inducing apoptosis murine thymocytes are 2.09 (by FCM method) and 2.37 (by DPA method), respectively. These results also suggest that fission-neutron-induced murine immune tissue is more severe than that induced by γ-rays at several hours post-irradiation and this might be the basis for heavy damage to immune tissues induced by fission-neutron-irradiation in later period

Possible association between congenital cytomegalovirus infection and autistic disorder.

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Yamashita, Yushiro; Fujimoto, Chizu; Nakajima, Eisuke; Isagai, Takeo; Matsuishi, Toyojiro

2003-08-01

We encountered seven children with symptomatic congenital cytomegalovirus (CMV) infection from 1988 to 1995, of whom two (28.6%) developed typical autistic disorder. Case 1: A boy born at 38 weeks' gestation with a birth weight of 3164 g showed generalized petechiae, hepatosplenomegaly, and positive serum CMV-specific IgM antibodies. He was profoundly deaf, mentally retarded, and exhibited a lack of eye contact, stereotyped repetitive play, and hyperactivity. Case 2: A boy delivered at 39 weeks gestation with a birthweight of 2912 g showed non-progressive dilatation of the lateral ventricles observed postnatally. CMV-specific IgM antibodies were positive and CMV-DNA in the urine was confirmed by PCR. The boy was mentally retarded but not deaf. He showed no interest in people and delayed speech development. Subependymal cysts were detected by cranial ultrasound after birth in both patients. This is the first report describing subependymal cysts and the later development of AD. Cranial magnetic resonance imaging revealed an abnormal intensity area in the periventricular white matter suggestive of disturbed myelination; however, no migration disorders were found in our patients. These findings suggest that the timing of injury to the developing brain by CMV may be in the third trimester in some patients with autistic disorder.

Azithromycin prophylaxis and treatment of murine toxoplasmosis.

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Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M

2005-03-01

To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.

Late-onset cytomegalovirus infection complicated by Guillain-Barre syndrome in a kidney transplant recipient: case report and review of the literature.

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Shaban, E; Gohh, R; Knoll, B M

2016-04-01

Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature.

Enhanced capacity of DNA repair in human cytomegalovirus-infected cells

International Nuclear Information System (INIS)

Nishiyama, Y.; Rapp, F.

1981-01-01

Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate. Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone. A similar enhancement by HCMV was observed in human embryonic fibroblasts, but not in xeroderma pigmentosum (XP12BE) cells. It was also found that HCMV infection enhanced hydroxyurea-resistant DNA synthesis induced by UV light or methylmethanesulfonate. Alkaline sucrose gradient sedimentation analysis revealed an enhanced rate of synthesis of all size classes of DNA in UV-irradiated HCMV-infected Vero cells. However, HCMV infection did not induce repairable lesions in cellular DNA and did not significantly inhibit host cell DNA synthesis, unlike UV or methylmethanesulfonate. These results indicate that HCMV enhanced DNA repair capacity in the host cells without producing detectable lesions in cellular DNA and without inhibiting DNA synthesis. This repair appeared to be error proof for UV-damaged herpes simplex virus DNA when tested with herpes simplex virus thymidine kinase-negative mutants

Intrinsic Contribution of Perforin to NK-Cell Homeostasis during Mouse Cytomegalovirus Infection

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Maja eArapovic

2016-04-01

Full Text Available In addition to their role as effector cells in virus control, natural killer (NK cells have an immunoregulatory function in shaping the antiviral T-cell response. This function is further pronounced in perforin-deficient mice that show the enhanced NK-cell proliferation and cytokine secretion upon mouse cytomegalovirus (MCMV infection. Here we confirmed that stronger activation and maturation of NK cells in perforin-deficient mice correlates with higher MCMV load. To further characterize the immunoregulatory potential of perforin, we compared the response of NK cells that express or do not express perforin using bone-marrow chimeras. Our results demonstrated that the enhanced proliferation and maturation of NK cells in MCMV-infected bone-marrow chimeras is an intrinsic property of perforin-deficient NK cells. Thus, in addition to confirming that NK-cell proliferation is virus load dependent, our data extend this notion demonstrating that perforin plays an intrinsic role as a feedback mechanism in regulation of NK-cell proliferation during viral infections.

Chimeric anti-tenascin antibody 81C6: Increased tumor localization compared with its murine parent

International Nuclear Information System (INIS)

Zalutsky, Michael R.; Archer, Gary E.; Garg, Pradeep K.; Batra, Surinder K.; Bigner, Darell D.

1996-01-01

When labeled using the Iodogen method, a chimeric antibody composed of the human IgG 2 constant region and the variable regions of murine anti-tenascin 81C6 exhibited superior uptake in human glioma xenografts compared with its murine parent. In the current study, three paired-label experiments were performed in athymic mice with subcutaneous D-54 MG human glioma xenografts to evaluate further the properties of radioiodinated chimeric 81C6. These studies demonstrated that (a) the enhanced tumor uptake of chimeric 81C6 is specific; (b) when labeling was performed using N-succinimidyl 3-iodobenzoate, chimeric 81C6 again showed preferential accumulation in tumor compared with murine 81C6; and (c) the tumor uptake advantage observed previously with murine 81C6 for N-succinimidyl 3-iodobenzoate compared with Iodogen labeling did not occur with chimeric 81C6

Generation of murine tumor cell lines deficient in MHC molecule surface expression using the CRISPR/Cas9 system.

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Krishna Das

Full Text Available In this study, the CRISPR/Cas9 technology was used to establish murine tumor cell lines, devoid of MHC I or MHC II surface expression, respectively. The melanoma cell line B16F10 and the murine breast cancer cell line EO-771, the latter stably expressing the tumor antigen NY-BR-1 (EO-NY, were transfected with an expression plasmid encoding a β2m-specific single guide (sgRNA and Cas9. The resulting MHC I negative cells were sorted by flow cytometry to obtain single cell clones, and loss of susceptibility of peptide pulsed MHC I negative clones to peptide-specific CTL recognition was determined by IFNγ ELISpot assay. The β2m knockout (KO clones did not give rise to tumors in syngeneic mice (C57BL/6N, unless NK cells were depleted, suggesting that outgrowth of the β2m KO cell lines was controlled by NK cells. Using sgRNAs targeting the β-chain encoding locus of the IAb molecule we also generated several B16F10 MHC II KO clones. Peptide loaded B16F10 MHC II KO cells were insusceptible to recognition by OT-II cells and tumor growth was unaltered compared to parental B16F10 cells. Thus, in our hands the CRISPR/Cas9 system has proven to be an efficient straight forward strategy for the generation of MHC knockout cell lines. Such cell lines could serve as parental cells for co-transfection of compatible HLA alleles together with human tumor antigens of interest, thereby facilitating the generation of HLA matched transplantable tumor models, e.g. in HLAtg mouse strains of the newer generation, lacking cell surface expression of endogenous H2 molecules. In addition, our tumor cell lines established might offer a useful tool to investigate tumor reactive T cell responses that function independently from MHC molecule surface expression by the tumor.

A Focused Salivary Gland Infection with attenuated MCMV: An Animal Model with Prevention of Pathology Associated with Systemic MCMV Infection1, 2

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Pilgrim, Mark J.; Kasman, Laura; Grewal, Jasvir; Bruorton, Mary E.; Werner, Phil; London, Lucille; London, Steven D.

2010-01-01

While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inoculation. This study tested the hypothesis that MCMV morbidity and pathology could be reduced by injecting the virus directly the submandibular salivary gland (intraglandular (i.g.)), using either in vivo derived MCMV or the less virulent, tissue culture-derived MCMV (tcMCMV). Peak salivary gland viral titers were completely unaffected by infection route (i.p vs. i.g.) after inoculation with either MCMV or tcMCMV. However, i.g. tcMCMV inoculation reduced viremia in all systemic tissues tested compared to i.p. inoculation. Further, systemic organ pathology observed in the liver and spleen after i.p. inoculation with either MCMV or tcMCMV was completely eliminated by i.g. inoculation with tcMCMV. Cellular infiltrates in the salivary glands, after i.p. or i.g. inoculation were composed of both B and T cells, indicating the potential for a local immune response to occur in the salivary gland. These results demonstrate that a focused MCMV infection of the salivary gland without systemic organ pathology is possible using i.g. delivery of tcMCMV. PMID:17320076

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection

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Martha M. C. Elwenspoek

2017-10-01

Full Text Available Early life adversity (ELA increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59 or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18. No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57 in ELA. In addition, senescent T cells (CD57+ in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

Poly-thymidine oligonucleotides mediate activation of murine glial cells primarily through TLR7, not TLR8.

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Min Du

Full Text Available The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated by alternate ligands, which include vaccinia virus DNA, phosphothioate oligodeoxynucleotides (ODNs or the combination of phosphothioate poly-thymidine oligonucleotides (pT-ODNs with TLR7/8 agonists. In the current study, we analyzed the ability of pT-ODNs to induce activation of murine glial cells in the presence or absence of TLR7/8 agonists. We found that TLR7/8 agonists induced the expression of glial cell activation markers and induced the production of multiple proinflammatory cytokines and chemokines in mixed glial cultures. In contrast, pT-ODNs alone induced only low level expression of two cytokines, CCL2 and CXCL10. The combination of pT-ODNs along with TLR7/8 agonists induced a synergistic response with substantially higher levels of proinflammatory cytokines and chemokines compared to CL075. This enhancement was not due to cellular uptake of the agonist, indicating that the pT-ODN enhancement of cytokine responses was due to effects on an intracellular process. Interestingly, this response was also not due to synergistic stimulation of both TLR7 and TLR8, as the loss of TLR7 abolished the activation of glial cells and cytokine production. Thus, pT-ODNs act in synergy with TLR7/8 agonists to induce strong TLR7-dependent cytokine production in glial cells, suggesting that the combination of pT-ODNs with TLR7 agonists may be a useful mechanism to induce pronounced glial activation in the CNS.

Long-term results of oral valganciclovir for treatment of anterior segment inflammation secondary to cytomegalovirus infection

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Wong VW

2012-04-01

Full Text Available Victoria WY Wong, Carmen KM Chan, Dexter YL Leung, Timothy YY LaiDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Hong Kong, People's Republic of ChinaBackground: The purpose of this study was to assess the efficacy of oral valganciclovir in the treatment of anterior segment inflammation caused by cytomegalovirus (CMV infection.Methods: Consecutive patients with anterior segment inflammation due to CMV causing anterior uveitis or corneal endotheliitis treated with oral valganciclovir were reviewed. Diagnosis of CMV infection was confirmed by polymerase chain reaction of the aqueous aspirate prior to commencement of oral valganciclovir. All patients were treated with an oral loading dose of 900 mg valganciclovir twice daily for at least 2 weeks, followed by an additional 450 mg valganciclovir twice-daily maintenance therapy. Changes in visual acuity, intraocular pressure (IOP, use of antiglaucomatous eye drops, and recurrence were analyzed.Results: Thirteen eyes of 11 patients were followed for a mean of 17.2 months. Two patients had bilateral corneal endotheliitis. All eyes had absence of anterior segment inflammation within 3 weeks after treatment. Following treatment, the mean logMAR visual acuity improved significantly from 0.58 at baseline to 0.37 at the last follow-up (P = 0.048. The mean IOP and number of antiglaucomatous eye drops also decreased significantly (P = 0.021 and P = 0.004, respectively. Five (38.5% eyes had recurrence of anterior uveitis after valganciclovir was stopped and required retreatment with oral valganciclovir.Conclusion: Oral valganciclovir appeared to be effective in controlling CMV anterior uveitis, resulting in visual improvement and IOP reduction following control of inflammation. However, despite the initial clinical response in all cases, recurrence after cessation of oral valganciclovir could occur.Keywords: cytomegalovirus infection, inflammation

Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics.

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Fujii, Tomoyuki; Oka, Akira; Morioka, Ichiro; Moriuchi, Hiroyuki; Koyano, Shin; Yamada, Hideto; Saito, Shigeru; Sameshima, Hiroshi; Nagamatsu, Takeshi; Tsuchida, Shinya; Inoue, Naoki

2017-10-01

To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences. Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction-based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening. We used these 127 specimens, as well as 12 from cCMV cases identified in a previous study and 41 from healthy newborns, to compare the performance of 2 commercial assays and 1 in-house assay. The risk-based screening allowed the identification of cCMV cases at least 10-fold more efficiently than our previous universal screening, although there appears to be a limit to the identification of asymptomatically infected newborns. Although CMV-specific IgM during pregnancy was found frequently in mothers of cCMV newborns, CMV-IgM alone is not an effective diagnostic marker. The urine-filter-based assay and the 3 diagnostic assays yielded identical results. Although risk-based and universal newborn screening strategies for cCMV infection each have their respective advantages and disadvantages, urine-filter-based assay followed by confirmatory in vitro diagnostics assays is able to identify cCMV cases efficiently.

Stable integration of recombinant adeno-associated virus vector genomes after transduction of murine hematopoietic stem cells.

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Han, Zongchao; Zhong, Li; Maina, Njeri; Hu, Zhongbo; Li, Xiaomiao; Chouthai, Nitin S; Bischof, Daniela; Weigel-Van Aken, Kirsten A; Slayton, William B; Yoder, Mervin C; Srivastava, Arun

2008-03-01

We previously reported that among single-stranded adeno-associated virus (ssAAV) vectors, serotypes 1 through 5, ssAAV1 is the most efficient in transducing murine hematopoietic stem cells (HSCs), but viral second-strand DNA synthesis remains a rate-limiting step. Subsequently, using double-stranded, self-complementary AAV (scAAV) vectors, serotypes 7 through 10, we observed that scAAV7 vectors also transduce murine HSCs efficiently. In the present study, we used scAAV1 and scAAV7 shuttle vectors to transduce HSCs in a murine bone marrow serial transplant model in vivo, which allowed examination of the AAV proviral integration pattern in the mouse genome, as well as recovery and nucleotide sequence analyses of AAV-HSC DNA junction fragments. The proviral genomes were stably integrated, and integration sites were localized to different mouse chromosomes. None of the integration sites was found to be in a transcribed gene, or near a cellular oncogene. None of the animals, monitored for up to 1 year, exhibited pathological abnormalities. Thus, AAV proviral integration-induced risk of oncogenesis was not found in our study, which provides functional confirmation of stable transduction of self-renewing multipotential HSCs by scAAV vectors as well as promise for the use of these vectors in the potential treatment of disorders of the hematopoietic system.

Reversal of Liver Fibrosis in Chronic Murine Schistosomiasis ...

African Journals Online (AJOL)

NO Al-Harbi, SA Bahashwan, MS Aboonq, MA Ramadan, AA Bahashwan. Abstract. Purpose: To evaluate the safety, pharmacological effect and mechanism of action of an antifibrotic compound, safironil (SAF)/praziquantel (PZQ) combination on reversal of liver fibrogenesis in chronic murine Schistosomiasis mansoni.

A novel murine model for evaluating bovine papillomavirus prophylactics/therapeutics for equine sarcoid-like tumours.

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Bogaert, Lies; Woodham, Andrew W; Da Silva, Diane M; Martens, Ann; Meyer, Evelyne; Kast, W Martin

2015-09-01

Equine sarcoids are highly recurrent bovine papillomavirus (BPV)-induced fibroblastic neoplasms that are the most common skin tumours in horses. In order to facilitate the study of potential equine sarcoid prophylactics or therapeutics, which can be a slow and costly process in equines, a murine model for BPV-1 protein-expressing equine sarcoid-like tumours was developed in mice through stable transfection of BPV-1 E5 and E6 in a murine fibroblast tumour cell line (K-BALB). Like equine sarcoids, these murine tumour cells (BPV-KB) were of fibroblast origin, were tumorigenic and expressed BPV-1 proteins. As an initial investigation of the preclinical potential of this tumour model for equine sarcoids prophylactics, mice were immunized with BPV-1 E5E6 Venezuelan equine encephalitis virus replicon particles, prior to BPV-KB challenge, which resulted in an increased tumour-free period compared with controls, indicating that the BPV-KB murine model may be a valuable preclinical alternative to equine clinical trials.

Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system.

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Ivanova, Anna; Wuerfel, Jens; Zhang, Juan; Hoffmann, Olaf; Ballmaier, Matthias; Dame, Christof

2010-07-28

Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI. Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain. Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

Cost-benefit analysis of targeted hearing directed early testing for congenital cytomegalovirus infection.

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Bergevin, Anna; Zick, Cathleen D; McVicar, Stephanie Browning; Park, Albert H

2015-12-01

In this study, we estimate an ex ante cost-benefit analysis of a Utah law directed at improving early cytomegalovirus (CMV) detection. We use a differential cost of treatment analysis for publicly insured CMV-infected infants detected by a statewide hearing-directed CMV screening program. Utah government administrative data and multi-hospital accounting data are used to estimate and compare costs and benefits for the Utah infant population. If antiviral treatment succeeds in mitigating hearing loss for one infant per year, the public savings will offset the public costs incurred by screening and treatment. If antiviral treatment is not successful, the program represents a net cost, but may still have non-monetary benefits such as accelerated achievement of diagnostic milestones. The CMV education and treatment program costs are modest and show potential for significant cost savings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses.

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Dantoft, Widad; Martínez-Vicente, Pablo; Jafali, James; Pérez-Martínez, Lara; Martin, Kim; Kotzamanis, Konstantinos; Craigon, Marie; Auer, Manfred; Young, Neil T; Walsh, Paul; Marchant, Arnaud; Angulo, Ana; Forster, Thorsten; Ghazal, Peter

2017-01-01

Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV) is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1) and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1) roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity differences. These

Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses

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Widad Dantoft

2017-09-01

Full Text Available Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1 and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1 roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity

Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor

International Nuclear Information System (INIS)

Mochizuki, D.Y.; Eisenman, J.R.; Conlon, P.J.; Park, L.S.; Urdal, D.L.

1986-01-01

The expression in yeast of a cDNA clone encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has made possible the purification of large quantities of this recombinant protein. Rabbits immunized with pure recombinant GM-CSF generated antibodies that were shown to be specific for both recombinant GM-CSF and GM-CSF isolated from natural sources. Other lymphokines, including IL 1β, IL 2, IL 3, and recombinant human GM-CSF did not react with the antiserum. The antiserum together with recombinant GM-CSF that had been radiolabeled with 125 I to high specific activity, formed the foundation for a rapid, sensitive, and quantitative radioimmunoassay specific for murine GM-CSF. Furthermore, the antiserum was found to inhibit the biologic activities of GM-CSF as measured in both a bone marrow proliferation assay and a colony assay, and thus should prove to be a useful reagent for dissecting the complex growth factor activities involved in murine hematopoiesis

Protective effects of astaxanthin from Paracoccus carotinifaciens on murine gastric ulcer models.

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Murata, Kenta; Oyagi, Atsushi; Takahira, Dai; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Ishibashi, Takashi; Hara, Hideaki

2012-08-01

The purpose of this study was to investigate the effect of astaxanthin extracted from Paracoccus carotinifaciens on gastric mucosal damage in murine gastric ulcer models. Mice were pretreated with astaxanthin for 1 h before ulcer induction. Gastric ulcers were induced in mice by oral administration of hydrochloride (HCl)/ethanol or acidified aspirin. The effect of astaxanthin on lipid peroxidation in murine stomach homogenates was also evaluated by measuring the level of thiobarbituric acid reactive substance (TBARS). The free radical scavenging activities of astaxanthin were also measured by electron spin resonance (ESR) measurements. Astaxanthin significantly decreased the extent of HCl/ethanol- and acidified aspirin-induced gastric ulcers. Astaxanthin also decreased the level of TBARS. The ESR measurement showed that astaxanthin had radical scavenging activities against the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide anion radical. These results suggest that astaxanthin has antioxidant properties and exerts a protective effect against ulcer formation in murine models. Copyright © 2011 John Wiley & Sons, Ltd.

Single Amino Acid Insertion in Loop 4 Confers Amphotropic Murine Leukemia Virus Receptor Function upon Murine Pit1

DEFF Research Database (Denmark)

Lundorf, Mikkel D.; Pedersen, Finn Skou; O'Hara, Bryan

1998-01-01

Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch...

Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

Science.gov (United States)

Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O; Burzio, Verónica A

2016-09-06

We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

Preparation of Murine Submandibular Salivary Gland for Upright Intravital Microscopy.

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Ficht, Xenia; Thelen, Flavian; Stolp, Bettina; Stein, Jens V

2018-05-07

The submandibular salivary gland (SMG) is one of the three major salivary glands, and is of interest for many different fields of biological research, including cell biology, oncology, dentistry, and immunology. The SMG is an exocrine gland comprised of secretory epithelial cells, myofibroblasts, endothelial cells, nerves, and extracellular matrix. Dynamic cellular processes in the rat and mouse SMG have previously been imaged, mostly using inverted multi-photon microscope systems. Here, we describe a straightforward protocol for the surgical preparation and stabilization of the murine SMG in anesthetized mice for in vivo imaging with upright multi-photon microscope systems. We present representative intravital image sets of endogenous and adoptively transferred fluorescent cells, including the labeling of blood vessels or salivary ducts and second harmonic generation to visualize fibrillar collagen. In sum, our protocol allows for surgical preparation of mouse salivary glands in upright microscopy systems, which are commonly used for intravital imaging in the field of immunology.

Activation of PPAR{gamma} by Human Cytomegalovirus for de novo Replication Impairs Migration and Invasiveness of Cytotrophoblast from Early Placenta

DEFF Research Database (Denmark)

Rauwel, Benjamin; Mariamé, Bernard; Martin, Hélène

2010-01-01

, as assessed by using well-established in vitro models of invasive trophoblast i.e. primary cultures of EVCT isolated from first trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation, placentation...... and chromatin immunoprecipitation assays. Due to the key role of PPARgamma in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARgamma human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness...

Kinetics of IgG antibody to cytomegalovirus (CMV) after birth and seroprevalence of anti-CMV IgG in Chinese children

OpenAIRE

Chen, Jie; Hu, Lingqing; Wu, Meiling; Zhong, Tianying; Zhou, Yi-Hua; Hu, Yali

2012-01-01

Abstract Background Prevalence of cytomegalovirus (CMV) infection is 90–100% in developing countries; however, the kinetics of anti-CMV IgG in infants remains elusive. Methods Sera from 112 mother-newborn pairs and longitudinal samples from 41 infants up to 2-year old were tested for anti-CMV IgG and IgM. Additionally, samples from 837 healthy children were included. Results Of 112 mothers, 108 (96.4%) were anti-CMV IgG positive; their 108 newborns were also seropositive. In a 2-year follow-u...

Effect of in vitro and in vivo UV irradiation on the production of ETAF activity by human and murine keratinocytes

International Nuclear Information System (INIS)

Ansel, J.C.; Luger, T.A.; Green, I.

1983-01-01

Cultured epidermal cells and keratinocytes produce a potent hormone-like factor called epidermal cell-derived thymocyte-activating factor (ETAF). ETAF appears to be similar if not identical to a monocyte-derived lymphokine, known as interleukin 1 (IL-1). These two cytokines are able to amplify a diverse number of proliferative and inflammatory processes. Several recent investigations have suggested that UV-induced immunosuppression may be due in part to the inhibition of IL-1/ETAF production by monocytes and keratinocytes, respectively. We therefore decided to directly study the effects of various doses of in vitro and in vivo UV radiation (UVR) on the production of ETAF by normal murine epidermal cells and a murine (Pam 212) and a human (SCC) keratinocyte cell line. Our results surprisingly demonstrated an increase in both the extracellular and the intracellular ETAF activity of the murine epidermal, Pam 212, and SCC after sublethal amounts of in vitro UVR. Likewise, increased ETAF activity of murine epidermal cells was detected after sublethal doses of in vivo UVR. The UV-induced ETAF activity was cycloheximide-sensitive, suggesting that de novo synthesis of ETAF rather than cell membrane leakage was responsible for the increased ETAF activity. The fact that UV irradiation can increase ETAF activity by keratinocytes could have important local and systemic consequences for the host and may provide an efficient, contaminant-free method for generating ETAF activity for further biochemical and immunologic studies

Lipofection of early passages of cell cultures derived from murine adenocarcinomas: in vitro and ex vivo testing of the thymidine kinase/ganciclovir system.

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Karara, Armando L; Bumaschny, Viviana F; Fiszman, Gabriel L; Casais, Cecilia C; Glikin, Gerardo C; Finocchiaro, Liliana Me

2002-01-01

Early passages of cultured cells derived from four spontaneous Balb/c murine adenocarcinomas were used to explore the feasibility of a nonviral HSVtk-based suicide gene therapy system. After lipofection with pCMVtk, the transiently HSVtk expressing P07 (lung), M3, M05, and M38 (mammary gland) cells were, respectively, about 130-, 30-, 120-, and 170-fold more sensitive to ganciclovir (GCV) in vitro than their respective controls. Eighty percent of Balb/c mice subcutaneously inoculated with ex vivo pCMVtk-lipofected P07 cells, followed by intraperitoneal GCV injection for 7 days, displayed a complete inhibition of tumor growth for over 70 days. Control animals started to display tumors 13 days after inoculation. We present evidence showing that early passages of cultured tumor cells can efficiently express lipofected genes and that they are sensitive to the lipoplex-mediated HSVtk/GCV system.

Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission

OpenAIRE

Yoon, Jae-Ho; Lee, Seok; Kim, Hee-Je; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Yoo-Jin; Min, Chang-Ki; Cho, Seok-Goo; Min, Woo-Sung; Lee, Jong Wook

2016-01-01

Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice cons...

Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

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Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok

2000-01-01

The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21 WAF1/CIP1 . Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 WAF1/CIP1 . Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21 WAF1/CIP1

Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

2000-12-01

The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21{sup WAF1/CIP1}. Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 {sup WAF1/CIP1}. Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21{sup WAF1/CIP1}.

[Giant gastric ulcer by cytomegalovirus in infection VIH/SIDA].

Science.gov (United States)

Pérez-Pereyra, Julia; Morales, Domingo; Díaz, Ramiro; Yoza, Max; Frisancho, Oscar

2008-01-01

Cytomegalovirus infection is an important cause of morbidity in immunosupressed patients with Human Immunodeficiency Virus (HIV). In this paper we present a 43 years old man with renal failure under hemodialysis, several blood transfusions because of anemia and three months of disease characterized by epigastric pain, specially at nights, ameliorated with antacid drugs. Other symptoms were early satisfy, vomits and weigh loss (18Kg). At clinical exam, the patient was pallid, presented adenopathies at cervical and inguinal regions and had a pain at epigastric region in profound touch palpation. The most important exams were HB: 10mg/dl, CMV: 83.5, leukocytes 7000, lymphocytes: 1715, erythrocyte sedimentation rate 49mm/h, the venon test (-), and Giardia lamblia trophozoites in stools. The studies demonstrated the patient was seropositive for HIV and the tests for IgG CMV and IgG Herpes virus resulted seropositives too. At endoscopy the esophagus mucosa was covered by a white plaque which suggests candida infection. In the stomach, over the body gastric, we found a big and deep ulcerated lesion (45 x 41mm), with defined rims and white fund. Biopsy from the edges of the gastric ulcer had the characteristic CMV intranuclear and intracytoplasmic inclusions; we confirmed the diagnosis by immunohystochemistry. The patient receives ganciclovir an then HAART and is getting well.

Cytomegalovirus neutralization by hyperimmune and standard intravenous immunoglobulin preparations.

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Planitzer, Christina B; Saemann, Marcus D; Gajek, Hartwig; Farcet, Maria R; Kreil, Thomas R

2011-08-15

Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests. CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations. Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations. The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

Poly-N-acetylglucosamine production in Staphylococcus aureus is essential for virulence in murine models of systemic infection.

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Kropec, Andrea; Maira-Litran, Tomas; Jefferson, Kimberly K; Grout, Martha; Cramton, Sarah E; Götz, Friedrich; Goldmann, Donald A; Pier, Gerald B

2005-10-01

The contribution of the Staphylococcus aureus surface polysaccharide poly-N-acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin (ica) locus that encodes the biosynthetic enzymes for PNAG production in S. aureus strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the S. aureus inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect ica transcription, PNAG synthesis, and biofilm formation, we also evaluated S. aureus strains Mn8 and 10833 deleted for the sarA gene in the renal infection model. A decrease in PNAG production was seen in sarA mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of sarA-deleted strains in this model. S. aureus strains deleted for the ica genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on S. aureus resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by S. aureus appears to be a critical virulence factor as assessed in murine models of systemic infection.

Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism.

Science.gov (United States)

Ziegler, Kathryn M; Considine, Robert V; True, Eben; Swartz-Basile, Deborah A; Pitt, Henry A; Zyromski, Nicholas J

2016-04-01

Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p TGP-47 cells. These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Antigen-specific murine T cell clones produce soluble interleukin 2 receptor on stimulation with specific antigens

International Nuclear Information System (INIS)

Wagner, D.K.; York-Jolley, J.; Malek, T.R.; Berzofsky, J.A.; Nelson, D.L.

1986-01-01

In this study, monoclonal antibodies were used to the murine IL 2 receptor (IL 2R) termed 3C7 and 7D4, which bind to different epitopes on the murine IL 2R, to develop an ELISA to measure soluble murine IL 2R. Surprisingly, stimulated murine spleen cells not only expressed cell-associated IL 2R, but also produced a considerable level of cellfree IL 2R in the culture supernatant fluid. To assess the fine specificity of this response, myoglobin-immune murine T cell clones were stimulated with appropriate or inappropriate antigen and syngeneic or allogeneic presenting cells. Proliferation, measured by [ 3 H] thymidine incorporation, and levels of soluble IL 2R were determined at day 4. The production of soluble IL2R displayed the same epitope fine specificity, genetic restriction, and antigen dose-response as the proliferative response. Indeed, in some cases there was sharper discrimination of epitope specificity and genetic restriction with the soluble IL 2R levels. There was also reproducible clone-to-clone variation in the amount of soluble receptor produced in response to antigen among 12 T cell clones and lines tested. In time course experiments, proliferation was greatest at day 3, whereas soluble IL 2R levels continued to rise in subsequent days. To the authors' knowledge, this is the first demonstration of release of secretion of soluble IL 2R by murine T cells, and the first demonstration of the fine specificity and genetic restriction of the induction of soluble IL 2R by specific antigen

Modulation of phenotypic and functional maturation of murine dendritic cells (DCs) by purified Achyranthes bidentata polysaccharide (ABP).

Science.gov (United States)

Zou, Yaxuan; Meng, Jingjuan; Chen, Wenna; Liu, Jingling; Li, Xuan; Li, Weiwei; Lu, Changlong; Shan, Fengping

2011-08-01

There are a large number of interactions at molecular and cellular levels between the plant polysaccharides and immune system. Plant polysaccharides present an interesting effects as immunomodulators, particularly in the induction of the cells both in innate and adaptive immune systems. Activation of DCs could improve antitumoral responses usually diminished in cancer patients, and natural adjuvants provide a possibility of inducing this activation. ABP is a purified polysaccharide isolated from Achyranthes bidentata, a traditional Chinese medicine (TCM). The aim of this study is to investigate modulation of phenotypic and functional maturation of murine DCs by ABP. Both phenotypic and functional activities were assessed with use of conventional scanning electronic microscopy (SEM) for the morphology of the DC, transmitted electron microscopy (TEM) for intracellular lysosomes inside the DC, cellular immunohistochemistry for phagocytosis by the DCs, flow cytometry (FCM) for the changes in key surface molecules, bio-assay for the activity of acidic phosphatases (ACP), and ELISA for the production of pro-inflammatory cytokine IL-12. In fact, we found that purified ABP induced phenotypic maturation revealed by increased expression of CD86, CD40, and MHC II. Functional experiments showed the down-regulation of ACP inside DCs (which occurs when phagocytosis of DCs is decreased, and antigen presentation increased with maturation). Finally, ABP increased the production of IL-12. These data reveal that ABP promotes effective activation of murine DCs. This adjuvant-like activity may have therapeutic applications in clinical settings where immune responses need boosting. It is therefore concluded that ABP can exert positive modulation to murine DCs. Copyright © 2011 Elsevier B.V. All rights reserved.

A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.

Directory of Open Access Journals (Sweden)

Ryan W Carroll

Full Text Available BACKGROUND: Cerebral malaria (CM is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA. Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field. The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

Apoptosis of infiltrating T cells in the central nervous system of mice infected with Theiler's murine encephalomyelitis virus

International Nuclear Information System (INIS)

Oleszak, Emilia L.; Hoffman, Brad E.; Chang, J. Robert; Zaczynska, Ewa; Gaughan, John; Katsetos, Christos D.; Platsoucas, Chris D.; Harvey, Nile

2003-01-01

Theiler murine encephalomyelitis virus (TMEV), DA strain, induces in susceptible strain of mice a biphasic disease consisting of early acute disease followed by late chronic demyelinating disease. Both phases of the disease are associated with inflammatory infiltrates of the central nervous system (CNS). Late chronic demyelinating disease induced by TMEV serves as an excellent model to study human demyelinating disease, multiple sclerosis. During early acute disease, the virus is partially cleared from the CNS by CD3 + T cells. These T cells express Fas, FasL, negligible levels of Bcl-2 proteins and undergo activation-induced cell death as determined by TUNEL assay leading to resolution of the inflammatory response. In contrast, during late chronic demyelinating disease, and despite dense perivascular and leptomeningeal infiltrates, only very few cells undergo apoptosis. Mononuclear cells infiltrating the CNS express Bcl-2. It appears that the lack of apoptosis of T cells during late chronic demyelinating disease leads to the accumulation of these cells in the CNS. These cells may play a role in the pathogenesis of the demyelinating disease

The Role of the MHV Receptor and Related Glycoproteins in Murine Hepatitis Virus Infection of Murine Cell Lines

Science.gov (United States)

1995-04-13

vaccinia virus-T7 RNA polymerase s y stem for e xpression of target genes . Mol . Cell . BioI . 7 : 2538-2544 . Gagneten , S ., Gout , 0 ., Dubois-Dalcq...glycoprotein. These results showed f or the first time that two murine CEA- related genes can be co-expressed in some cell lines from inbred mice...49 Southern Hybridization ................ . ............ 50 Subcloning of PCR Products and Gene Cloning ........ 51 Growth

Generation of thermostable Moloney murine leukemia virus reverse transcriptase variants using site saturation mutagenesis library and cell-free protein expression system.

Science.gov (United States)

Katano, Yuta; Li, Tongyang; Baba, Misato; Nakamura, Miyo; Ito, Masaaki; Kojima, Kenji; Takita, Teisuke; Yasukawa, Kiyoshi

2017-12-01

We attempted to increase the thermostability of Moloney murine leukemia virus (MMLV) reverse transcriptase (RT). The eight-site saturation mutagenesis libraries corresponding to Ala70-Arg469 in the whole MMLV RT (Thr24-Leu671), in each of which 1 out of 50 amino acid residues was replaced with other amino acid residue, were constructed. Seven-hundred and sixty eight MMLV RT clones were expressed using a cell-free protein expression system, and their thermostabilities were assessed by the temperature of thermal treatment at which they retained cDNA synthesis activity. One clone D200C was selected as the most thermostable variant. The highest temperature of thermal treatment at which D200C exhibited cDNA synthesis activity was 57ºC, which was higher than for WT (53ºC). Our results suggest that a combination of site saturation mutagenesis library and cell-free protein expression system might be useful for generation of thermostable MMLV RT in a short period of time for expression and selection.

Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model.

LENUS (Irish Health Repository)

Monk, Ian R

2010-01-01

Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells.

Seroepidemiology of cytomegalovirus infections in Croatia.

Science.gov (United States)

Vilibic-Cavlek, Tatjana; Kolaric, Branko; Beader, Natasa; Vrtar, Izabela; Tabain, Irena; Mlinaric-Galinovic, Gordana

2017-02-01

Cytomegalovirus (CMV) is endemic worldwide, with marked differences in the seroprevalence rates between countries. The aim of this study was to analyze the seroprevalence of CMV infections in Croatia. During a 3-year period (2013-2015) 2438 consecutive serum samples collected from Croatian residents were tested for the presence of CMV IgM and IgG antibodies using enzyme-linked immunoassay. The IgM/IgG positive samples were further tested for IgG avidity. The overall seroprevalence rates for CMV IgG and IgM antibodies were 74.4 % and 4.3 %, respectively. The IgG seroprevalence showed significant differences between population groups: children/adolescents 54.6 %, general adult population 77.2 %, hemodialysis patients 91.4 % (p < 0.001). Seropositivity of CMV was strongly age-dependent with prevalences ranging from 53.0 % in children less than 10 years old to 93.8 % in persons above 60 years (p < 0.001). There was no difference in the prevalence rate between women with normal pregnancy and women with poor obstetric history. Gender and place of residence were not associated with CMV seropositivity. Using IgG avidity, current/recent primary CMV infection was confirmed by a low/borderline avidity index (AI) in 46.7 % participants, while in 53.3 % a high AI indicated CMV reactivation or reinfection. Primary infections were detected mainly in children and adolescents (83.2 % and 70.5 %, respectively), while reactivation/reinfection was common in persons older than 40 (77.0-100 %). Reactivation/reinfection was most commonly detected in hemodialysis patients (92.3 %). Logistic regression showed that older age and being on hemodialysis were significant predictors of CMV seropositivity. Infections with CMV are widespread in the Croatian population. Older age and being on hemodialysis appear to be the main risk factors for CMV infection.

The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study

Directory of Open Access Journals (Sweden)

Pazoki Raha

2006-12-01

Full Text Available Abstract Background The metabolic syndrome together with insulin resistance and their consequences are basic factors in pathogenesis of atherosclerosis. Chronic infections with herpes simplex virus type 1 (HSV-1, cytomegalovirus (CMV, and Chlamydia pneumoniae are associated with the development of atherosclerosis and coronary heart disease. The infectious aspects of metabolic syndrome have not been investigated. Methods In a cross-sectional, population-based study, we used National Cholesterol Education Program (NCEP-Adult Treatment Panel (ATP-III criteria in 1791 subjects, aged 25 years and over, selected by cluster random sampling in three Iranian ports in the northern Persian Gulf. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, HSV-1, Helicobacter pylori (H. pylori and CMV using ELISA. Results In multiple logistic regression analysis, of the infectious agents, CMV [OR = 1.81 (1.05–3.10; p = 0.03], H. pylori [OR = 1.50 (1.12–2.00; p = 0.007] and Chlamydia pneumoniae [OR = 1.69 (1.27–2.25; p Conclusion The metabolic syndrome, which occurs very frequently in the general population, has a significant association with prior infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus type 1. Hypothesis about participation of infection in pathogenesis of metabolic syndrome should be investigated.

An Italian Prospective Experience on the Association Between Congenital Cytomegalovirus Infection and Autistic Spectrum Disorder.

Science.gov (United States)

Garofoli, Francesca; Lombardi, Giuseppina; Orcesi, Simona; Pisoni, Camilla; Mazzucchelli, Iolanda; Angelini, Micol; Balottin, Umberto; Stronati, Mauro

2017-05-01

The aim of this retrospective study, with prospective data collection, was to correlate congenital cytomegalovirus (CMV) infection with autism spectrum disorder (ASD) and to define its prevalence. Seventy proven congenitally-infected infants, born between 2007 and 2012, were referred to our centre for CMV diagnosis and follow-up, which consisted of a consolidated protocol allowing an early evaluation of autism. We considered four children 2-year old, two of whom, at the age of 3, were diagnosed with ASD demonstrating a 2-3 fold higher prevalence (2.86%), than that in general Italian population (0.66-1.36%).Our protocol enabled us to make the earliest diagnosis and highlight the role of the virus among other causes of autism, which may be a long term sequela of congenital CMV.

Sequential Expression of the Neuropeptides Substance P and Somatostatin in Granulomas Associated with Murine Cysticercosis

OpenAIRE

Robinson, Prema; White, A. Clinton; Lewis, Dorothy E.; Thornby, John; David, Elliott; Weinstock, Joel

2002-01-01

Neurocysticercosis, a parasitic infection of the human central nervous system caused by Taenia solium, is a leading cause of seizures. Seizures associated with neurocysticercosis are caused mainly by the host inflammatory responses to dying parasites in the brain parenchyma. We previously demonstrated sequential expression of Th1 cytokines in early-stage granulomas, followed by expression of Th2 cytokines in later-stage granulomas in murine cysticercosis. However, the mechanism leading to thi...

Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

Energy Technology Data Exchange (ETDEWEB)

Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

1990-05-01

The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

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Mark R. Schleiss

2013-01-01

Full Text Available Fetal and neonatal infections caused by human cytomegalovirus (CMV are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies.

Human embryonic stem cell lines model experimental human cytomegalovirus latency.

Science.gov (United States)

Penkert, Rhiannon R; Kalejta, Robert F

2013-05-28

Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

Science.gov (United States)

Schleiss, Mark R.

2013-01-01

Fetal and neonatal infections caused by human cytomegalovirus (CMV) are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies. PMID:24023565

Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

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Sonia M. Restrepo-Gualteros

2014-05-01

Full Text Available Cytomegalovirus (CMV is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years, using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%, hypoxemia (100%, diffuse adventitious breath sounds (100% and increased respiratory effort (93%. All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate or histology/immunohistochemistry in lung biopsy (100% detection rate. CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes.

Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

DEFF Research Database (Denmark)

Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel

2017-01-01

of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin...... A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher...... selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate...

Nuclear trafficking of the human cytomegalovirus pp71 (ppUL82) tegument protein

International Nuclear Information System (INIS)

Shen Weiping; Westgard, Elizabeth; Huang Liqun; Ward, Michael D.; Osborn, Jodi L.; Chau, Nha H.; Collins, Lindsay; Marcum, Benjamin; Koach, Margaret A.; Bibbs, Jennifer; Semmes, O. John; Kerry, Julie A.

2008-01-01

The human cytomegalovirus tegument protein pp71 localizes to the nucleus immediately upon infection, and functions to initiate viral gene expression. Analysis of a series of random insertion mutations revealed that sequences within the mid region (MR) of pp71 are important for localization to the nucleus. Fusion of MR sequences with eGFP revealed that amino acids 94 to 300 were sufficient to target proteins to the nucleus. Random substitution mutagenesis within this domain resulted in two double substitution mutants, pp71P203T/T223M and pp71T228M/L275Q, with a predominantly cytoplasmic localization. Disruption of nuclear targeting resulted in relocalization of the fusion proteins to a distinct perinuclear region. Using tandem mass spectrometry, we determined that threonine 223 can be phosphorylated. Mutation of this residue to a phosphomimetic amino acid resulted in abrogation of nuclear targeting. These results strongly suggest that the intracellular trafficking of pp71 is regulated by phosphorylation

A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

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Coleman, Stewart; Choi, K Yeon; Root, Matthew; McGregor, Alistair

2016-07-01

In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model.

Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

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Want MY

2017-03-01

Full Text Available Muzamil Y Want,1 Mohammad Islammudin,1 Garima Chouhan,1 Hani A Ozbak,2 Hassan A Hemeg,2 Asoke P Chattopadhyay,3 Farhat Afrin2 1Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India; 2Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia; 3Department of Chemistry, University of Kalyani, Kalyani, India Abstract: Visceral leishmaniasis (VL is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a

AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections.

Science.gov (United States)

Heddle, Nancy M; Boeckh, Michael; Grossman, Brenda; Jacobson, Jessica; Kleinman, Steven; Tobian, Aaron A R; Webert, Kathryn; Wong, Edward C C; Roback, John D

2016-06-01

Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components. © 2016 AABB.

BST2/Tetherin enhances entry of human cytomegalovirus.

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Kasinath Viswanathan

2011-11-01

Full Text Available Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV, indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV.

Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg.

Science.gov (United States)

van de Vrugt, Henri J; Koomen, Mireille; Berns, Mariska A D; de Vries, Yne; Rooimans, Martin A; van der Weel, Laura; Blom, Eric; de Groot, Jan; Schepers, Rik J; Stone, Stacie; Hoatlin, Maureen E; Cheng, Ngan Ching; Joenje, Hans; Arwert, Fré

2002-03-01

Fanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder. Six distinct FA disease genes have been identified, the products of which function in an integrated pathway that is thought to support a nuclear caretaker function. Comparison of FA gene characteristics in different species may help to unravel the molecular function of the FA pathway. We have cloned the murine homologue of the Fanconi anaemia complementation group G gene, FANCG/XRCC9. The murine Fancg protein shows an 83% similarity to the human protein sequence, and has a predicted molecular weight of 68.5 kDa. Expression of mouse Fancg in human FA-G lymphoblasts fully corrects their cross-linker hypersensitivity. At mRNA and protein levels we detected the co-expression of Fancg and Fanca in murine tissues. In addition, mouse Fancg and Fanca proteins co-purify by immunoprecipitation. Upon transfection into Fanca-deficient mouse embryonic fibroblasts EGFP-Fancg chimeric protein was detectable in the nucleus. We identified a murine cDNA, Fancg, which cross-complements the cellular defect of human FA-G cells and thus represents a true homologue of human FANCG. Spleen, thymus and testis showed the highest Fancg expression levels. Although Fancg and Fanca are able to form a complex, this interaction is not required for Fancg to accumulate in the nuclear compartment.

Non- invasive in vivo analysis of a murine aortic graft using high resolution ultrasound microimaging

International Nuclear Information System (INIS)

Rowinska, Zuzanna; Zander, Simone; Zernecke, Alma; Jacobs, Michael; Langer, Stephan; Weber, Christian; Merx, Marc W.; Koeppel, Thomas A.

2012-01-01

Introduction: As yet, murine aortic grafts have merely been monitored histopathologically. The aim of our study was to examine how these grafts can be monitored in vivo and non-invasively by using high-resolution ultrasound microimaging to evaluate function and morphology. A further aim was to prove if this in vivo monitoring can be correlated to immunohistological data that indicates graft integrity. Methods: Murine infrarenal aortic isografts were orthotopically transplanted into 14 female mice (C57BL/6-Background) whereas a group of sham-operated animals (n = 10) served as controls. To assess the graft morphology and hemodynamics, we examined the mice over a post-operative period of 8 weeks with a sophisticated ultrasound system (Vevo 770, Visual Sonics). Results: The non-invasive graft monitoring was feasible in all transplanted mice. We could demonstrate a regular post-transplant graft function and morphology, such as anterior/posterior wall displacement and wall thickness. Mild alterations of anterior wall motion dynamics could only be observed at the site of distal graft anastomosis (8 weeks after grafting (transplant vs. sham mice: 0.02 mm ± 0.01 vs. 0.03 mm ± 0.01, p < 0.05). However, the integrity of the entire graft wall could be confirmed by histopathological evaluation of the grafts. Conclusions: With regard to graft patency, function and morphology, high resolution ultrasound microimaging has proven to be a valuable tool for longitudinal, non-invasive, in vivo graft monitoring in this murine aortic transplantation model. Consequently, this experimental animal model provides an excellent basis for molecular and pharmacological studies using genetically engineered mice.

Cytomegalovirus seropositivity is associated with herpes zoster

Science.gov (United States)

Ogunjimi, Benson; Hens, Niel; Pebody, Richard; Jansens, Hilde; Seale, Holly; Quinlivan, Mark; Theeten, Heidi; Goossens, Herman; Breuer, Judy; Beutels, Philippe

2015-01-01

Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N = 223) in order to compare the results with those from UK population samples (N = 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 = 1741, N2 = 576), USA (N = 5572) and Australia (N = 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMV-seroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ. PMID:25905443

Murine alpha1-adrenoceptor subtypes. I. Radioligand binding studies

NARCIS (Netherlands)

Yang, M.; Reese, J.; Cotecchia, S.; Michel, M. C.

1998-01-01

Alpha1-adrenoceptors were identified in murine tissues by [3H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

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Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

[Ganciclovir therapy for congenital cytomegalovirus infection in newborn infants: a meta analysis].

Science.gov (United States)

Hu, Jin-Tao; Chen, Ping-Yang; Xie, Zong-De; Dang, Xi-Qiang; Wang, Tao; He, Xiao-Ri; Li, Wen; Bo, Tao

2010-01-01

To evaluate the efficacy and safety of ganciclovir therapy for congenital cytomegalovirus (CMV) infection in newborn infants. The randomized controlled trials (RCTs) and quasi-RCTs on ganciclovir therapy for congenital CMV were reviewed in the following electronic databases: PubMed (January 1988 to January 2009), EMbase (January 1988 to January 2009), the Cochrane library (Issue 3, 2003 and Issue 1, 2009), the Chinese Journals Full-text Database (January 1994 to January 2009), the Chinese Biological Medical Disc (January 1994 to January 2009) and the Chinese Medical Current Contents (January 1994 to January 2009). Quality assessment, data extraction, and meta analysis were performed. Ten papers were included. Meta analysis showed that the ganciclovir therapy increased the improvement rate (91.4% vs 34.0%; pCMV infection indexes to become negative in more patients (87.6% vs 15.3%; pCMV infection indexes becoming negative, and decrease incidence of hearing disturbance, with few side effects, in newborn infants with CMV infection. However the supporting evidence is not strong due to few trials and more high-quality research is needed.

Signaling pathways regulating murine pancreatic development

DEFF Research Database (Denmark)

Serup, Palle

2012-01-01

The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...... been identified and the specific roles have been investigated by genetic and cell biological methods. The present review presents an overview of the principal signaling pathways involved in regulating murine pancreatic growth, morphogenesis, and cell differentiation....

Comparison of enzyme-linked immunosorbent assay, radioimmunoassay, complement fixation, anticomplement immunofluorescence and passive haemaglutination techniques for detecting cytomegalovirus IgG antibody

Energy Technology Data Exchange (ETDEWEB)

Booth, J C; Hannington, G; Bakir, T M.F.; Stern, H; Kangro, H; Griffiths, P D; Heath, R B [Saint George' s Hospital Medical School, London (UK); Saint Bartholomew' s Hospital, London (UK))

1982-12-01

The radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques were found to be comparable in sensitivity and specificity for detecting cytomegalovirus IgG antibody, and 10 to 100 times more sensitive than complement-fixation (CF), anticomplement immunofluorescence (ACIF) and passive haemagglutination (PHA). In screening tests for antibody, the frequency of false-positive and -negative results was 0.6% for RIA and ELISA, 1.5% for CF, 1.6% for ACIF and 3.6% for PHA. PHA was the least satisfactory test, largely because of technical problems.

Epidemiology of cytomegalovirus infection in pregnant women living in the Greater Romagna Area, Italy

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Patrizia Billi

2015-12-01

Full Text Available Background. Aim of this study was to assess the incidence of Cytomegalovirus (CMV infection in pregnant women living in Romagna area, in North East Italy to implement the best management of this infection. Materials and Methods. In 2012, 23,727 serological tests for CMV IgG and IgM antibodies were performed in the Microbiology Unit, the Hub Laboratory of the Greater Romagna Area: 6931 were pregnant women. Results and Conclusions. 179 subjects were positive for CMV IgM antibodies: 82 were not pregnant; 97 were IgM positive during pregnancy or in the course of a pre-conception evaluation. The detected incidence of the CMV infection in pregnancy (calculated at 1.40% actually validates the literature data. This study’s findings clearly underline the usefulness of testing the CMV specific immune response in the pre-conception period or as early as possible during pregnancy.

Temporal Regulation of fim Genes in Uropathogenic Escherichia coli during Infection of the Murine Urinary Tract

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William R. Schwan

2017-01-01

Full Text Available Uropathogenic Escherichia coli (UPEC adhere to cells in the human urinary tract via type 1 pili that undergo phase variation where a 314-bp fimS DNA element flips between Phase-ON and Phase-OFF orientations through two site-specific recombinases, FimB and FimE. Three fim-lux operon transcriptional fusions were created and moved into the clinical UPEC isolate NU149 to determine their temporal regulation in UPEC growing in the urinary tract. Within murine urinary tracts, the UPEC strains demonstrated elevated transcription of fimA and fimB early in the infection, but lower transcription by the fifth day in murine kidneys. In contrast, fimE transcription was much lower than either fimA or fimB early, increased markedly at 24 h after inoculation, and then dropped five days after inoculation. Positioning of fimS was primarily in the Phase-ON position over the time span in UPEC infected bladders, whereas in UPEC infected murine kidneys the Phase-OFF orientation was favored by the fifth day after inoculation. Hemagglutination titers with guinea pig erythrocytes remained constant in UPEC growing in infected murine bladders but fell substantially in UPEC infected kidneys over time. Our results show temporal in vivo regulation of fim gene expression in different environmental niches when UPEC infects the murine urinary tract.

Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

DEFF Research Database (Denmark)

Steentoft, Catharina; Schjoldager, Katrine T; Cló, Emiliano

2010-01-01

antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity...... of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O......-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin...

IL-10 down-regulates the expression of survival associated gene hspX of Mycobacterium tuberculosis in murine macrophage

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Babban Jee

2017-07-01

Full Text Available Mycobacterium tuberculosis (MTB adopts a special survival strategy to overcome the killing mechanism(s of host immune system. Amongst the many known factors, small heat shock protein 16.3 (sHSP16.3 of MTB encoded by gene hspX has been reported to be critical for the survival of MTB. In the present study, the effect of recombinant murine interferon-gamma (rmIFN-γ and recombinant murine interleukin-10 (rmIL-10 on the expression of gene hspX of MTB in murine macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed that three increasing concentrations (5, 25 and 50 ng/ml of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50 ng/ml significantly down-regulated the hspX expression. This effect was not only dependent on the concentration of the stimulus but this was time-dependent as well. A contrasting pattern of hspX expression was observed against combinations of two different concentrations of rmIFN-γ and rmIL-10. The study results suggest that rIL-10 mediated down-regulation of hspX expression, in the presence of low concentration of rIFN-γ, could be used as an important strategy to decrease the dormancy of MTB in its host and thus making MTB susceptible to the standard anti-mycobacterial therapy used for treating tuberculosis. However, as these are only preliminary results in the murine cell line model, this hypothesis needs to be first validated in human cell lines and subsequently in animal models mimicking the latent infection using clinical isolates of MTB before considering the development of modified regimens for humans.

Human cytomegalovirus (HCMV) induces human endogenous retrovirus (HERV) transcription.

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Assinger, Alice; Yaiw, Koon-Chu; Göttesdorfer, Ingmar; Leib-Mösch, Christine; Söderberg-Nauclér, Cecilia

2013-11-12

Emerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription. Infection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 - 4 and HML-7 - 8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up-regulation of HERV activity was more pronounced in cells harbouring active HCMV infection, but was also induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes. Within this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types.

Immune Restoration Syndrome with disseminated Penicillium marneffei and Cytomegalovirus co-infections in an AIDS patient

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Wig Naveet

2007-10-01

Full Text Available Abstract Background Penicillium marneffei is a dimorphic fungus, endemic in South-east Asia. The fungus causes severe disease in immunocompromised patients such as AIDS. However, no case of immune restoration disease of Penicillium marneffei is reported in literature from a non-endemic area. Case Presentation We report the first case of Penicillium marneffei and Cytomegalovirus infection manifesting as a result of immune restoration one month after initiating HAART. This severely immunocompromised patient had presented with multiple lymphadenopathy, massive hepatosplenomegaly, visual impairment and mild icterus, but no skin lesions. Penicillium marneffei was isolated from lymph node fine-needle aspirates and blood cultures. Conclusion In order to diagnose such rare cases, the clinicians, histopathologists and microbiologists alike need to maintain a strong index of suspicion for making initial diagnosis as well as for suspecting immune reconstitution syndrome (IRS with Penicillium marneffei.

Reliable and inexpensive expression of large, tagged, exogenous proteins in murine bone marrow-derived macrophages using a second generation lentiviral system

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Matthew R. Miller

2015-08-01

Full Text Available Over the past two decades, researchers have struggled to efficiently express foreign DNA in primary macrophages, impeding research progress. The applications of lipofection, electroporation, microinjection, and viral-mediated transfer typically result in disruptions in macrophage differentiation and function, low expression levels of exogenous proteins, limited efficiency and high cell mortality. In this report, after extensive optimization, we present a method of expressing large tagged proteins at high efficiency, consistency, and low cost using lentiviral infection. This method utilizes laboratory-propagated second generation plasmids to produce efficient virus that can be stored for later use. The expression of proteins up to 150 kDa in size is achieved in 30–70% of cells while maintaining normal macrophage differentiation and morphology as determined by fluorescence microscopy and Western blot analysis. This manuscript delineates the reagents and methods used to produce lentivirus to express exogenous DNA in murine bone marrow-derived macrophages sufficient for single cell microscopy as well as functional assays requiring large numbers of murine bone marrow-derived macrophages.

Tenascin-C Prevents Articular Cartilage Degeneration in Murine Osteoarthritis Models.

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Matsui, Yuriyo; Hasegawa, Masahiro; Iino, Takahiro; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Sudo, Akihiro

2018-01-01

Objective The objective of this study was to determine whether intra-articular injections of tenascin-C (TNC) could prevent cartilage damage in murine models of osteoarthritis (OA). Design Fluorescently labeled TNC was injected into knee joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4 weeks postinjection. To investigate the effects of TNC on cartilage degeneration after surgery to knee joints, articular spaces were filled with 100 μg/mL (group I), 10 μg/mL (group II) of TNC solution, or control (group III). TNC solution of 10 μg/mL was additionally injected twice after 3 weeks (group IV) or weekly after 1 week, 2 weeks, and 3 weeks (group V). Joint tissues were histologically assessed using the Mankin score and the modified Chambers system at 2 to 8 weeks after surgery. Results Exogenous TNC was maintained in the cartilage and synovium for 1 week after administration. Histological scores in groups I and II were better than scores in group III at 4 and 6 weeks, but progressive cartilage damage was seen in all groups 8 weeks postoperatively. Sequential TNC injections (groups IV and V) showed significantly better Mankin score than single injection (group II) at 8 weeks. Conclusion TNC administered exogenously remained in the cartilage of knee joints for 1 week, and could decelerate articular cartilage degeneration in murine models of OA. We also showed that sequential administration of TNC was more effective than a single injection. TNC could be an important molecule for prevention of articular cartilage damage.

The role of adrenergic activation on murine luteal cell viability and progesterone production.

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Wang, Jing; Tang, Min; Jiang, Huaide; Wu, Bing; Cai, Wei; Hu, Chuan; Bao, Riqiang; Dong, Qiming; Xiao, Li; Li, Gang; Zhang, Chunping

2016-09-15

Sympathetic innervations exist in mammalian CL. The action of catecholaminergic system on luteal cells has been the focus of a variety of studies. Norepinephrine (NE) increased progesterone secretion of cattle luteal cells by activating β-adrenoceptors. In this study, murine luteal cells were treated with NE and isoprenaline (ISO). We found that NE increased the viability of murine luteal cells and ISO decreased the viability of luteal cells. Both NE and ISO promoted the progesterone production. Nonselective β-adrenergic antagonist, propranolol reversed the effect of ISO on cell viability but did not reverse the effect of NE on cell viability. Propranolol blocked the influence of NE and ISO on progesterone production. These results reveal that the increase of luteal cell viability induced by NE is not dependent on β-adrenergic activation. α-Adrenergic activation possibly contributes to it. Both NE and ISO increased progesterone production through activating β-adrenergic receptor. Further study showed that CyclinD2 is involved in the increase of luteal cell induced by NE. 3β-Hydroxysteroid dehydrogenase, LHR, steroidogenic acute regulatory protein (StAR), and PGF2α contribute to the progesterone production induced by NE and ISO. Copyright © 2016 Elsevier Inc. All rights reserved.

Adaptive changes in NAD+ metabolism in ultraviolet light-irradiated murine lymphoma cells

International Nuclear Information System (INIS)

Kleczkowska, H.E.; Szumiel, I.; Althaus, F.R.

1990-01-01

We have determined the ability of UV254nm-irradiated murine lymphoma cells to adapt their NAD+ metabolism to the increased NAD+ consumption for the poly ADP-ribosylation of chromatin proteins. Two murine lymphoma sublines with differential UV-sensitivity and poly(ADP-ribose) turnover were used as a model system. The first subline, designated LY-R is UV254nm-sensitive and tumorigenic in DBA/2 mice. The second subline, LY-S is UV254nm-resistant and nontumorigenic. Following treatment of these cells with 2 mM benzamide, an inhibitor of the NAD(+)-utilizing enzyme poly(ADP-ribose) polymerase, NAD+ levels slowly increased up to about 160% of control levels after 3 hours. When benzamide was added to these cultures 20 min after UV254nm irradiation, a dramatic transient increase of NAD+ levels was observed within 4 min in LY-R cells and more moderately in LY-S cells. At later times after UV254nm irradiation, the NAD+ levels increased in both sublines reaching up to 200% of the concentrations prior to benzamide treatment. These results demonstrate an adaptative response of NAD+ metabolism to UV254nm irradiation. In parallel, we observed a differential repartitioning of ADP-ribosyl residues between the NAD+ and poly(ADP-ribose) pools of LY-R and LY-S cells that correlates with the differential UV sensitivity of these cells

Sustained expression of human cytomegalovirus glycoprotein B (UL55) in the seeds of homozygous rice plants.

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Tackaberry, Eilleen S; Prior, Fiona A; Rowlandson, Karen; Tocchi, Monika; Mehic, Jelica; Porter, Suzanne; Walsh, Mike; Schleiss, Mark R; Ganz, Peter R; Sardana, Ravinder K; Altosaar, Illimar; Dudani, Anil K

2008-09-01

Production of recombinant subunit vaccines in transgenic plants may be a means of reducing vaccine costs while increasing availability and safety. A plant-derived product found safe and effective for oral administration would provide additional advantages when used as a vaccine. Outstanding issues with the technology include transgene stability through successive generations and consistent bioproduction. We previously reported expression of glycoprotein B (gB) of human cytomegalovirus in seeds of transgenic tobacco. Here the goal was to determine if gB could be similarly expressed in rice, and if so, to examine expression over several plant generations. Results show that immunoreactive gB was successfully expressed in transgenic rice seeds, with sustained expression over three generations. The gB contained several neutralizing epitopes and was stable over 27 months.

The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

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Michael Nevels

2009-11-01

Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

Effects of the murine skull in optoacoustic brain microscopy.

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Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

2016-01-01

Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative evaluation of three automated systems for DNA extraction in conjunction with three commercially available real-time PCR assays for quantitation of plasma Cytomegalovirus DNAemia in allogeneic stem cell transplant recipients.

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Bravo, Dayana; Clari, María Ángeles; Costa, Elisa; Muñoz-Cobo, Beatriz; Solano, Carlos; José Remigia, María; Navarro, David

2011-08-01

Limited data are available on the performance of different automated extraction platforms and commercially available quantitative real-time PCR (QRT-PCR) methods for the quantitation of cytomegalovirus (CMV) DNA in plasma. We compared the performance characteristics of the Abbott mSample preparation system DNA kit on the m24 SP instrument (Abbott), the High Pure viral nucleic acid kit on the COBAS AmpliPrep system (Roche), and the EZ1 Virus 2.0 kit on the BioRobot EZ1 extraction platform (Qiagen) coupled with the Abbott CMV PCR kit, the LightCycler CMV Quant kit (Roche), and the Q-CMV complete kit (Nanogen), for both plasma specimens from allogeneic stem cell transplant (Allo-SCT) recipients (n = 42) and the OptiQuant CMV DNA panel (AcroMetrix). The EZ1 system displayed the highest extraction efficiency over a wide range of CMV plasma DNA loads, followed by the m24 and the AmpliPrep methods. The Nanogen PCR assay yielded higher mean CMV plasma DNA values than the Abbott and the Roche PCR assays, regardless of the platform used for DNA extraction. Overall, the effects of the extraction method and the QRT-PCR used on CMV plasma DNA load measurements were less pronounced for specimens with high CMV DNA content (>10,000 copies/ml). The performance characteristics of the extraction methods and QRT-PCR assays evaluated herein for clinical samples were extensible at cell-based standards from AcroMetrix. In conclusion, different automated systems are not equally efficient for CMV DNA extraction from plasma specimens, and the plasma CMV DNA loads measured by commercially available QRT-PCRs can differ significantly. The above findings should be taken into consideration for the establishment of cutoff values for the initiation or cessation of preemptive antiviral therapies and for the interpretation of data from clinical studies in the Allo-SCT setting.

GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells.

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Guiyu Lou

Full Text Available GPBAR1/TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA receptor. BAs are known to induce the expression of inflammatory cytokines in the liver with unknown mechanism. Here we show that without other external stimuli, TGR5 activation alone induced the expression of interleukin 1β (IL-1β and tumor necrosis factor-α (TNF-α in murine macrophage cell line RAW264.7 or murine Kupffer cells. The TGR5-mediated increase of pro-inflammatory cytokine expression was suppressed by JNK inhibition. Moreover, the induced pro-inflammatory cytokine expression in mouse liver by 1% cholic acid (CA diet was blunted in JNK-/- mice. TGR5 activation by its ligands enhanced the phosphorylation levels, DNA-binding and trans-activities of c-Jun and ATF2 transcription factors. Finally, the induced pro-inflammatory cytokine expression in Kupffer cells by TGR5 activation correlated with the suppression of Cholesterol 7α-hydroxylase (Cyp7a1 expression in murine hepatocytes. These results suggest that TGR5 mediates the BA-induced pro-inflammatory cytokine production in murine Kupffer cells through JNK-dependent pathway. This novel role of TGR5 may correlate to the suppression of Cyp7a1 expression in hepatocytes and contribute to the delicate BA feedback regulation.

Differential activation of murine herpesvirus 68- and Kaposi's sarcoma-associated herpesvirus-encoded ORF74 G protein-coupled receptors by human and murine chemokines

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Verzijl, D.; Fitzsimons, C.P.; Van Dijk, M.; Stewart, J.P.; Timmerman, H.; Smit, M.J.; Leurs, R.

2004-01-01

Infection of mice with murine gammaherpesvirus 68 (MHV-68) is a well-characterized small animal model for the study of gammaherpesvirus infection. MHV-68 belongs to the same herpesvirus family as herpesvirus saimiri (HVS) of New World squirrel monkeys and human herpesvirus 8 (HHV-8) (also referred

Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission.

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Saldaña Garrido, J D; Martínez Rubio, M; Carrión Campo, R; Moya Moya, M A; Rico Sergado, L

2017-03-01

A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Expression of the Wilms' tumor gene WT1 in the murine urogenital system.

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Pelletier, J; Schalling, M; Buckler, A J; Rogers, A; Haber, D A; Housman, D

1991-08-01

The Wilms' tumor gene WT1 is a recessive oncogene that encodes a putative transcription factor implicated in nephrogenesis during kidney development. In this report we analyze expression of WT1 in the murine urogenital system. WT1 is expressed in non-germ-cell components of the testis and ovaries in both young and adult mice. In situ mRNA hybridization studies demonstrate that WT1 is expressed in the granulosa and epithelial cells of ovaries, the Sertoli cells of the testis, and in the uterine wall. In addition to the 3.1-kb WT1 transcript detected by Northern blotting of RNA from kidney, uterus, and gonads, there is an approximately 2.5-kb WT1-related mRNA species in testis. The levels of WT1 mRNA in the gonads are among the highest observed, surpassing amounts detected in the embryonic kidney. During development, these levels are differentially regulated, depending on the sexual differentiation of the gonad. Expression of WT1 mRNA in the female reproductive system does not fluctuate significantly from days 4 to 40 postpartum. In contrast, WT1 mRNA levels in the tesis increase steadily after birth, reaching their highest expression levels at day 8 postpartum and decreasing slightly as the animal matures. Expression of WT1 in the gonads is detectable as early as 12.5 days postcoitum (p.c.). As an initial step toward exploring the tissue-specific expression of WT1, DNA elements upstream of WT1 were cloned and sequenced. Three putative transcription initiation sites, utilized in testis, ovaries, and uterus, were mapped by S1 nuclease protection assays. The sequences surrounding these sites have a high G + C content, and typical upstream CCAAT and TATAA boxes are not present. These studies allowed us to identify the translation initiation site for WT1 protein synthesis. We have also used an epitope-tagging protocol to demonstrate that WT1 is a nuclear protein, consistent with its role as a transcription factor. Our results demonstrate regulation of WT1 expression

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

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Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

2006-01-01

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

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G Pomara

2009-06-01

Full Text Available We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry. Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Comparison of high-resolution computed tomography findings between Pseudomonas aeruginosa pneumonia and Cytomegalovirus pneumonia

International Nuclear Information System (INIS)

Omeri, Ahmad Khalid; Okada, Fumito; Takata, Shoko; Ono, Asami; Sato, Haruka; Mori, Hiromu; Nakayama, Tomoko; Ando, Yumiko; Hiramatsu, Kazufumi

2014-01-01

To compare pulmonary high-resolution CT (HRCT) findings in patients with Pseudomonas aeruginosa pneumonia to HRCT findings in patients with Cytomegalovirus (CMV) pneumonia. We studied 124 patients (77 men, 47 women; age range, 20-89 years; mean age, 65.4 years) with P. aeruginosa pneumonia and 44 patients (22 men, 22 women; age range, 36-86 years; mean age, 63.2 years) with CMV pneumonia. CT findings of consolidation (p < 0.005), bronchial wall thickening (p < 0.001), cavity (p < 0.05), and pleural effusion (p < 0.001) were significantly more frequent in patients with P. aeruginosa pneumonia than in those with CMV pneumonia. Centrilobular nodules, a crazy-paving appearance, and nodules were significantly more frequent in patients with CMV pneumonia than in those with P. aeruginosa pneumonia (all p < 0.001). Pulmonary HRCT findings, such as bronchial wall thickening, crazy-paving appearance, and nodules may be useful in distinguishing between P. aeruginosa pneumonia and CMV pneumonia. (orig.)

Comparison of high-resolution computed tomography findings between Pseudomonas aeruginosa pneumonia and Cytomegalovirus pneumonia

Energy Technology Data Exchange (ETDEWEB)

Omeri, Ahmad Khalid; Okada, Fumito; Takata, Shoko; Ono, Asami; Sato, Haruka; Mori, Hiromu [Oita University Faculty of Medicine, Department of Radiology, Yufu, Oita (Japan); Nakayama, Tomoko [Oita Red Cross Hospital, Department of Radiology, Oita (Japan); Ando, Yumiko [Oita Nishibeppu National Hospital, Department of Radiology, Oita (Japan); Hiramatsu, Kazufumi [Oita University Hospital, Hospital Infection Control Center, Oita (Japan)

2014-12-15

To compare pulmonary high-resolution CT (HRCT) findings in patients with Pseudomonas aeruginosa pneumonia to HRCT findings in patients with Cytomegalovirus (CMV) pneumonia. We studied 124 patients (77 men, 47 women; age range, 20-89 years; mean age, 65.4 years) with P. aeruginosa pneumonia and 44 patients (22 men, 22 women; age range, 36-86 years; mean age, 63.2 years) with CMV pneumonia. CT findings of consolidation (p < 0.005), bronchial wall thickening (p < 0.001), cavity (p < 0.05), and pleural effusion (p < 0.001) were significantly more frequent in patients with P. aeruginosa pneumonia than in those with CMV pneumonia. Centrilobular nodules, a crazy-paving appearance, and nodules were significantly more frequent in patients with CMV pneumonia than in those with P. aeruginosa pneumonia (all p < 0.001). Pulmonary HRCT findings, such as bronchial wall thickening, crazy-paving appearance, and nodules may be useful in distinguishing between P. aeruginosa pneumonia and CMV pneumonia. (orig.)

Absence of hypoxanthine:guanine phosphoribosyltransferase activity in murine Dunn osteosarcoma

International Nuclear Information System (INIS)

Abelson, H.T.; Gorka, C.

1983-01-01

The transplantable murine Dunn osteosarcoma has no detectable hypoxanthine:guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This was established from the tumors directly and from tissue culture cell lines derived from the tumor using a variety of assays: e.g., no [3H]hypoxanthine uptake into tumor or tissue culture cells, no conversion of [3H]hypoxanthine to [3H]IMP by cell extracts from tumors or tissue culture cells, no growth of tissue culture cells in hypoxanthine:aminopterin:thymidine medium, and normal growth of these cells in 10 microM 6-mercaptopurine. Ten human osteosarcomas have been assayed, and two have no apparent hypoxanthine:guanine phosphoribosyltransferase enzyme activity. After high-dose methotrexate treatment in vivo, murine tumors could be selectively killed and normal tissues could be spared by using a rescue regimen of hypoxanthine-thymidine-allopurinol

Local Delivery Is Critical for Monocyte Chemotactic Protein-1 Mediated Site-Specific Murine Aneurysm Healing.

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Hourani, Siham; Motwani, Kartik; Wajima, Daisuke; Fazal, Hanain; Jones, Chad H; Doré, Sylvain; Hosaka, Koji; Hoh, Brian L

2018-01-01

Local delivery of monocyte chemotactic protein-1 (MCP-1/CCL2) via our drug-eluting coil has been shown to promote intrasaccular aneurysm healing via an inflammatory pathway. In this study, we validate the importance of local MCP-1 in murine aneurysm healing. Whether systemic, rather than local, delivery of MCP-1 can direct site-specific aneurysm healing has significant translational implications. If systemic MCP-1 is effective, then MCP-1 could be administered as a pill rather than by endovascular procedure. Furthermore, we confirm that MCP-1 is the primary effector in our MCP-1 eluting coil-mediated murine aneurysm healing model. We compare aneurysm healing with repeated intraperitoneal MCP-1 versus vehicle injection, in animals with control poly(lactic-co-glycolic) acid (PLGA)-coated coils. We demonstrate elimination of the MCP-1-associated tissue-healing response by knockout of MCP-1 or CCR2 (MCP-1 receptor) and by selectively inhibiting MCP-1 or CCR2. Using immunofluorescent probing, we explore the cell populations found in healed aneurysm tissue following each intervention. Systemically administered MCP-1 with PLGA coil control does not produce comparable aneurysm healing, as seen with MCP-1 eluting coils. MCP-1-directed aneurysm healing is eliminated by selective inhibition of MCP-1 or CCR2 and in MCP-1-deficient or CCR2-deficient mice. No difference was detected in M2 macrophage and myofibroblast/smooth muscle cell staining with systemic MCP-1 versus vehicle in aneurysm wall, but a significant increase in these cell types was observed with MCP-1 eluting coil implant and attenuated by MCP-1/CCR2 blockade or deficiency. We show that systemic MCP-1 concurrent with PLGA-coated platinum coil implant is not sufficient to produce site-specific aneurysm healing. MCP-1 is a critical, not merely complementary, actor in the aneurysm healing pathway.

Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

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Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

2016-12-01

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

Peptide inhibition of human cytomegalovirus infection

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Morris Cindy A

2011-02-01

Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 �

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis.

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Tomoya Watanabe

Full Text Available The murine bleomycin (BLM-induced fibrosis model is the most widely used in systemic sclerosis (SSc studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.

Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

Directory of Open Access Journals (Sweden)

Hirotaka Yamamoto

2016-01-01

Full Text Available Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders.

Congenital cytomegalovirus infection: contribution and best timing of prenatal MR imaging

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Cannie, Mieke M. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Radiology, Brussels (Belgium); UZ Brussel, Vrije Universiteit Brussel, Department of Radiology, Brussel (Belgium); Devlieger, Roland; Catte, Luc de; Valk, Elise van der [University Hospitals Leuven, Department of Obstetrics and Gynecology, Leuven (Belgium); Leyder, Mina; Foulon, Walter [UZ Brussel, Vrije Universiteit Brussel, Department of Obstetrics, Brussel (Belgium); Claus, Filip [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Onze-Lieve-Vrouw Hospital, Department of Radiology, Aalst (Belgium); Leus, Astrid [UZ Brussel, Vrije Universiteit Brussel, Department of Radiology, Brussel (Belgium); Cossey, Veerle [University Hospitals Leuven, Neonatal Intensive Care Unit, Leuven (Belgium); Foulon, Ina [UZ Brussel, Vrije Universiteit Brussel, Department of Otolaryngology - Head and Neck Surgery, Brussel (Belgium); Cos, Teresa; Jani, Jacques C. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Obstetrics and Gynecology, Brussels (Belgium); Bernaert, Anja [Sint-Augustinus Hospital, Department of Radiology, Antwerp (Belgium); Oyen, Raymond [University Hospitals Leuven, Department of Radiology, Leuven (Belgium)

2016-10-15

To predict sensorineural hearing loss (SNHL) and neurological impairment in congenital cytomegalovirus (cCMV) infection using MR imaging and define the best timing in pregnancy for prenatal assessment. In 121 patients with confirmed cCMV infection, brain features at MR imaging were respectively graded from 1 to 5: normal; isolated frontal/parieto-occipital hyperintensity; temporal periventricular hyperintensity; temporal/occipital cysts and/or intraventricular septa; migration disorders. Grading was correlated with postnatal SNHL and neurological impairment using regression analysis. In 51 fetuses with MR examinations at 26.9 and 33.0 weeks, the predictive value of SNHL and neurological impairment was compared using ROC curves. Postnatal follow-up showed SNHL in 18 infants and neurological impairment in 10. MR grading was predictive of SNHL and of neurological impairment (P < 0.001). In grade 1 or 2, none had SNHL and 1/74 had neurological impairment. The areas under ROC curves for prediction of postnatal SNHL and of neurological impairment from first and second MR examination were comparable. Our data suggest that in cCMV infection, prediction of SNHL and neurological impairment is feasible by fetal MR imaging with a high negative predictive value and can equally be done at 27 or 33 weeks of gestation. (orig.)

Congenital cytomegalovirus infection: contribution and best timing of prenatal MR imaging

International Nuclear Information System (INIS)

Cannie, Mieke M.; Devlieger, Roland; Catte, Luc de; Valk, Elise van der; Leyder, Mina; Foulon, Walter; Claus, Filip; Leus, Astrid; Cossey, Veerle; Foulon, Ina; Cos, Teresa; Jani, Jacques C.; Bernaert, Anja; Oyen, Raymond

2016-01-01

To predict sensorineural hearing loss (SNHL) and neurological impairment in congenital cytomegalovirus (cCMV) infection using MR imaging and define the best timing in pregnancy for prenatal assessment. In 121 patients with confirmed cCMV infection, brain features at MR imaging were respectively graded from 1 to 5: normal; isolated frontal/parieto-occipital hyperintensity; temporal periventricular hyperintensity; temporal/occipital cysts and/or intraventricular septa; migration disorders. Grading was correlated with postnatal SNHL and neurological impairment using regression analysis. In 51 fetuses with MR examinations at 26.9 and 33.0 weeks, the predictive value of SNHL and neurological impairment was compared using ROC curves. Postnatal follow-up showed SNHL in 18 infants and neurological impairment in 10. MR grading was predictive of SNHL and of neurological impairment (P < 0.001). In grade 1 or 2, none had SNHL and 1/74 had neurological impairment. The areas under ROC curves for prediction of postnatal SNHL and of neurological impairment from first and second MR examination were comparable. Our data suggest that in cCMV infection, prediction of SNHL and neurological impairment is feasible by fetal MR imaging with a high negative predictive value and can equally be done at 27 or 33 weeks of gestation. (orig.)

Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing

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Dumortier, Jerome; Streblow, Daniel N.; Moses, Ashlee V.; Jacobs, Jon M.; Kreklywich, Craig N.; Camp, David G.; Smith, Richard D.; Orloff, Susan L.; Nelson, Jay

2008-07-01

Human cytomegalovirus (HCMV) is implicated in the acceleration of a number of vascular diseases including transplant vascular sclerosis (TVS), the lesion associated with chronic rejection (CR) of solid organ transplants. Although the virus persists in the allograft throughout the course of disease, few cells are directly infected by CMV. This observation is in contrast to the global effects that CMV has on the acceleration of TVS/CR, suggesting that CMV infection indirectly promotes the vascular disease process. Recent transcriptome analysis of CMV-infected heart allografts indicates that the virus induces cytokines and growth factors associated with angiogenesis (AG) and wound healing (WH), suggesting that CMV may accelerate TVS/CR through the induction and secretion of AG/WH factors from infected cells. We analyzed virus-free supernatants from HCMV-infected cells (HCMV secretomes) for growth factors, by mass spectrometry and immunoassays, and found that the HCMV secretome contains over 1,000 cellular proteins, many of which are involved in AG/WH. Importantly, functional assays demonstrated that CMV but not herpes simplex virus secretomes not only induce AG/WH but also promote neovessel stabilization and endothelial cell survival for 2 weeks. These findings suggest that CMV acceleration of TVS occurs through virus-induced growth factors and cytokines in the CMV secretome.

Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway.

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Magdalena Angelova

Full Text Available Human Cytomegalovirus (HCMV is a ubiquitous herpesvirus that currently infects a large percentage of the world population. Although usually asymptomatic in healthy individuals, HCMV infection during pregnancy may cause spontaneous abortions, premature delivery, or permanent neurological disabilities in infants infected in utero. During infection, the virus exerts control over a multitude of host signaling pathways. Wnt/β-catenin signaling, an essential pathway involved in cell cycle control, differentiation, embryonic development, placentation and metastasis, is frequently dysregulated by viruses. How HCMV infection affects this critical pathway is not currently known. In this study, we demonstrate that HCMV dysregulates Wnt/β-catenin signaling in dermal fibroblasts and human placental extravillous trophoblasts. Infection inhibits Wnt-induced transcriptional activity of β-catenin and expression of β-catenin target genes in these cells. HCMV infection leads to β-catenin protein accumulation in a discrete juxtanuclear region. Levels of β-catenin in membrane-associated and cytosolic pools, as well as nuclear β-catenin, are reduced after infection; while transcription of the β-catenin gene is unchanged, suggesting enhanced degradation. Given the critical role of Wnt/β-catenin signaling in cellular processes, these findings represent a novel and important mechanism whereby HCMV disrupts normal cellular function.

Sequence and transcription analysis of the human cytomegalovirus DNA polymerase gene

International Nuclear Information System (INIS)

Kouzarides, T.; Bankier, A.T.; Satchwell, S.C.; Weston, K.; Tomlinson, P.; Barrell, B.G.

1987-01-01

DNA sequence analysis has revealed that the gene coding for the human cytomegalovirus (HCMV) DNA polymerase is present within the long unique region of the virus genome. Identification is based on extensive amino acid homology between the predicted HCMV open reading frame HFLF2 and the DNA polymerase of herpes simplex virus type 1. The authors present here a 5280 base-pair DNA sequence containing the HCMV pol gene, along with the analysis of transcripts encoded within this region. Since HCMV pol also shows homology to the predicted Epstein-Barr virus pol, they were able to analyze the extent of homology between the DNA polymerases of three distantly related herpes viruses, HCMV, Epstein-Barr virus, and herpes simplex virus. The comparison shows that these DNA polymerases exhibit considerable amino acid homology and highlights a number of highly conserved regions; two such regions show homology to sequences within the adenovirus type 2 DNA polymerase. The HCMV pol gene is flanked by open reading frames with homology to those of other herpes viruses; upstream, there is a reading frame homologous to the glycoprotein B gene of herpes simplex virus type I and Epstein-Barr virus, and downstream there is a reading frame homologous to BFLF2 of Epstein-Barr virus

Phage-display libraries of murine and human antibody Fab fragments

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Engberg, J; Andersen, P S; Nielsen, L K

1996-01-01

We provide efficient and detailed procedures for construction, expression, and screening of comprehensive libraries of murine or human antibody Fab fragments displayed on the surface of filamentous phage. In addition, protocols for producing and using ultra-electrocompetent cells, for producing Fab...

Evidence that phosphatidylcholine-specific phospholipase C is a key molecule mediating insulin-induced enhancement of gene expression from human cytomegalovirus promoter in CHO cells

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Zhang, Yingpei; Katakura, Yoshinori; Seto, Perry; Shirahata, Sanetaka

1997-01-01

The signal transduction from insulin to its receptors and Ras has been extensively studied, while little has been reported beyond these steps. We found that the expression of human interleukin 6 gene under the control of immediate early gene promoter of human cytomegalovirus was enhanced by insulin sitmulation in Chinese hamster ovary cells. The induction effect of insulin was not significantly affected by inhibitors or activators of conventional protein kinase C, cAMP dependent protein kinas...

Evaluation of the synuclein-y (SNCG) gene as a PPARy target in murine adipocytes, dorsal root ganglia somatosensory neurons, and human adipose tissue

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Synuclein-gamma is highly expressed in both adipocytes and peripheral nervous system (PNS) somatosensory neurons. Its mRNA is induced during adipogenesis, increased in obese human white adipose tissue (WAT), may be coordinately regulated with leptin, and is decreased following treatment of murine 3T...

Human cytomegaloviruses expressing yellow fluorescent fusion proteins--characterization and use in antiviral screening.

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Sarah Straschewski

Full Text Available Recombinant viruses labelled with fluorescent proteins are useful tools in molecular virology with multiple applications (e.g., studies on intracellular trafficking, protein localization, or gene activity. We generated by homologous recombination three recombinant cytomegaloviruses carrying the enhanced yellow fluorescent protein (EYFP fused with the viral proteins IE-2, ppUL32 (pp150, and ppUL83 (pp65. In growth kinetics, the three viruses behaved all like wild type, even at low multiplicity of infection (MOI. The expression of all three fusion proteins was detected, and their respective localizations were the same as for the unmodified proteins in wild-type virus-infected cells. We established the in vivo measurement of fluorescence intensity and used the recombinant viruses to measure inhibition of viral replication by neutralizing antibodies or antiviral substances. The use of these viruses in a pilot screen based on fluorescence intensity and high-content analysis identified cellular kinase inhibitors that block viral replication. In summary, these viruses with individually EYFP-tagged proteins will be useful to study antiviral substances and the dynamics of viral infection in cell culture.

Cytomegalovirus Infection among Infants in California Neonatal Intensive Care Units, 2005–2010

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Lanzieri, Tatiana M.; Bialek, Stephanie R.; Bennett, Mihoko V.; Gould, Jeffrey B.

2016-01-01

Aim Assess the burden of congenital and perinatal cytomegalovirus (CMV) disease among infants hospitalized in neonatal intensive care units (NICUs). Methods CMV infection was defined as a report of positive CMV viral culture or PCR at any time since birth in an infant hospitalized in a NICU reporting to California Perinatal Quality Care Collaborative during 2005–2010. Results 156 (1.7 per 1000) infants were reported with CMV infection, representing an estimated 5% of the expected number of live births with symptomatic CMV disease. Prevalence was higher among infants with younger gestational ages and lower birth weights. Infants with CMV infection had significantly longer hospital stays; 14 (9%) died. Conclusions Reported prevalence of CMV infection in NICUs represents a fraction of total expected disease burden from CMV in the newborn period, likely resulting from underdiagnosis and milder symptomatic cases that do not require NICU care. More complete ascertainment of infants with congenital CMV infection that would benefit from antiviral treatment may reduce the burden of CMV disease in this population. PMID:24334425

Fatal congenital cytomegalovirus infection following recurrent maternal infection after a 7-year interval

International Nuclear Information System (INIS)

Ergun, U. Guney; Bakaris, S.; Ucmak, H.; Ozbeck, A.

2007-01-01

It is generally accepted that the risk for fetal infection is greatest with maternal primary cytomegalovirus (CMV) infection and much less likely with recurrent infection. Here, we report a fatal case of congenital CMV infection following recurrent maternal infectious after a 7-year interval. A 3-months-old female baby presented with fever, jaundice, vomiting and stopping breast-feeding. Physical examination revealed mild respiratory distress, hepatosplenomegaly, microcephaly and growth retardation. Laboratory examination included bilirubin concentrations (total 7.17 mg/dl; conjugated 6.67 mg/dl), aspartate transaminase (141 IU), and alanine transminase (141 IU), and alanine transminase (499 IU). Enzyme linked immunosorbent assay test results revealed (+) CMV IgM and (+) CMV IgG. She died on the 10 th day of admission with the diagnosis of CMV hepatitis, pneumonia and multi-organ failure. Nuclear and cytoplasmic inclusions demonstrated in the lung, liver and brain on postmortem biopsy. This case highlights that the outcome of babies born to mothers with recurrent maternal CMV infection may be more severe and fatal than previously thought. (author)

Peritoneal macrophages mediated delivery of chitosan/siRNA nanoparticle to the lesion site in a murine radiation-induced fibrosis model

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Nawroth, Isabel; Alsner, Jan; Deleuran, B.W.

2013-01-01

of chitosan/siRNA nanoparticles directed towards silencing TNF alpha in local macrophage populations, but the mechanism for the therapeutic effect at the lesion site remains unclear. Methods. Using the same murine RIF model we utilized an optical imaging technique and fluorescence microscopy to investigate...... the uptake of chitosan/fluorescently labeled siRNA nanoparticles by peritoneal macrophages and their subsequent migration to the inflamed tissue in the RIF model. Results. We observed strong accumulation of the fluorescent signal in the lesion site of the irradiated leg up to 24 hours using the optical...... imaging system. We further confirm by immunohistochemical staining that Cy3 labeled siRNA resides in macrophages of the irradiated leg. Conclusion. We provide a proof-of-concept for host macrophage trafficking towards the inflamed region in a murine RIF model, which thereby suggests that the chitosan...

Comparison of vectorial ion transport in primary murine airway and human sinonasal air-liquid interface cultures, models for studies of cystic fibrosis, and other airway diseases.

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Zhang, Shaoyan; Fortenberry, James A; Cohen, Noam A; Sorscher, Eric J; Woodworth, Bradford A

2009-01-01

The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium. Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport. The change in forskolin-stimulated current (delta-I(SC), expressed as micro-A/cm(2)) in murine septal (n = 19; 16.84 +/- 2.09) and human sinonasal (n = 18; 12.15 +/- 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 +/- 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated I(SC) was inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 microM). No forskolin-stimulated I(SC) was shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal I(SC) was largely inhibited by amiloride (12.03 +/- 0.66), whereas human sinonasal cultures had a very limited response (0.70 +/- 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 +/- 1.28; human sinonasal, 11.12 +/- 1.58; murine trachea, 4.85 +/- 0.49; p < 0.0001). Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.

[The comparison of two newborn cytomegalovirus IgG antibody screening ELISA kits].

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Zhang, Shun-Xian; He, Xiao-Zhou; Wang, Shi-Wen; Wang, Xiao-Fang

2013-10-01

This study compared two newborn Cytomegalovirus (CMV) IgG antibody screening ELISA kits and evaluated the detection effectiveness of Abnova kit. CMV IgG antibodies were detected by both SeraQuest and Abnova kits from dried blood spot (DBS) samples of 488 newborn heel sticks. The detection abilities of these two kits were compared in different sample dilution concentrations. Relative detection effectiveness of the Abnova kit was defined by statistical method using the SeraQuest kit as a point of comparison. Compared to the SeraQuest screening test kit, the Abnova kit revealed a sensitivity of 98.9%, specificity of 78.6%, positive predictive value of 99.3%, negative predictive value of 68.8%, and the coincidence rate for these two screening test kits at 98.3%. The consistency check of both kits based on interpretation of the kappa statistic was relatively good. For the Abnova kit, the "area under the ROC curve" was 0.887, which indicates moderate accuracy. Abnova kit can be applied to newborn screening for congenital CMV infections. However, repeating the test for ambiguous results is suggested to increase the specificity and negative predictive value.

Turnover of T cells in murine gammaherpesvirus 68-infected mice

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Hamilton-Easton, A M; Christensen, Jan Pravsgaard; Doherty, P C

1999-01-01

Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found...

Local IL-23 expression in murine vaginal candidiasis and its relationship with infection and immune status.

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Wu, Yan; Tan, Zhijian; Liu, Zhixiang; Xia, Dechao; Li, Jiawen

2006-01-01

To investigate the expression of vaginal IL-23 and its role in experimental murine vaginal candidiasis and its relationship with infection and immune status, immuno-competent (group A) and immuno-suppressed (group B) murine models of vaginal candidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls (group C). The level of IL-23 p19 mRNA in murine vaginal tissue was determined by RT-PCR. Significantly increased levels of IL-23p19mRNA were observed on the 4th, the 7th and 14th day after inoculation in immuno-competent group when compared with that in control group (Pvaginal candidiasis and has a protective function during infection. Low vaginal IL-23 level may correlate with the increased susceptibility to Candida albicans in immuno-suppressed group.

Severe cytomegalovirus infections in immunocompetent patients at admission as dengue mimic: successful treatment with intravenous ganciclovir.

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Tirumala, Suhasini; Behera, Bijayini; Lingala, Shilpa; Kumar, B Vijay; Mishra, Pradeep Kumar; Gurunath, J M; HariCharan; Kartik; Naresh

2012-11-01

Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons. The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lacking evidence of immunosuppression at ICU admission has received great attention in the practice of critical care medicine. Critically ill patients in ICU who had associated risk factors such as mechanical ventilation, severe sepsis, or blood transfusion are more prone to CMV activation, which in turn led to increased mortality and morbidity in terms of increased ICU stay, longer duration of mechanical ventilation, and higher rates of nosocomial infections. However, severe CMV as initial presentation mimicking dengue infection is rare. We recently came across seven cases with positive CMV serology at ICU admission, which we discuss in the light of current literature. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915 Team.

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Holland, G N; Levinson, R D; Jacobson, M A

1995-05-01

A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs. Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups. The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 microns/day; P = .031). Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.

Sex differences in the MB49 syngeneic, murine model of bladder cancer.

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White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M

The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro . MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro . The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice.

Current concepts on cytomegalovirus infection after liver transplantation.

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Lee, Sang-Oh; Razonable, Raymund R

2010-09-27

Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, valganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. In this article, the authors review the

Methamphetamine Administration Modifies Leukocyte Proliferation and Cytokine Production in Murine Tissues

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Peerzada, Habibullah; Ghandi, Jay A.; Guimaraes, Allan J.; Nosanchuk, Joshua D.; Martinez, Luis R.

2013-01-01

Methamphetamine (METH) is a potent and highly addictive central nervous system (CNS) stimulant. Additionally, METH adversely impacts immunological responses, which might contribute to the higher rate and more rapid progression of certain infections in drug abusers. However no studies have shown the impact of METH on inflammation within specific organs, cellular participation and cytokine production. Using a murine model of METH administration, we demonstrated that METH modifies, with variable degrees, leukocyte recruitment and alters cellular mediators in the lungs, liver, spleen and kidneys of mice. Our findings demonstrate the pleotropic effects of METH on the immune response within diverse tissues. These alterations have profound implications on tissue homeostasis and the capacity of the host to respond to diverse insults, including invading pathogens. PMID:23518444

Newly Characterized Murine Undifferentiated Sarcoma Models Sensitive to Virotherapy with Oncolytic HSV-1 M002

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Eric K. Ring

2017-12-01

Full Text Available Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45 and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1. Both models expressed high levels of the primary HSV entry molecule nectin-1 (CD111 and were susceptible to killing by interleukin-12 (IL-12 producing HSV-1 M002 in vitro and in vivo. M002 resulted in a significant intratumoral increase in effector CD4+ and CD8+ T cells and activated monocytes, and a decrease in myeloid-derived suppressor cells (MDSCs in immunocompetent mice. Compared to parent virus R3659 (no IL-12 production, M002 resulted in higher CD8:MDSC and CD8:T regulatory cell (Treg ratios, suggesting that M002 creates a more favorable immune tumor microenvironment. These data provide support for clinical trials targeting sarcomas with oncolytic HSV-1. These models provide an exciting opportunity to explore combination therapies for soft tissue sarcomas that rely on an intact immune system to reach full therapeutic potential.

Development of a murine model of acute radiation encephalopathy

International Nuclear Information System (INIS)

Xing Yigang; Tang Yamei; Liu Jun; Sun Ying

2003-01-01

Objective: To develop a murine model of acute radiation encephalopathy. Methods: A total of 40 rats were subjected to local γ-irradiation to the brain with the dosage of 7 Gy/d for 6 consecutive days. The amount of food intake, hairs and skin of irradiated field, body weight, general activities, CNS symptoms and signs were examined and recorded after irradiation. On day 3, 7, 14 and 30, the brain tissue was removed to observe histopathologic changes. Results: During the first two days after irradiation, the irradiated rats were agitated, and the amount of food intake decreased from day 2 onwards. No serious skin reaction to irradiation was observed. Survived rats had normal activities without any abnormal nervous signs. Histopathologic changes showed slight neuronal degeneration, smaller cell body, red-colored cytoplasm, disappearance of Nissl body, vacuolation, typical cell shrinkage, chromatin condensation and nuclear divergence. On the 14th and 30th days, hypochromatism, loose and reticular necrotic foci were found in some samples. Conclusion: The murine model of acute radiation encephalopathy is useful and practical in radiobiological studies

Comparison of the Histopaque-1119 method with the Plasmagel method for separation of blood leukocytes for cytomegalovirus isolation.

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Slifkin, M; Cumbie, R

1992-10-01

Histopaque-1119 (Sigma Chemical Co., St. Louis, Mo.) and Plasmagel (Cellular Products, Inc., Buffalo, N.Y.) were compared as density gradient separation reagents for the separation of polymorphonuclear leukocytes and mononuclear cells from blood from the isolation of cytomegalovirus (CMV). Of 200 peripheral blood specimens examined, CMV was recovered from 51 by both methods. The time of detection of immunofluorescent sites or a cytopathic effect associated with CMV was similar by each method. The Histopaque-1119 method was less time-consuming than the Plasmagel method since it did not require a precentrifugation step for the settling of erythrocytes. The use of Histopaque-1119 will permit an effective alternative single-step method for the separation of blood leukocytes for the isolation of CMV.

The cytomegalovirus homolog of interleukin-10 requires phosphatidylinositol 3-kinase activity for inhibition of cytokine synthesis in monocytes.

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Spencer, Juliet V

2007-02-01

Human cytomegalovirus (CMV) has evolved numerous strategies for evading host immune defenses, including piracy of cellular cytokines. A viral homolog of interleukin-10, designated cmvIL-10, binds to the cellular IL-10 receptor and effects potent immune suppression. The signaling pathways employed by cmvIL-10 were investigated, and the classic IL-10R/JAK1/Stat3 pathway was found to be activated in monocytes. However, inhibition of JAK1 had little effect on cmvIL-10-mediated suppression of tumor necrosis factor alpha (TNF-alpha) production. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway had a more significant impact on TNF-alpha levels but did not completely relieve the immune suppression, demonstrating that cmvIL-10 stimulates multiple signaling pathways to modulate cell function.

JST Thesaurus Headwords and Synonyms: murine hepatitis virus [MeCab user dictionary for science technology term[Archive

Lifescience Database Archive (English)

Full Text Available MeCab user dictionary for science technology term murine hepatitis virus 名詞 一般 * * * * マウス肝炎...ウイルス マウスカンエンウイルス マウスカンエンウイルス Thesaurus2015 200906024862381907 C LS07 UNKNOWN_2 murine hepatitis virus

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

Science.gov (United States)

Permar, Sallie R.; Plotkin, Stanley A.

2017-01-01

ABSTRACT A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice. PMID:29046308

Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Gabriel Westman

Full Text Available Alzheimer's disease (AD has been associated with increased local inflammation in the affected brain regions, and in some studies also with elevated levels of proinflammatory cytokines in peripheral blood. Cytomegalovirus (CMV is known to promote a more effector-oriented phenotype in the T-cell compartment, increasing with age. The aim of this study was to investigate the inflammatory response of peripheral blood mononuclear cells (PBMCs from AD patients and non-demented (ND controls. Using a multiplex Luminex xMAP assay targeting GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10 and TNF-α, cytokine profiles from PBMCs were analysed after stimulation with anti-CD3/CD28 beads, CMV pp65 peptide mix or amyloid β (Aβ protofibrils, respectively. CMV seropositive AD subjects presented with higher IFN-γ levels after anti-CD3/CD28 and CMV pp65 but not after Aβ stimulation, compared to CMV seropositive ND controls. When analysing IFN-γ response to anti-CD3/CD28 stimulation on a subgroup level, CMV seropositive AD subjects presented with higher levels compared to both CMV seronegative AD and CMV seropositive ND subjects. Taken together, our data from patients with clinically manifest AD suggest a possible role of CMV as an inflammatory promoter in AD immunology. Further studies of AD patients at earlier stages of disease, could provide better insight into the pathophysiology.

Polymeric mannosides prevent DC-SIGN-mediated cell-infection by cytomegalovirus.

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Brument, S; Cheneau, C; Brissonnet, Y; Deniaud, D; Halary, F; Gouin, S G

2017-09-20

Human cytomegalovirus (HCMV) is a beta-herpesvirus with a high prevalence in the population. HCMV is asymptomatic for immunocompetent adults but is a leading cause of morbidity for new born and immunocompromised patients. It was recently shown that the envelope glycoprotein B (gB) of HCMV interacts with the Dendritic Cell-Specific ICAM-3 Grabbing Non integrin (DC-SIGN) to infect the host. In this work we developed a set of DC-SIGN blockers based on mono-, di-, tetra and polyvalent mannosides. The multivalent mannosides were designed to interact with the carbohydrate recognition domains of DC-SIGN in a chelate or bind and recapture process, and represent the first chemical antiadhesives of HCMV reported so far. Polymeric dextrans coated with triazolylheptylmannoside (THM) ligands were highly potent, blocking the gB and DC-SIGN interaction at nanomolar concentrations. The compounds were further assessed for their ability to prevent the DC-SIGN mediated HCMV infection of dendritic cells. A dextran polymer coated with an average of 902 THM ligands showed an outstanding effect in blocking the HCMV trans-infection with IC 50 values down to the picomolar range (nanomolar when expressed in THM concentration). Each THM moiety on the polymer surpassed the antiadhesive effect of the methylmannoside reference by more than four orders of magnitude. The compound proved non-cytotoxic at the high concentration of 2 mM and therefore represents an interesting antiadhesive candidate against HCMV and potentially against other virus hijacking dendritic cells to infect the host.

Contemplating the murine test tube: lessons from natural killer cells and Cryptococcus neoformans.

Science.gov (United States)

Marr, Kaleb J; Jones, Gareth J; Mody, Christopher H

2006-06-01

Murine experimentation has provided many useful tools, including the ability to knockout or over-express genes and to perform experiments that are limited by ethical considerations. Over the past century, mice have imparted valuable insights into the biology of many systems, including human immunity. However, although there are many similarities between the immune response of humans and mice, there are also many differences; none is more prominent than when examining natural killer cell biology. These differences include tissue distribution, effector molecules, receptor repertoire, and cytokine responses, all of which have important implications when extrapolating the studies to the human immune responses to Cryptococcus neoformans.

[Nuclear matrix organization of the chromocenters in cultured murine fibroblasts].

Science.gov (United States)

Sheval', E V; Poliakov, V Iu

2010-01-01

In the current work, the structural organization of nuclear matrix of pericentromeric heterochromatin blocks (chromocenters) inside cultured murine fibroblasts was investigated. After 2 M NaCl extraction without DNase I treatment, chromocenters were extremely swelled, and it was impossible to detect them using conventional electron microscopy. Using immunogolding with anti-topoisomerase IIalpha antibody, we demonstrated that residual chromocenters were subdivided into numerous discrete aggregates. After 2 M NaCl extraction with DNase I treatment, the residual chromocenters appeared as a dense meshwork of thin fibers, and using this feature, the residual chromocenters were easily distinguished from the rest of nuclear matrix. After extraction with dextran sulfate and heparin, the chromocenters were decondensed, and chromatin complexes having rosette organization (central core from which numerous DNA fibers radiated) were seen. Probably, the appearance of these rosettes was a consequence of incomplete chromatin extraction. Thus, the nuclear matrix of pericentromeric chromosome regions in cultured murine fibroblasts differs morphologically from the rest of nuclear matrix.

Cytoplasmic superoxide dismutase and catalase activity and resistance to radiation lethality in murine tumor cells

International Nuclear Information System (INIS)

Davy, C.A.; Tesfay, Z.; Jones, J.; Rosenberg, R.C.; McCarthy, C.; Rosenberg, S.O.

1986-01-01

Reduced species of molecular oxygen are produced by the interaction of ionizing radiation with aqueous solutions containing molecular oxygen. The enzymes catalase and superoxide dismutase (SOD) are thought to function in vivo as scavengers of metabolically produced peroxide and superoxide respectively. SOD has been shown to protect against the lethal effects of ionizing radiation in vitro and in vivo. The authors have investigated the relationship between the cytosolic SOD catalase content and the sensitivity to radiation lethality of a number of murine cell lines (402AX, EL-4, MB-2T3, MB-4, MEL, P-815, SAI, SP-2, and SV-3T3). K/sub i/(CN - ) for murine Cu-Zn-SOD was determined to be 6.8 x 10 -6 M. No cytosolic Mn-SOD activity was found in any of the cell lines studied. No correlation was found between the cytosolic Cu-Zn-SOD or cytosolic catalase activity and the resistance to radiation lethality or the murine cell lines studied

Cholestasis caused by panhypopituitarism and acquired cytomegalovirus infection in a 2-month-old male infant

Science.gov (United States)

Chan, U; Chan, Wai-Tao; Ting, Wei-Hsin; Ho, Che-Sheng; Liu, Hsi-Che; Lee, Hung-Chang

2017-01-01

Abstract Rationale: Septo-optic dysplasia (SOD) is a rare congenital disorder that may cause jaundice in infants. However, it is usually prone to neglect and misdiagnosis in infants with cholestasis because endocrine disorder such as panhypopituitarism is rare in the cause of infantile cholestasis. We report a case of SOD concurrent with acquired cytomegalovirus (CMV) infection, who presented with prolonged jaundice as the first clinical sign. Patient concerns: The patient was a 2-month-old male infant who presented with cholestasis, combined with fever and panhypopituitarism. Diagnoses: He was diagnosed with SOD and acquired CMV infection. Interventions: He was treated with hormone replacement therapy and ganciclovir. Outcomes: After correction of the pituitary hormone deficiency and ganciclovir treatment, significant improvements of cholestasis, retinal lesions, and growth rate were seen in our patient. Lessons: Although an endocrine disorder such as panhypopituitarism is rare in the cause of neonatal or infantile cholestasis, we must keep this reason in mind. PMID:28445302

Ganciclovir-Resistant Cytomegalovirus Infection in a Kidney Transplant Recipient Successfully Treated with Foscarnet and Everolimus.

Science.gov (United States)

Menghi, Viola; Comai, Giorgia; Baraldi, Olga; Liviano D'Arcangelo, Giovanni; Lazzarotto, Tiziana; La Manna, Gaetano

2016-01-01

Cytomegalovirus (CMV) infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV-) resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient's viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection.

Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes pancreatitis and apoptotic cell death

Science.gov (United States)

Athwal, T; Huang, W; Mukherjee, R; Latawiec, D; Chvanov, M; Clarke, R; Smith, K; Campbell, F; Merriman, C; Criddle, D; Sutton, R; Neoptolemos, J; Vlatković, N

2014-01-01

Hereditary pancreatitis (HP) is an autosomal dominant disease that displays the features of both acute and chronic pancreatitis. Mutations in human cationic trypsinogen (PRSS1) are associated with HP and have provided some insight into the pathogenesis of pancreatitis, but mechanisms responsible for the initiation of pancreatitis have not been elucidated and the role of apoptosis and necrosis has been much debated. However, it has been generally accepted that trypsinogen, prematurely activated within the pancreatic acinar cell, has a major role in the initiation process. Functional studies of HP have been limited by the absence of an experimental system that authentically mimics disease development. We therefore developed a novel transgenic murine model system using wild-type (WT) human PRSS1 or two HP-associated mutants (R122H and N29I) to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. The rat elastase promoter was used to target transgene expression to pancreatic acinar cells in three transgenic strains that were generated: Tg(Ela-PRSS1)NV, Tg(Ela-PRSS1*R122H)NV and Tg(Ela-PRSS1*N29I)NV. Mice were analysed histologically, immunohistochemically and biochemically. We found that transgene expression is restricted to pancreatic acinar cells and transgenic PRSS1 proteins are targeted to the pancreatic secretory pathway. Animals from all transgenic strains developed pancreatitis characterised by acinar cell vacuolisation, inflammatory infiltrates and fibrosis. Transgenic animals also developed more severe pancreatitis upon treatment with low-dose cerulein than controls, displaying significantly higher scores for oedema, inflammation and overall histopathology. Expression of PRSS1, WT or mutant, in acinar cells increased apoptosis in pancreatic tissues and isolated acinar cells. Moreover, studies of isolated acinar cells demonstrated that transgene expression promotes apoptosis rather than necrosis. We therefore

Morphological changes in the digestive system of 322 necropsies of patients with acquired immune deficiency syndrome: comparison of findings pre- and post-HAART (Highly Active Antiretroviral Therapy

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Lucinda Calheiros Guimarães

Full Text Available ABSTRACT Involvement of the digestive system in AIDS pathologies or injuries is frequent. Aiming at comparing the frequency, the importance that these lesions have for death and the survival time in patients using or not using HAART, we studied 322 necropsies classified as follows: Group A - without antiretroviral drugs (185 cases; B - one or two antiretroviral drugs or HAART for less than six months (83 cases; C - HAART for six months or longer (54 cases. In the overall analysis of the digestive system, changes were present in 73.6% of cases. The most frequent was Candida infection (22.7%, followed by cytomegalovirus (19.2%, Histoplasma capsulatum (6.5%, mycobacteria (5.6%, and Toxoplasma gondii (4.3%. T. gondii infection was more frequent in group A compared with group C, and cytomegalovirus (CMV was more frequent in group A compared with groups B and C (p < 0.05; 2.2% of the deaths were due to gastrointestinal bleeding. Regarding the segments, only in the large intestine, and only cytomegalovirus, were more frequent in group A compared with group C. We conclude that digestive system infections are still frequent, even with the use of HAART. However, the average survival time in group C was more than three times greater than the one in group A and nearly double that of group B, demonstrating the clear benefit of this therapy.

Cytomegalovirus infection after liver transplantation: Current concepts and challenges

Institute of Scientific and Technical Information of China (English)

Raymund Rabe Razonable

2008-01-01

Cytomegalovirus(CMV)is a common viral pathogen that influences the outcome of liver transplantation.In addition to the direct effects of CMV syndrome and tissue-invasive diseases,CMV is associated with an increased predisposition to acute and chronic allograft rejection,accelerated hepatitis C recurrence,and other opportunistic infections,as well as reduced overall patient and allograft survival.Risk factors for CMV disease are often interrelated,and include CMV D+/R-serostatus,acute rejection,female gender,age,use of high-dose mycophenolate mofetil and prednisone,and the overall state of immunity.In addition to the role of CHV-specific CD4+ and CD8+ T lymphocytes,there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis.In one study,liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher Ievels of CMV replication and clinical disease.Because of the direct and indirect adverse effects of CMV disease,its prevention,whether through antiviral prophylaxis or preemptive therapy,is an essential component in improving the outcome of liver transplantation.In the majority of transplant centers,antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-).However,the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease.In several prospective and retrospective studies,the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation.Therefore,optimized strategies for prevention and novel drugs with unique modes of action are needed.Currently,a randomized controlled clinical trial is being

MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8

DEFF Research Database (Denmark)

Lüttichau, H R; Gerstoft, J; Schwartz, T W

2001-01-01

The viral CC chemokines MC148, encoded by the poxvirus molluscum contagiosum, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in parallel with human CCR8. In calcium mobilization assays, vMIP-I acted...... as a high-affinity agonist, whereas vMIP-II acted as a low-affinity antagonist on the murine CCR8 as well as the human CCR8. MC148 was found to bind and block responses through the human CCR8 with high affinity, but surprisingly MC148 was unable to bind and block responses through the murine CCR8. Because...

Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression.

Directory of Open Access Journals (Sweden)

Katharina Galmbacher

Full Text Available A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDeltaaroA and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TDeltaaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

Radiobiological studies on target cell populations in murine bone marrow transplantation recipients.

NARCIS (Netherlands)

van Os, Ronald Peter

1994-01-01

The experiments presented in this thesis were designed to investigate the role of total body irradiation (TBI) in conditioning murine recipients of syngeneic and allogeneic bone marrow transplantation (BMT). ... Zie: Summary

Responses of the Murine Myeloid Colony-Forming Cell to Ansamycin Antibiotics

Science.gov (United States)

Horoszewicz, Julius S.; Carter, William A.

1974-01-01

The in vitro susceptibility of murine myeloid colony-forming cells to the antiproliferative activities of three ansamycin antibiotics was determined. These cells were found to be 10- to 40-fold more susceptible than the corresponding human ones. PMID:4151701

JST Thesaurus Headwords and Synonyms: murine leukemia virus [MeCab user dictionary for science technology term[Archive

Lifescience Database Archive (English)

Full Text Available MeCab user dictionary for science technology term murine leukemia virus 名詞 一般 * * *... * マウス白血病ウイルス マウスハッケツビョウウイルス マウスハッケツビョーウイルス Thesaurus2015 200906060491156251 C LS07 UNKNOWN_2 murine leukemia virus

Transgene stability for three replication competent murine leukemia virus vectors

DEFF Research Database (Denmark)

Duch, M.; Carrasco, M.L.; Jespersen, T.

2004-01-01

cassette consisting of an internal ribosome entry site followed by the enhanced green fluorescent protein coding sequence inserted in different configurations into murine leukemia virus genomes. In two of the constructs, the insert was located in the upstream part of the U3 region while in the third...

Case report

African Journals Online (AJOL)

abp

Key words: Systemic lupus erythematous, cerebral vasculitis, cytomegalovirus infection. Received: 31/01/2016 - Accepted: 23/05/2016 - Published: 15/07/2016. Abstract. Cytomegalovirus (CMV) infection have been described as exacerbing systemic lupus erythematous (SLE). The role of CMV in starting off SLE remains ...