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)

The cellular receptor for the murine coronavirus mouse hepatitis virus (MHV) has been identified as a member of the murine carcinoembryonic antigen (CEA) family (R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). However, the receptor protein was not detected in some of the susceptible mouse tissues. We therefore examined whether other types of MHV receptor might exist. By polymerase chain reaction with the conserved sequences of murine CEA gene family members (mmCGM) as primers, we detected two CEA-encoding RNAs in the mouse liver. One of them (1.3 kb) encodes mmCGM1, which has previously been identified as the receptor for MHV, and the other one (0.8 kb) was shown to encode another member of mouse CGM, mmCGM2. The sequence analysis showed that mmCGM2 lacks 564 nucleotides in the middle of the gene compared with mmCGM1. These two CEA transcripts are probably derived from the same gene by an alternative splicing mechanism. Expression of either of these cDNA clones in COS-7 cells rendered these cells susceptible to MHV infection, suggesting that not only mmCGM1 but also mmCGM2 serves as a receptor for MHV. The mmCGM2 was the major CEA species in the mouse brain, which is a main target organ for the neurotropic strains of MHV. Very little mmCGM1 was detected in the mouse brain or in cells of the susceptible mouse astrocytoma cell line DBT. This result indicates that MHV may utilize different CEA molecules as the major receptor in the mouse brain and in the liver. This is a first identification of multiple receptors for a single virus. The presence of different receptors in different tissues may explain the target cell specificity of certain MHVs.
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PMID:Mouse hepatitis virus utilizes two carcinoembryonic antigens as alternative receptors. 132 65

Twelve clones derived from the cells persistently infected with the JHM strain (JHMV) of mouse hepatitis virus (MHV) were established from mouse astrocytoma-derived DBT cells and characterized. All the cell clones were resistant to superinfection with MHV. Only one of the persistently infected cell clone synthesized viral RNA and proteins and produced virus particles. Viral RNA was detectable in some other cell clones without production of viral protein nor the virus. No cell clones exhibited contact fusion activity. The results suggested that such variety of cell clones might have resulted from persistent infection with JHMV.
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PMID:Characterization of DBT cell clones derived from cells persistently infected with the JHM strain of mouse hepatitis virus. 859 85

Persistent infection of murine astrocytoma (DBT) cells with mouse hepatitis virus (MHV) has been established. From this in vitro virus-host system, persistence is mediated at the level of cellular MHV receptor (MHVR) expression and increased virus virulence. MHV persistence selects for resistant host cell populations which abate virus replication. Reductions in MHVR expression were significantly associated with increased host resistance, and transfection of MHVR into resistant host cells completely restored the capacity of cells to support efficient replication of MHV strain A59. The emergence of resistant host cells coselected for variant viruses that had increased avidity for MHVR and also recognized different receptors for entry into resistant cells. These data illustrate that MHV persistence in vitro provides a model to identify critical sites of virus-host interaction at the cellular level which are altered during the evolution of host cell resistance to viral infection and the coevolution of virus virulence.
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PMID:Molecular anatomy of mouse hepatitis virus persistence: coevolution of increased host cell resistance and virus virulence. 864 32

Molecular mechanisms regulating virus xenotropism and cross-species transmission are poorly understood. Host range mutants (MHV-H2) of mouse hepatitis virus (MHV) strains were isolated from mixed cultures containing progressively increasing concentrations of nonpermissive Syrian baby hamster kidney (BHK) cells and decreasing concentrations of permissive murine astrocytoma (DBT) cells. MHV-H2 was polytrophic, replicating efficiently in normally nonpermissive BHK cells, Syrian and Chinese hamster (DDT-1 and CHO) cells, human adenocarcinoma (HRT), primate kidney (VERO) and in murine 17Cl-1 cell lines. Little if any virus replication was detected in feline kidney (CRFK), and porcine testicular (ST) cell lines. To study the effects of xenotrophic spread on virus receptor-interactions in the original host, murine DBT cells were pretreated with a monoclonal antibody (MAb) CC1, directed against the MHV receptor, MHVR, a biliary glycoprotein (Bgp1a). Under treatment conditions that completely ablated the replication of the parental MHV strains, CC1 antireceptor antibodies did not block MHV-H2 replication. Following expression of MHVR in normally nonpermissive ST and CRFK cells, infection with the parental MHV strains, but not MHV-H2 was observed. To characterize the molecular basis preventing the interaction between MHV-H2 and MHVR, revertants of MHV-H2 (MHV-H2R6, MHV-H2R11) were isolated following a persistent MHV-H2 infection in DBT cells. These revertant viruses efficiently recognized MHVR, however infection of murine cells was resistant to MAb CC1 blockade. In addition, MHV-H2 and the revertant viruses efficiently recognized other Bgp receptors for docking and entry. These data suggest that interspecies transfer may remodel normal virus-receptor interactions that may result in altered virulence, tropism or pathogenesis in the original host.
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PMID:Virus-receptor interactions and interspecies transfer of a mouse hepatitis virus. 978 62

The genomic alterations in preneoplastic lesions are summarized in this review. 3p and 9p in the lung, 9p in the bladder, 8p in the prostata, 19q and 1p in oligodendroglioma, and 22q in meningioma were reported to be deleted. Somatic mutation of p53 was found in preneoplastic lesions of the esophagus, stomach, colon, thyroid, and astrocytoma. Adenoma-carcinoma sequence (Apc, ras, p53 gene alterations) in colon, LKB1 gene in Peutz-Jeghers syndrome, Smad4 in juvenile polyposis, hMSH2, hMLH1, PMS1, PMS2 genes in HNPCC, VHL gene in kidney, WT1 in Wilms tumor, RB gene in retinoblastoma, and ret gene in MEN were reportedly altered in preneoplastic lesions involved in hereditary tumors. Cervical dysplasia and papilloma of the head and neck infected by human papilloma virus and liver infected by B-type hepatitis virus are also precancerous. Genomic instability, APC gene alteration, point mutation of K-ras in preneoplastic lesions of stomach and K-ras and p16 alterations in metaplasia of pancreas were also found. Advances in research on genomic alterations in preneoplastic lesions will contribute to prevention and early detection of cancer.
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PMID:[Genomic alterations in preneoplastic lesions]. 1250 66

We observed that the nonfusogenic mouse hepatitis virus (MHV) strain MHV-2 reached a titer of approximately 2 log10 higher than that of the fusogenic strain A59 in astrocytoma DBT cells. To determine whether the spike protein is responsible for the difference, a recombinant virus, Penn-98-1, that contains the A59 genome with a spike from MHV-2 was used to infect DBT cells. Results showed that Penn-98-1 behaved like MHV-2, thus establishing a role for the spike protein in viral growth. The inverse correlation between viral fusogenicity and growth was further established in four different cell types and with a fusogenic mutant, the S757R mutant, derived from isogenic Penn-98-1. While both A59 and Penn-98-1 entered cells at similar levels, viral RNA and protein syntheses were significantly delayed for A59. Interestingly, when the genomic RNAs were delivered directly into the cells via transfection, the levels of gene expression for these viruses were similar. Furthermore, cell fractionation experiments revealed that significantly more genomic RNAs for the nonfusogenic MHVs were detected in the endoplasmic reticulum (ER) within the first 2 h after infection than for the fusogenic MHVs. Pretreatment of Penn-98-1 with trypsin reversed its properties in syncytium formation, virus production, and genome transport to the ER. These findings identified a novel role for the spike protein in regulating the uncoating and delivery of the viral genome to the ER after internalization.
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PMID:The spike protein of murine coronavirus regulates viral genome transport from the cell surface to the endoplasmic reticulum during infection. 1957 Aug 58