Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse hepatitis virus, strain A59 (MHV-A59), is a coronavirus that triggers in susceptible mice a wide variety of pathologies, including hepatitis, thymus involution, B lymphocyte polyclonal activation and, after intra-cerebral inoculation, transient demyelination. One receptor that mediates entry of the virus into target cells has been identified: it is a glycoprotein of the carcinoembryonic antigen family, called Bgp1a. The availability of antibodies recognizing this molecule permits the analysis of its cellular expression and of the relationship between receptor expression and pathology induced by the virus. Bgp1a is found on epithelial and endothelial cells as well as on B lymphocytes and macrophages. In the liver, Bgp1a expression correlates well with infection of hepatocytes and endothelial cells, leading to the development of hepatitis. However, other cells expressing this molecule, such as central nervous system endothelial cells, are not infected by the virus. This observation may explain how the blood-brain barrier prevents dissemination of MHV-A59 from the general circulation into the brain. Thymic atrophy results from apoptosis of immature double-positive T lymphocytes which might be caused indirectly by infection of a small proportion of thymus epithelial cells that express Bgp1a rather than by infection of T cells that do not express the receptor. Finally, polyclonal activation of B lymphocytes, leading to increased secretion of antibodies of the IgG2a isotype, involves a cascade of events, including cytokine secretion, that may result from the interaction of MHV-A59 with B cells and macrophages that express Bgp1a. Therefore, after viral infection, cellular expression of Bgp1a may have different results: cell lysis; alteration of cellular functions that may lead to indirect death of other cell types, or resistance to infection.
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PMID:Morphological analysis of mouse hepatitis virus A59-induced pathology with regard to viral receptor expression. 947 48

Mouse hepatitis virus receptor (MHVR) is a murine biliary glycoprotein (Bgp1(a)). Purified, soluble MHVR expressed from a recombinant vaccinia virus neutralized the infectivity of the A59 strain of mouse hepatitis virus (MHV-A59) in a concentration-dependent manner. Several anchored murine Bgps in addition to MHVR can also function as MHV-A59 receptors when expressed at high levels in nonmurine cells. To investigate the interactions of these alternative MHVR glycoproteins with MHV, we expressed and purified to apparent homogeneity the extracellular domains of several murine Bgps as soluble, six-histidine-tagged glycoproteins, using a baculovirus expression system. These include MHVR isoforms containing four or two extracellular domains and the corresponding Bgp1(b) glycoproteins from MHV-resistant SJL/J mice, as well as Bgp2 and truncation mutants of MHVR and Bgp1(b) comprised of the first two immunoglobulin-like domains. The soluble four-domain MHVR glycoprotein (sMHVR[1-4]) had fourfold more MHV-A59 neutralizing activity than the corresponding soluble Bgp1(b) (sBgp1(b)) glycoprotein and at least 1,000-fold more neutralizing activity than sBgp2. Although virus binds to the N-terminal domain (domain 1), soluble truncation mutants of MHVR and Bgp1(b) containing only domains 1 and 2 bound virus poorly and had 10- and 300-fold less MHV-A59 neutralizing activity than the corresponding four-domain glycoproteins. In contrast, the soluble MHVR glycoprotein containing domains 1 and 4 (sMHVR[1,4]) had as much neutralizing activity as the four-domain glycoprotein, sMHVR[1-4]. Thus, the virus neutralizing activity of MHVR domain 1 appears to be enhanced by domain 4. The sBgp1(b)[1-4] glycoprotein had 500-fold less neutralizing activity for MHV-JHM than for MHV-A59. Thus, MHV strains with differences in S-glycoprotein sequence, tissue tropism, and virulence can differ in the ability to utilize the various murine Bgps as receptors.
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PMID:Purified, soluble recombinant mouse hepatitis virus receptor, Bgp1(b), and Bgp2 murine coronavirus receptors differ in mouse hepatitis virus binding and neutralizing activities. 969 18

Mouse hepatitis virus strain A59 (MHV-A59) produces mild meningoencephalitis and severe hepatitis during acute infection. To determine whether an in vitro system could be established which would mimic in vivo replication of the virus, we examined the ability of MHV-A59 to replicate in primary cultures of hepatocytes derived from C57BL/6 mice. Infection of hepatocytes with MHV-A59 resulted in low levels of replication, with virus remaining cell associated. Maximum viral yield was observed at 24 hours postinfection, while occasional syncytia were observed at 48 hours postinfection. Primary glial cell culture represents a potential in vitro system representing the second main target of MHV-A59, namely the brain. It is known that MHV-A59 produces a productive, but nonlytic infection in these cultures. Since cell-to-cell fusion is associated with the cleavage of S, the observation of little or no syncytia following MHV-A59 infection of both hepatocytes and glial cells prompted us to examine the cleavage of the spike protein (S) by Western blot analysis. The cleavage of S is inefficient in MHV-A59 infected hepatocytes and in glial cells. Furthermore, no cleavage of this protein was detected in liver homogenates from C57BL/6 mice infected with MHV-A59. These data suggest that cleavage of the MHV-A59 S protein, and by inference cell-to-cell fusion, does not seem to be essential for entry and spread of the virus in vivo and in vitro.
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PMID:The mouse hepatitis virus A59 spike protein is not cleaved in primary hepatocyte and glial cell cultures. 978 25

Mouse hepatitis virus (MHV) A59 infection which causes acute encephalitis, hepatitis, and chronic demyelination, is one of the experimental models for multiple sclerosis. Previous studies showed that lethal infection of beta2-microglobulin 'knockout' (beta2M(-/-)) mice required 500-fold less virus and viral clearance was delayed as compared to infection of immunocompetent C57Bl/6 (B6) mice. To investigate the mechanism of the increased susceptibility of beta2M(-/-) mice to MHV-A59, we studied organ pathology and the distribution of viral antigen and RNA during acute and chronic infection. A59-infected beta2M(-/-) mice were more susceptible to acute encephalitis and hepatitis, but did not have increased susceptibility to demyelination. Viral antigen and RNA distribution in the brain was increased in microglia, lymphocytes, and small vessel endothelial cells while the distribution in neurons and glia was similar in beta2M(-/-) mice and B6 mice. Acute hepatitis and thymus cortical hypoplasia in beta2M(-/-) mice were delayed in onset but pathologic changes in these organs were similar to those in B6 mice. The low rate of demyelination in beta2M(-/-) mice was consistent with the low dose of the virus given. A less neurotropic virus MHV-2, caused increased parenchymal inflammation in beta2M(-/-) mice, but without demyelination. Thus, CD8+ cells were important for viral clearance from endothelial cells, microglia and inflammatory cells, but not from neuronal and glial cells. In addition, CD8+ cells played a role in preventing the spread of encephalitis.
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PMID:Cellular reservoirs for coronavirus infection of the brain in beta2-microglobulin knockout mice. 1002 35

Mouse hepatitis virus (MHV) provides an excellent animal model for the study of the immunopathological mechanisms involved in hepatic viral diseases. We previously generated an attenuated viral variant, YAC-MHV3, which induces a subclinical disease and recovery within 15 days. In contrast, the L2-MHV3 strain induces the development of a fulminant hepatitis, leading to death within 3 days. In this paper, we document intrahepatic and splenic T cell subpopulations involved in the hepatitis process and viral elimination identified in attenuated or pathogenic MHV3-infected C57BL/6 mice. Percentages of intrahepatic CD4(+) cells decreased in attenuated YAC-MHV3-infected mice, while they increased in mice infected with pathogenic L2-MHV3, compared with uninfected animals. Moreover, in YAC-MHV3-infected mice, the percentages of intrahepatic CD8(+) cells slightly decreased at 24 h pi, then increased until 15 days pi. In contrast, the CD4/CD8 ratios of splenic lymphoid subpopulations increased in the first days of infection and returned to normal values at 15 days pi. Intrahepatic NK1.1(+)alphabeta - TCR(inter) cells decreased in both virally infected groups of mice, while CD4(+)alphabeta - TCR(inter) LFA-1(high) cells increased in L2-MHV3-infected mice, in contrast with what was seen in YAC-MHV3-infected mice. However, these cells became anergic following Con A or PHA stimulation. Ex vivo studies showed that only the intrahepatic CD8(+) cells that were increased in YAC-MHV3-infected mice could be stimulated by lectins. In addition, in vitro viral infections revealed that L2-MHV3 viral infection led to an increase of intrahepatic CD4(+)alphabeta - TCR(inter) cells in the absence of CD8(+) cells only. These results indicate that the attenuated phenotype of the YAC-MHV3 virus is related to two different mechanisms: the first involves no increase of intrahepatic CD4(+)alphabeta - TCR(inter) or NK-T cells, while the second favors the recruitment and activation of CD8(+) cells in liver. The results are discussed in relation to the integrity of intrahepatic immune tolerance mechanisms and immune-mediated viral elimination.
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PMID:Recovery from mouse hepatitis virus infection depends on recruitment of CD8(+) cells rather than activation of intrahepatic CD4(+)alphabeta(-)TCR(inter) or NK-T cells. 1172 27

Dihydropyridine (DHP) type Ca2+ channel blocker (CCB) is effective in treatment of hepatitis in man. L-type Ca2+ channel is a target of DHP-CCB, and basic studies suggest that L-type Ca2+ channel alpha1D-subunit (Cav 1.3) seems to be a target of drug development for the treatment of hepatitis. Mouse hepatitis model is useful to study the effect of DHP-CCB on hepatitis. In order to use mouse hepatitis model to screen DHP-CCB specific for Cav 1.3, Cav 1.3 expressed in the mouse liver should have enough structural homology with that of human Cav 1.3. cDNA of the Cav 1.3 was cloned from mouse brain by reverse transcription polymerase chain reaction. The primary structure of the mouse Cav 1.3 comprises an open reading frame of 6540 bp encoding 2180 amino acids. Liver transcript lacked 60 and 45 bases from 1497 to 1556, and from 3949 to 3993 of the sequence, respectively, due to results of an alternative splicing. The present results indicated that mouse Cav 1.3 exhibited 96% homology with human Cav 1.3 and was expressed in the liver. Thus, mouse hepatitis model seemed to be useful to screen DHP-CCB specific for Cav 1.3.
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PMID:Cloning of the Cav 1.3 (alpha1D) L-type Ca2+ channel from mouse and its expression in the liver. 1501 Aug 58

Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of immunological disorders related to acute and chronic hepatitis. In this study, we have verified if the fulminant hepatitis induced by MHV3 could be related to an impairment of innate immunity. Groups of three C57BL/6 mice were infected with the pathogenic L2-MHV3 or attenuated YAC-MHV3 viruses, and the natural killer (NK) cell populations from liver, spleen and bone marrow were analysed. The percentage of intrahepatic NK1.1(+)T cell receptor (TCR)- cells did not increase while NK1.1(+)TCR(inter) cells decreased in both L2-MHV3- and YAC-MHV3-infected mice. Concurrently, splenic and myeloid NK1.1+ cells decreased in L2-MHV3-infected mice. However, the cytotoxic activity of NK cells increased in liver and decreased in bone marrow from pathogenic L2-MHV3-infected mice while no modification was detected in YAC-MHV3-infected mice. Flow cytometric analysis revealed that both normal and larger splenic or myeloid NK cells decreased more in pathogenic L2-MHV3-infected mice than in attenuated YAC-MHV3-infected mice. In vitro viral infections of interleukin (IL)-15-stimulated lymphoid cells from liver and bone marrow revealed that L2-MHV3 induced higher decreases in cell viability of NK1.1+ cells than the YAC-MHV3 variant. The NK cell decreases were due to the viral permissivity leading to cytopathic effects characterized by cell rounding, syncytia formation and apoptosis. Larger NK+ syncytia were observed in L2-MHV3-infected cells than in YAC-MHV3-infected cells. These results suggest that NK cell production is impaired by viral infection favouring fulminant hepatitis.
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PMID:Murine viral hepatitis involves NK cell depletion associated with virus-induced apoptosis. 1519 42

The use of individually ventilated caging (IVC) to house mice presents new challenges for effective microbiological monitoring. Methods that exploit the characteristics of IVC have been developed, but to the authors' knowledge, their efficacy has not been systematically investigated. Air exhausted from the IVC rack can be monitored, using sentinels housed in cages that receive rack exhaust air as their supply air, or using filters placed on the exhaust air port. To aid laboratory animal personnel in making informed decisions about effective methods for microbiological monitoring of mice in IVC, the efficacy of air monitoring methods was compared with that of contact and soiled bedding sentinel monitoring. Mice were infected with mouse hepatitis virus (MHV), mouse parvovirus (MPV), murine rotavirus (agent of epizootic diarrhea of mice [EDIM]), Sendai virus (SV), or Helicobacter spp. All agents were detected using contact sentinels. Mouse hepatitis virus was effectively detected in air and soiled bedding sentinels, and SV was detected in air sentinels only. Mouse parvovirus and Helicobacter spp. were transmitted in soiled bedding, but the efficacy of transfer was dependent on the frequency and dilution of soiled bedding transferred. Results were similar when the IVC rack was operated under positive or negative air pressure. Filters were more effective at detecting MHV and SV than they were at detecting MPV. Exposure of sentinels or filters to exhaust air was effective at detecting several infectious agents, and use of these methods could increase the efficacy of microbiological monitoring programs, especially if used with soiled bedding sentinels. In contemporary mouse colonies, a multi-faceted approach to microbiological monitoring is recommended.
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PMID:Efficacy of three microbiological monitoring methods in a ventilated cage rack. 1535 18

Murine hepatitis virus (MHV) infection provides a model system for the study of hepatitis, acute encephalitis, and chronic demyelinating disease. The spike glycoprotein, S, which mediates receptor binding and membrane fusion, plays a critical role in MHV pathogenesis. However, viral proteins other than S also contribute to pathogenicity. The JHM strain of MHV is highly neurovirulent and expresses a second spike glycoprotein, the hemagglutinin esterase (HE), which is not produced by MHV-A59, a hepatotropic but only mildly neurovirulent strain. To investigate a possible role for HE in MHV-induced neurovirulence, isogenic recombinant MHV-A59 viruses were generated that produced either (i) the wild-type protein, (ii) an enzymatically inactive HE protein, or (iii) no HE at all (A. Lissenberg, M. M. Vrolijk, A. L. W. van Vliet, M. A. Langereis, J. D. F. de Groot-Mijnes, P. J. M. Rottier, and R. J. de Groot, J. Virol. 79:15054-15063, 2005 [accompanying paper]). A second, mirror set of recombinant viruses was constructed in which, in addition, the MHV-A59 S gene had been replaced with that from MHV-JHM. The expression of HE in combination with A59 S did not affect the tropism, pathogenicity, or spread of the virus in vivo. However, in combination with JHM S, the expression of HE, regardless of whether it retained esterase activity or not, resulted in increased viral spread within the central nervous system and in increased neurovirulence. Our findings suggest that the properties of S receptor utilization and/or fusogenicity mainly determine organ and host cell tropism but that HE enhances the efficiency of infection and promotes viral dissemination, at least in some tissues, presumably by serving as a second receptor-binding protein.
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PMID:Expression of hemagglutinin esterase protein from recombinant mouse hepatitis virus enhances neurovirulence. 1630 77

Mouse hepatitis virus strain JHM (MHV-JHM) causes acute encephalitis and acute and chronic demyelinating diseases in mice. Dendritic cells (DCs) are key cells in the initiation of innate and adaptive immune responses, and infection of these cells could potentially contribute to a dysregulated immune response; consistent with this, recent results suggest that DCs are readily infected by another strain of mouse hepatitis virus, the A59 strain (MHV-A59). Herein, we show that the JHM strain also productively infected DCs. Moreover, mature DCs were at least 10 times more susceptible than immature DCs to infection with MHV-JHM. DC function was impaired after MHV-JHM infection, resulting in decreased stimulation of CD8 T cells in vitro. Preferential infection of mature DCs was not due to differential expression of the MHV-JHM receptor CEACAM-1a on mature or immature cells or to differences in apoptosis. Although we could not detect infected DCs in vivo, both CD8(+) and CD11b(+) splenic DCs were susceptible to infection with MHV-JHM directly ex vivo. This preferential infection of mature DCs may inhibit the development of an efficient immune response to the virus.
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PMID:Preferential infection of mature dendritic cells by mouse hepatitis virus strain JHM. 1647 57


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