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 receptors for a coronavirus, mouse hepatitis virus (MHV), have been recently identified as one or more members of the carcinoembryonic antigen (CEA) family. The neurotropic JHM strain of MHV (MHV-JHM) possesses a highly fusogenic surface (S) glycoprotein. This protein is now shown to promote the spread of MHV into cells lacking the specific CEA-related MHV receptor. Resistant cells are recruited into MHV-induced syncytium with consequent production of progeny virus. Cell-to-cell spread of virus via membrane fusion without the requirement for specific cell surface receptor offers a novel way for virus to spread within infected hosts.
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PMID:Cell receptor-independent infection by a neurotropic murine coronavirus. 141 26

It has previously been shown that the M (E1) glycoprotein of mouse hepatitis virus strain A59 (MHV-A59) contains only O-linked oligosaccharides and localizes to the Golgi region when expressed independently. A detailed pulse-chase analysis was made of the addition of O-linked sugars to the M protein; upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, three different electrophoretic forms could be distinguished that corresponded to the sequential acquisition of N-acetylgalactosamine (GalNAc), galactose (Gal), and sialic acid (SA). A fourth and fifth form could also be detected which we were unable to identify. Following Brefeldin A treatment, the M protein still acquired GalNAc, Gal, and SA, but the fourth and fifth forms were absent, suggesting that these modifications occur in the trans-Golgi network (TGN). In contrast, in the presence of BFA, the G protein of vesicular stomatitis virus (VSV), which contains N-linked oligosaccharides, acquired Gal and fucose but not SA. These results are consistent with earlier published data showing that Golgi compartments proximal to the TGN, but not the TGN itself, relocate to the endoplasmatic reticulum/intermediate compartment. More importantly, our data argue that, whereas addition of SA to N-linked sugars occurs in the TGN the acquisition of both SA on O-linked sugars and the addition of fucose to N-linked oligosaccharides must occur in Golgi compartments proximal to the TGN. The glycosylation of the M protein moreover indicates that it is transported to trans-Golgi and TGN. This was confirmed by electron microscopy immunocytochemistry, showing that the protein is targeted to cisternae on the trans side of the Golgi and co-localizes, at least in part, with TGN 38, a marker of the TGN, as well as with a lectin specific for sialic acid.
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PMID:O-glycosylation of the coronavirus M protein. Differential localization of sialyltransferases in N- and O-linked glycosylation. 162 9

The receptor for mouse hepatitis virus (MHV), a murine coronavirus, is a 110- to 120-kDa glycoprotein on intestinal brush border membranes and hepatocyte membranes. The N-terminal 25-amino acid sequence of immunoaffinity-purified MHV receptor was identical to the predicted mature N termini of two mouse genes related to human carcinoembryonic antigen (CEA) and was strongly homologous to the N termini of members of the CEA family in humans and rats. Polyclonal antibodies to human CEA recognized the immunoaffinity-purified MHV receptor and the MHV receptor in liver membranes and intestinal brush border membranes from MHV-susceptible mouse strains. In membranes from MHV-resistant SJL/J mice, the anti-CEA antibodies recognized a homologous glycoprotein that failed to bind MHV. The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo. The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution. Thus, the MHV receptor is, to our knowledge, the first member of the CEA family of glycoproteins to be identified as a virus receptor.
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PMID:Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins. 164 19

Rabbit polyclonal antiidiotypic antibodies were generated against a neutralizing mAb specific for a conformational epitope on the S glycoprotein of murine hepatitis virus, strain A59 (MHV-A59). These anti-Id were directed predominantly against an Id that was undetectable in rabbit and rat anti-MHV-A59 sera and weakly represented in syngeneic and allogeneic antiviral sera. However, some partial idiotypic sharing was observed between the Id-bearing antibody and a mAb with a similar antigenic site specificity. The anti-Id inhibited the virus-binding and neutralizing activities of the immunizing antibody, demonstrating that they recognize paratope-associated idiotopes. Mice immunized with affinity-purified anti-Id developed MHV-A59-specific antibodies that neutralized viral infectivity to high titers. Moreover, these animals survived an otherwise lethal challenge with viral murine hepatitis virus, unlike control mice immunized with normal rabbit Ig. These results indicate that at least a subpopulation of the polyclonal anti-Id could induce a protective immune response directed toward a biologically important MHV-A59 epitope, and demonstrate the feasibility of antiidiotypic vaccination against a coronavirus infection.
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PMID:Antiidiotypic vaccination against murine coronavirus infection. 166 13

Neuroattenuated variants of mouse hepatitis virus type 4 (MHV-4) selected for resistance to neutralizing monoclonal antibodies (R.G. Dalziel, P.W. Lampert, P. J. Talbot, and M. J. Buchmeier, J. Virol. 59:463-471, 1986) were found to harbor large deletions in both mRNA 3 and its protein product, the 180-kilodalton viron spike (S) glycoprotein. By using antipeptide antibodies directed against selected portions of the chain, deletions were mapped to the middle of the amino-terminal S1 fragment, one of the two posttranslational cleavage products of S, and involved omission of 15 kilodaltons of protein. Deletion mutants could be selected only after multiple passage of virus through cultured cell lines; minimally passaged MHV-4 stocks contained putative point mutants selectable by neutralizing monoclonal antibodies but no deletions. Enhanced growth of deletion mutants relative to wild-type virus was observed in four cell lines used for virus propagation and was attributed to delayed and diminished cytopathic effects that allowed cultures to support virus production for prolonged periods. This hypothesis was reinforced by the finding that no selective advantage for the deletion mutants was observed in two cell lines resistant to virus-induced cytopathic effects. These results indicate that the passaging of MHV-4 in culture generates heterogeneity in S structure and eventually selects for rare neutralization-resistant deletion mutants with decreased virulence properties.
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PMID:Neutralization-resistant variants of a neurotropic coronavirus are generated by deletions within the amino-terminal half of the spike glycoprotein. 168 27

Monoclonal antibodies (MAbs) directed against the E2 glycoprotein of mouse hepatitis virus (MHV) have been classified according to their ability to bind to either of the two purified 90,000-molecular-weight subunits (90K subunits) of the 180K peplomeric glycoprotein E2. Correlation with previously reported information about these MAbs suggest that both of the subunits of E2 are important for viral infectivity and cell fusion. Incubation of trypsin-treated virions at pH 8.0 and 37 degrees C released only the E2N subunit from virions. The pattern of MAb reactions suggested that a conformational change occurred in the E2N subunit in association with its release from virions under mildly alkaline conditions at 37 degrees C, the same conditions which are optimal for coronavirus-induced cell fusion.
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PMID:Monoclonal antibodies to the peplomer glycoprotein of coronavirus mouse hepatitis virus identify two subunits and detect a conformational change in the subunit released under mild alkaline conditions. 169 50

A panel of murine hepatitis virus (MHV) surface (S) glycoprotein-specific monoclonal antibodies (MAbs), which recognize either continuous or discontinuous epitopes, were tested in competitive binding assays. The results indicate that the binding site of MAb 30B amino acids 395 to 406 in the amino-terminal S1 subunit, is involved in the discontinuous epitope designated antigenic site A. This site is a major determinant for the induction of neutralizing antibodies. These data define, for the first time, the location of a functionally important domain on the MHV S protein.
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PMID:Localization of antigenic sites on the surface glycoprotein of mouse hepatitis virus. 171 62

Numerous studies have provided indirect evidence that the spike glycoprotein of coronaviruses (E2 or S) bears determinants for pathogenesis and the induction of protective immunity. In order to directly evaluate its immunogenicity, the E2 glycoprotein of the murine hepatitis virus, strain A59, was purified by immunoaffinity chromatography. High titers of neutralizing and fusion inhibiting antibodies were induced in mice vaccinated with purified E2/S in Freund's adjuvant, which were protected from an intracerebral challenge with 10 LD50 of MHV-A59. This study provides a direct demonstration of the importance of the coronavirus spike glycoprotein in the induction of a protective immune response.
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PMID:Protection of mice from lethal coronavirus MHV-A59 infection by monoclonal affinity-purified spike glycoprotein. 171 62

The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated a cDNA clone (MHVR1) encoding the MHV receptor. The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail, MHVR1 is closely related to the murine CEA-related clone mmCGM1 (Mus musculus carcinoembryonic antigen gene family member). Western blot (immunoblot) analysis performed with antireceptor antibodies detected a glycoprotein of 120 kDa in BHK cells stably transfected with MHVR1. This corresponds to the size of the MHV receptor expressed in mouse intestine and liver. Human and hamster fibroblasts transfected with MHVR1 became susceptible to infection with MHV-A59. Like MHV-susceptible mouse fibroblasts, the MHVR1-transfected human and hamster cells were protected from MHV infection by pretreatment with monoclonal antireceptor antibody CC1. Thus, the 110- to 120-kDa CEA-related glycoprotein encoded by MHVR1 is a functional receptor for murine coronavirus MHV-A59.
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PMID:Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV. 171 35

Infection of susceptible murine cells with the coronavirus mouse hepatitis virus type 4 (MHV4) results in extensive cell-cell fusion at pHs from 5.5 to 8.5. The endosomotropic weak bases chloroquine and ammonium chloride do not prevent MHV4 infection. In marked contrast, we have selected variants from a neural cell line persistently infected with MHV4 which are entirely dependent on acid pH to fuse host cells and are strongly inhibited by endosomotropic weak bases. Wild-type and variant viruses were compared at the level of the fusion-active surface (S) glycoprotein gene. Cloning and sequencing of each 4,131-base open reading frame predicted a total of eight amino acid differences which fell into three distinct clusters. Each S glycoprotein, when expressed from cDNA, was synthesized in equivalent amounts, and similar proportions were transported to the cell surface. Wild-type S induced cell-cell fusion at neutral pH, whereas variant S required prolonged exposure to acidic pH to induce fusion. Expression of hybrid S genes prepared by exchange of restriction fragments between wild-type and variant cDNAs revealed that elimination of neutral pH fusion was solely dependent on amino acid alterations at positions 1067 (Q to H), 1094 (Q to H), and 1114 (L to R). These changes lie within a predicted heptad repeat region of the transmembrane cleavage fragment of S (S2). These findings demonstrate that the pH dependence of coronavirus fusion is highly variable and that this variability can be determined by as few as three amino acid residues.
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PMID:Alteration of the pH dependence of coronavirus-induced cell fusion: effect of mutations in the spike glycoprotein. 184 11


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