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a novel cre recombinase imaging system for tracking lymphotropic virus infection in vivo.detection, isolation, and identification of individual virus infected cells during long term infection are critical to advance our understanding of mechanisms of pathogenesis for latent/persistent viruses. however, current approaches to study these viruses in vivo have been hampered by low sensitivity and effects of cell-type on expression of viral encoded reporter genes. we have designed a novel cre recombinase (cre)-based murine system to overcome these problems, and thereby enable tracking an ...200919652715
increased killing of liver nk cells by fas/fas ligand and nkg2d/nkg2d ligand contributes to hepatocyte necrosis in virus-induced liver failure.the role of liver nk cells in virus-induced severe viral hepatitis and, subsequently, hepatic failure is not well defined. in this study, we investigated the role of liver nk cells in the development of hepatocyte necrosis in fulminant hepatic failure (fhf) and acute-on-chronic liver failure (aclf) because of viral infection. a mouse model of fhf induced by murine hepatitis virus strain 3 (mhv-3) was used to study the role of liver nk cells. samples from patients with hepatitis b virus-related a ...201019949088
two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis.the coronaviruses mouse hepatitis virus type 2 (mhv-2) and severe acute respiratory syndrome coronavirus (sars-cov) utilize proteases to enter host cells. upon receptor binding, the spike (s) proteins of both viruses are activated for membrane fusion by proteases, such as trypsin, present in the environment, facilitating virus entry from the cell surface. in contrast, in the absence of extracellular proteases, these viruses can enter cells via an endosomal pathway and utilize endosomal cathepsin ...200919706706
fine specificity of autoantibodies induced by mouse hepatitis virus a59.we have shown that mice infected with mouse hepatitis virus a59 (mhv-a59) develop autoantibodies (autoab) to liver and kidney fumarylacetoacetate hydrolase (fah). the autoab recognized conformational as well as linear antigenic determinants in the enzyme, and the autoimmune response was not entirely restricted to molecular mimicry and/or epitope spreading. since the n- and c-terminal portions of the enzyme were the most reactive with autoab, the fine specificity of these ab was investigated. imm ...200919811085
infectious diseases in wild mice (mus musculus) collected on and around the university of pennsylvania (philadelphia) campus.laboratory mice serve as important models in biomedical research. monitoring these animals for infections and infestations and excluding causative agents requires extensive resources. despite advancements in detection and exclusion over the last several years, these activities remain challenging for many institutions. the infections and infestations present in laboratory mouse colonies are well documented, but their mode of introduction is not always known. one possibility is that wild rodents l ...200919887025
pathogenesis of a model gammaherpesvirus in a natural host.murine gammaherpesvirus 68 (mhv-68) infection of laboratory mice (mus musculus) is an established model of gammaherpesvirus pathogenesis. the fact that m. musculus is not a host in the wild prompted us to reassess mhv-68 infection in wood mice (apodemus sylvaticus), a natural host. here, we report significant differences in mhv-68 infection in the two species: (i) following intranasal inoculation, mhv-68 replicated in the lungs of wood mice to levels approximately 3 log units lower than in balb/ ...201020130062
the murine coronavirus nucleocapsid gene is a determinant of virulence.the murine coronavirus, mouse hepatitis virus (mhv) strain a59, causes acute encephalitis and chronic demyelinating disease as well as hepatitis in mice. the jhm strain (also called mhv-4 or jhm.sd) causes fatal encephalitis and only minimal hepatitis. previous analysis of chimeric recombinant mhvs in which the spike gene, encoding the protein that mediates viral entry and cell-to-cell fusion, was exchanged between jhm and a59 showed that the spike plays a major role in determining organ tropism ...201020007284
the pathogenesis of murine coronavirus infection of the central nervous system.mouse hepatitis virus (mhv) is a positive-strand rna virus that causes an acute encephalomyelitis that later resolves into a chronic fulminating demyelinating disease. cytokine production, chemokine secretion, and immune cell infiltration into the central nervous system are critical to control viral replication during acute infection. despite potent antiviral t-lymphocyte activity, sterile immunity is not achieved, and mhv chronically persists within oligodendrocytes. continued infiltration and ...201020370625
the proteasome inhibitor velcade enhances rather than reduces disease in mouse hepatitis coronavirus-infected mice.many viruses, including coronaviruses (covs), depend on a functional cellular proteasome for efficient infection in vitro. hence, the proteasome inhibitor velcade (bortezomib), a clinically approved anticancer drug, shown in an accompanying study (m. raaben et al., j. virol. 84:7869-7879, 2010) to strongly inhibit mouse hepatitis cov (mhv) infection in cultured cells, seemed an attractive candidate for testing its antiviral properties in vivo. surprisingly, however, the drug did not reduce repli ...201020484516
autocrine interferon priming in macrophages but not dendritic cells results in enhanced cytokine and chemokine production after coronavirus infection.coronaviruses efficiently inhibit interferon (ifn) induction in nonhematopoietic cells and conventional dendritic cells (cdc). however, ifn is produced in infected macrophages, microglia, and plasmacytoid dendritic cells (pdc). to begin to understand why ifn is produced in infected macrophages, we infected bone marrow-derived macrophages (bmm) and as a control, bone marrow-derived dc (bmdc) with the coronavirus mouse hepatitis virus (mhv). as expected, bmm but not bmdc expressed type i ifn. ifn ...201020978536
migration of engrafted neural stem cells is mediated by cxcl12 signaling through cxcr4 in a viral model of multiple sclerosis.multiple sclerosis (ms) is a human demyelinating disease characterized by multifocal regions of inflammation, progressive myelin loss within the central nervous system (cns), and eventual failure to remyelinate damaged axons. these problems suggest deficiencies in recruiting and/or maturation of oligodendrocyte progentior cells (opcs) and highlight cell replacement therapies to promote remyelination. we have used a model of viral-induced demyelination to characterize signaling cues associated wi ...201020534452
primary clearance of murine gammaherpesvirus 68 by pkctheta-/- cd8 t cells is compromised in the absence of help from cd4 t cells.cd4 t cells are dispensable for acute control of murine gammaherpesvirus 68 (mhv-68) but are necessary for effective long-term control of the virus by cd8 t cells. in contrast, protein kinase c theta (pkctheta) is not essential for either acute or long-term viral control. however, we found that while either cd4 or cd8 t cells could mediate the clearance of mhv-68 from the lungs of pkctheta(+/+) mice, pkctheta(-/-) mice depleted of either subset failed to clear the virus. these data suggest that ...200818818318
infectious microorganisms in mice (mus musculus) purchased from commercial pet shops in germany.in this study, we investigated the prevalence of infectious microorganisms (viruses, bacteria, fungi and eukaryotic parasites) in mice from different pet shops in germany; such animals may compromise the hygienic integrity of laboratory animal vivaria if private pet holders act as unintended vectors of infections carried by them. house mice sold as pets or feed specimens were purchased from different pet shops and tested for a comprehensive panel of unwanted microorganisms. we found a number of ...201121508117
cyclosporin a inhibits the replication of diverse coronaviruses.low micromolar, non-cytotoxic concentrations of cyclosporin a (csa) strongly affected the replication of sars-coronavirus (sars-cov), human coronavirus 229e, and mouse hepatitis virus in cell culture, as was evident from the strong inhibition of green fluorescent protein reporter gene expression and up to 4 log reduced progeny titres. upon high-multiplicity infection, csa treatment rendered sars-cov rna and protein synthesis almost undetectable, suggesting an early block in replication. sirna-me ...201121752960
macrophage-mediated optic neuritis induced by retrograde axonal transport of spike gene recombinant mouse hepatitis virus.after intracranial inoculation, neurovirulent mouse hepatitis virus (mhv) strains induce acute inflammation, demyelination, and axonal loss in the central nervous system. prior studies using recombinant mhv strains that differ only in the spike gene, which encodes a glycoprotein involved in virus-host cell attachment, demonstrated that spike mediates anterograde axonal transport of virus to the spinal cord. a demyelinating mhv strain induces optic neuritis, but whether this is due to the retrogr ...201121572336
use of lectins for characterization of o-linked glycans of herpes simplex virus glycoproteins.the existence of o-linked glycans in viral glycoproteins was described in the early 1980s for enveloped viruses such as herpes simplex virus type 1 (hsv-1), vaccinia virus, and mouse hepatitis virus (1-4). glycoprotein c of hsv-1 (designated gc-1) was demonstrated to contain domains, in which numerous o-linked glycans were concentrated to pronase-resistant clusters (5-7), thereby resembling the organization of mucins (8). thus glycoprotein, containing nine sites for n-linked glycosylation in add ...199821374459
surgical transplantation of mouse neural stem cells into the spinal cords of mice infected with neurotropic mouse hepatitis virus.mice infected with the neurotropic jhm strain of mouse hepatitis virus (mhv) develop pathological and clinical outcomes similar to patients with the demyelinating disease multiple sclerosis (ms). we have shown that transplantation of nscs into the spinal cords of sick mice results in a significant improvement in both remyelination and in clinical outcome. cell replacement therapies for the treatment of chronic neurologic diseases are now a reality and in vivo models are vital in understanding th ...201121775959
severe gammaherpesvirus-induced pneumonitis and fibrosis in syngeneic bone marrow transplant mice is related to effects of transforming growth factor-β.pulmonary infections and pneumonitis occur frequently after hematopoietic stem cell transplantation. using a syngeneic mouse model of bone marrow transplantation (bmt), we have previously demonstrated that bmt mice are more susceptible to acute gammaherpesvirus 68 (mhv-68) replication at day 7 after infection. by day 21, the virus is latent in lungs of bmt and control mice, and there is no difference in viral load. despite similar latent viral load, bmt mice develop severe pneumonitis associated ...201121924228
type i ifn-mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection.the swift production of type i ifns is one of the fundamental aspects of innate immune responses against viruses. plasmacytoid dendritic cell-derived type i ifns are of prime importance for the initial control of highly cytopathic viruses such as the mouse hepatitis virus (mhv). the aim of this study was to determine the major target cell populations of this first wave of type i ifns. generation of bone marrow-chimeric mice expressing the type i ifn receptor (ifnar) on either hemopoietic or non- ...200919124753
age-dependent pathogenesis of murine gammaherpesvirus 68 infection of the central nervous system.gammaherpesvirus infection of the central nervous system (cns) has been linked to various neurological diseases, including meningitis, encephalitis, and multiple sclerosis. however, little is known about the interactions between the virus and the cns in vitro or in vivo. murine gammaherpesvirus 68 (mhv-68 or (gamma)hv-68) is genetically related and biologically similar to human gammaherpesviruses, thereby providing a tractable animal model system in which to study both viral pathogenesis and rep ...200919214440
microbiological survey of mice (mus musculus) purchased from commercial pet shops in kanagawa and tokyo, japan.information regarding the prevalence of infectious agents in mice in pet shops in japan is scarce. this information is particularly useful for minimizing the risk of potential transmission of infections to laboratory mice. therefore, we surveyed infectious agents in mice from pet shops in kanagawa and tokyo, japan. the survey was conducted in 28 mice from 5 pet shops to screen for 47 items (17 viruses, 22 bacteria and fungi, 10 parasites) using culture tests, serology, pcr, and microscopy. the m ...201425502736
t helper cell- and cd40-dependent germline igm prevents chronic virus-induced demyelinating disease.generation of antiviral igm is usually considered as a marker of a short-lived initial antibody response that is replaced by hypermutated and more-efficient igg. however, once viruses have established a particular niche for their persistence (e.g., within the cns), the immune system has to specifically mobilize a broad range of antimicrobial effectors to contain the pathogen in the long term. infection of the cns with the mouse hepatitis virus (mhv) provides a unique model situation in which the ...201222232667
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