Publications

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 ...	2009	19214440
expression of newly identified secretory ceacam1(a) isoforms in the intestinal epithelium.	carcinoembryonic antigen-related cell adhesion molecule 1 (ceacam1) regulates intestinal immunological homeostasis. however, precise expression patterns of ceacam1 isoforms remain poorly understood in the intestinal epithelia. focusing on the small intestinal epithelium of balb/c mice, we identified three novel splice variants encoding ceacam1(a)-2, -2c1, and -4c1 by rt-pcr. ceacam1(a)-2, -2c1, and -4c1 demonstrated secretory properties by transfection experiments in vitro. among them, ceacam1(a ...	2009	19358828
target-dependent b7-h1 regulation contributes to clearance of central nervous system infection and dampens morbidity.	the neurotropic coronavirus jhm strain of mouse hepatitis virus persists in oligodendroglia despite the presence of virus-specific cd8 t cells. expression of programmed death 1 (pd-1) and b7-h1 were studied during acute and persistent infection to examine whether this negative regulatory mechanism contributes to cns viral persistence. the majority of cns-infiltrating cd8 t cells expressed pd-1, with the highest levels on virus-specific cd8 t cells. moreover, despite control of infectious virus, ...	2009	19380790
development of a chimeric dna-rna hammerhead ribozyme targeting sars virus.	severe acute respiratory syndrome (sars) is a severe pulmonary infectious disease caused by a novel coronavirus. to develop an effective and specific medicine targeting the sars-coronavirus (cov), a chimeric dna-rna hammerhead ribozyme was designed and synthesized using a sequence homologous with the mouse hepatitis virus (mhv).	2009	19420961
cxcl10 and trafficking of virus-specific t cells during coronavirus-induced demyelination.	chronic expression of cxc chemokine ligand 10 (cxcl10) in the central nervous system (cns) following infection with the neurotropic jhm strain of mouse hepatitis virus (jhmv) is associated with an immune-mediated demyelinating disease. treatment of mice with anti-cxcl10 neutralizing antibody results in limited cd4+ t cell infiltration into the cns accompanied by a reduction in white matter damage. the current study determines the antigen-specificity of the t lymphocytes present during chronic di ...	2009	19626487
a serological survey to evaluate contemporary prevalence of viral agents and mycoplasma pulmonis in laboratory mice and rats in western europe.	to evaluate current prevalence rates of 24 viruses and of the bacterium mycoplasma pulmonis, the authors retrospectively surveyed serological data obtained from laboratory mice and rats housed in more than 100 western european institutions. serum samples were submitted to the authors' institution for testing between january 2007 and june 2008. the prevalence of an infection was defined as the percentage of tested samples that yielded positive results for a specific agent. in mice, the most commo ...	2009	19384313
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 ...	2010	20534452
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 ...	2010	20370625
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 ...	2010	20484516
murine coronavirus receptors are differentially expressed in the central nervous system and play virus strain-dependent roles in neuronal spread.	coronavirus infection of the murine central nervous system (cns) provides a model for studies of viral encephalitis and demyelinating disease. mouse hepatitis virus (mhv) neurotropism varies by strain: mhv-a59 causes mild encephalomyelitis and demyelination, while the highly neurovirulent strain jhm.sd (mhv-4) causes fatal encephalitis with extensive neuronal spread of virus. in addition, while neurons are the predominant cns cell type infected in vivo, the canonical receptor for mhv, the carcin ...	2010	20739537
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/ ...	2010	20130062
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 ...	2010	20978536
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 ...	2010	19949088
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 ...	2010	20007284
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 ...	2011	21508117
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 ...	2011	21572336
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 ...	2011	21775959
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 ...	2011	21752960
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 ...	2011	21924228
receptor tyrosine kinase inhibitors that block replication of influenza a and other viruses.	we have previously reported that two receptor tyrosine kinase inhibitors (rtkis), called ag879 and tyrphostin a9 (a9), can each block the replication of influenza a virus in cultured cells. in this study, we further characterized the in vitro antiviral efficacies and specificities of these agents. the 50% effective concentration (ec(50)) of each against influenza a was found to be in the high nanomolar range, and the selectivity index (si = 50% cytotoxic concentration [cc(50)]/ec(50)) was determ ...	2011	21930873
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 ...	2012	22232667
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 ...	2014	25502736