Publications

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 ...	2009	19652715
microbial contaminations of laboratory mice and rats in taiwan from 2004 to 2007.	limited data are available on the pathogen status of contemporary rodent colonies in taiwan. here we summarized the rodent pathogen diagnostic records of the taiwan national laboratory animal center during a 4-y period that representing approximately 10% of the rodent colonies in taiwan. demand for pathogen diagnostic service increased continuously from 2004 to 2007, with a 20% increase each year. in 2007, more than 20% of the mouse colonies were positive for mouse parvovirus, mouse hepatitis vi ...	2009	19653946
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 ...	2009	19706706
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 ...	2009	19811085
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 ...	2009	19887025
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
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
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
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
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
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
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 ...	1998	21374459
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
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
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
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