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)

We have previously shown that some strains of the murine coronavirus mouse hepatitis virus (MHV) synthesize an additional mRNA species (mRNA 2b, previously called mRNA 2a) with a size intermediate between that of mRNAs 2 and 3, suggesting the presence of an optional transcriptional initiation site. This transcriptional start is dependent on the leader sequence of the virus strains. To study the mechanism of coronavirus transcriptional regulation, we have cloned and sequenced the region of the viral genome corresponding to the 5' unique coding region of mRNA 2 of the JHM strain of MHV. In addition to the open reading frame (ORF) predicted to encode the viral nonstructural protein p30, a second complete ORF, with the potential to encode a 439-amino-acid polypeptide, was discovered. The transcriptional initiation sites of both mRNA 2a (formerly called mRNA 2) and mRNA 2b were determined by primer extension studies and RNA sequencing. The data indicated that transcription of mRNA 2a initiated at a site, UCUAUAC, that resembled the consensus intergenic sequence. In contrast, the start signal of the optional mRNA 2b, UAAUAAAC, deviated from the consensus sequence. mRNA 2b is a functional mRNA, as shown by in vitro translation studies of mRNA and ORF 2b and by the detection of an additional viral structural protein, gp65, in the JHM strain that synthesized this mRNA. Although the A59 strain of MHV was found to retain ORF 2b, it lacked the correct transcriptional and translational start signals for this gene. This study has therefore identified an optional gene product for murine coronaviruses and provided insights into the mechanism of regulation of MHV RNA transcription.
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PMID:Identification of a new transcriptional initiation site and the corresponding functional gene 2b in the murine coronavirus RNA genome. 254 94

The expression of mouse hepatitis virus (MHV) E2-specific mRNA, the E2 polypeptide and its associated cell fusing activity was monitored in various cell types inoculated with a recombinant vaccinia virus, designated vMS containing the E2 gene. The results suggest that host cell permissiveness to MHV infection correlates with cellular susceptibility to membrane fusion mediated by the MHV E2 glycoprotein. In addition, we utilized a genetic approach to the analysis of host cell functions involved in determining permissiveness to MHV. By using the chemical mutagen ethyl methanesulphonate, mouse fibroblast cell mutants were generated and selected for their resistance to cell killing by MHV. When challenged with MHV, all five mutants examined gave rise to persistent infections, in contrast to wild-type L-2 cells which were rapidly killed by the virus. The results provide genetic evidence in support of a previous correlation proposed between MHV permissiveness and two host determinants, namely susceptibility to MHV infection and to MHV-mediated cell fusion. Fusion resistance was specific to fusion mediated by the MHV E2 glycoprotein as shown in contact fusion assays between uninfected cells and cells infected either with MHV or with an E2-expressing recombinant vaccinia virus. In contrast, mutant cells were not resistant to fusion after treatment with polyethylene glycol. The observed high rate of generation of these mutants suggests that the conversion of a fully MHV-susceptible cell to a semi-resistant one is a fairly common event, possibly involving a single mutation. In this case, resistance to MHV infection and to E2-mediated membrane fusion may depend on a common host function. This result provides prospects for the precise genetic and biochemical characterization of the steps involved in host cell permissiveness to MHV infection.
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PMID:Mutation of host cell determinants which discriminate between lytic and persistent mouse hepatitis virus infection results in a fusion-resistant phenotype. 255 60

The LEC (Long-Evans with a cinnamon-like coat color) rat is a new mutant strain with hereditary hepatitis. The rate of DNA synthesis, the relative amounts of binucleated cells, and the polyploidizations of LEC hepatocytes have been analyzed. Markedly high polyploidy, such as 32n and 64n, were detected after manifestation of hepatitis; however, no aneuploidy was detected. Bi-, tri- and tetranucleated cells whose nuclei occasionally differed in size were observed after the manifestation of hepatitis. In addition to small hepatocytes and oval cells in the periportal area of the hepatic lobule, enlarged cells with huge nuclei were also labeled with BrdU, indicating that in LEC rats suffering from hepatitis abnormal mitosis may be relevant to high polyploidization and multinucleation. Polypeptide analysis using 2D-PAGE detected the apparent lack of expression of two polypeptides, p29.5 and p30, in LEC liver cells; however, linkage analysis indicated no correlation between these peptide defects and the manifestation of hepatitis.
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PMID:Hereditary hepatitis in LEC rats: accumulation of abnormally high ploid nuclei. 262 Mar 8

Sera from 23 children with autoimmune chronic active hepatitis and positive for anti-liver-kidney-microsome antibody (LKMA), as defined by immunofluorescence, were analysed by Western blot (WB) and two-dimensional gel electrophoresis using rat liver microsomes as antigen, and by WB and dot-blot analysis with rat liver microsomal subfractions. Western blot analysis showed three patterns of reactivity: 13 sera recognized a 50 kD polypeptide, six sera a 66 kD polypeptide and four sera both of them. Two-dimensional gel electrophoresis, WB, and dot-blot analysis showed the 66 kD antigen to have a pI of 5.4 and to be located in the smooth domain of the endoplasmic reticulum. Western blot analysis using monospecific antisera against human IgG subclasses showed the LKMA directed against the 66 kD antigen to be mainly of the IgG1 subclass. These results indicate that LKMA associated with a subgroup of autoimmune hepatitis of children react with at least two different microsomal antigens in rat liver: (1) the 50 kD polypeptide, recently shown to be a cytochrome P-450 of the IID subfamily, and (2) a new antigen of 66 kD, the location of which suggests it may also be part of the mono-oxygenase complex.
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PMID:A new antigen recognized by anti-liver-kidney-microsome antibody (LKMA). 270 79

Previous studies have demonstrated that patients with halothane-induced hepatitis have serum antibodies that are directed against novel liver microsomal neoantigens and have suggested that these neoantigens may play an immunopathological role in development of the patients' liver damage. These investigations have further revealed that the antibodies are directed against distinct polypeptide fractions (100 kDa, 76 kDa, 59 kDa, 57 kDa, 54 kDa) that have been covalently modified by the reactive trifluoroacetyl halide metabolite of halothane. In this paper, the trifluoroacetylated (TFA) 59-kDa neoantigen (59-kDa-TFA) recognized by the patients' antibodies was isolated from liver microsomes of halothane-treated rats by chromatography on an immunoaffinity column of anti-TFA IgG. Antibodies were raised against the 59-kDa-TFA protein and were used to purify the native protein from liver microsomes of untreated rats. Based upon its apparent monomeric molecular mass, NH2-terminal amino acid sequence, catalytic activity, and other physical properties, the protein has been identified as a previously characterized microsomal carboxylesterase (EC 3.1.1.1). A similar strategy may be used to purify and characterized neoantigens associated with other drug toxicities that are believed to have an immunopathological basis.
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PMID:Human anti-endoplasmic reticulum antibodies in sera of patients with halothane-induced hepatitis are directed against a trifluoroacetylated carboxylesterase. 291 77

cDNAs prepared from viral genomic RNA purified from two strains of infectious bronchitis virus (IBV) (Beaudette and M41) have been cloned into pBR322. Three of these clones, which contain the complete sequences of mRNA A for both strains, except for the leader sequences which are only present on the subgenomic messenger RNAs, have been sequenced using the dideoxy method. The sequences are similar for both strains, each containing a single long open reading frame of 1227 bases which predicts a polypeptide of molecular weight approximately 45 000. The genome position and size of this predicted polypeptide are consistent with it being the gene for the nucleocapsid protein. The amino acid sequence shows considerable homology with those of the nucleocapsids of murine hepatitis virus strains A59 and JHM. The major difference between the sequences determined for the two IBV strains is that the 3' non-coding region of the Beaudette strain contains a 184 base segment which is not present in the M41 strain.
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PMID:Sequences of the nucleocapsid genes from two strains of avian infectious bronchitis virus. 298 1

Today we distinguish 4 forms of viral hepatitis: hepatitis A, hepatitis B, hepatitis non-A, non-B and hepatitis occurring in the course of other viral diseases. The viruses of hepatitis A and hepatitis B have been identified but the agent(s) of hepatitis non-A, non-B remain unknown. Inoculation of normal pooled human immunoglobulin provides passive immunity for 2-3 months against hepatitis A but not against hepatitis B or hepatitis non-A, non-B. For passive protection against hepatitis B a special immunoglobulin with a high anti-HBs titer must be used whereas the protection against hepatitis non-A, non-B with immunoglobulin is uncertain. Live attenuated and noninfectious polypeptide vaccines for active immunisation against hepatitis A are currently developed and first clinical trials have begun with the live attenuated vaccine. A vaccine consisting of noninfectious highly purified HBsAg derived from the plasma of HBV carriers is in general use since two years and has proved safe and highly effective and vaccines are now developed from HBsAg obtained through molecular cloning of the HBsAg genome in plasmids and expression of the genome with HBsAg production in yeast cells. First clinical studies with this vaccine are encouraging and these as well as purely synthetic vaccines will in time replace the currently used vaccines. No vaccines could be developed so far against hepatitis non-A, non-B because the agent(s) of this disease are unknown.
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PMID:[Viral hepatitis and immunoprophylaxis]. 298 80

The structure of the envelope protein E1 of two coronaviruses, mouse hepatitis virus strain A59 and infectious bronchitis virus, was analyzed by applying several theoretical methods to their amino acid sequence. The results of these analyses combined with earlier data on the orientation and protease sensitivity of E1 assembled in microsomal membranes lead to a topological model. According to this model, the protein is anchored in the lipid bilayer by three successive membrane-spanning helices present in its N-terminal half whereas the C-terminal part is thought to be associated with the membrane surface; these interactions with the membrane protect almost the complete polypeptide against protease digestion. In addition, it is predicted that the insertion of E1 into the membrane occurs by the recognition of the internal transmembrane region(s) as a signal sequence.
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PMID:Predicted membrane topology of the coronavirus protein E1. 300 26

The first event after infection with mouse hepatitis virus strain A59 (MHV-A59) is presumed to be the synthesis of an RNA-dependent RNA polymerase from the input genomic RNA. The synthesis and processing of this putative polymerase protein was studied in a cell-free translation system utilizing 60S RNA from MHV-A59 virions. The polypeptide products of this reaction included two major species of 220 and 28 kilodaltons. Kinetics experiments indicated that both p220 and p28 appeared after 60 min of incubation and that protein p28 was synthesized initially as the N-terminal portion of a larger precursor protein. When the cell-free translation products were labeled with N-formyl[35S]methionyl-tRNAi, p28 was the predominant radioactive product, confirming its N-terminal location within a precursor protein. Translation in the presence of the protease inhibitors leupeptin and ZnCl2 resulted in the disappearance of p28 and p220 and the appearance of a new protein, p250. This product, which approached the maximal size predicted for a protein synthesized from genomic RNA, was not routinely detected in the absence of inhibitors even under conditions which optimized the translation reaction for elongation of proteins. Subsequent chelation of ZnCl2 resulted in the partial cleavage of the precursor protein and the reappearance of p28. One-dimensional peptide mapping with Staphylococcus aureus V-8 protease confirmed the precursor-product relationship of p250 and p28. The results show that MHV virion RNA, like many other viral RNAs, is translated into a large polyprotein, which is cleaved soon after synthesis into smaller, presumably functional proteins. This is in marked contrast to the synthesis of other MHV proteins, in which minimal proteolytic processing occurs.
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PMID:Translation and processing of mouse hepatitis virus virion RNA in a cell-free system. 301 79

Sequences encoding the surface projection glycoprotein of the coronavirus, murine hepatitis virus (MHV), strain JHM, have been cloned into pAT153 using cDNA produced by priming with specific oligonucleotides on infected cell RNA. The regions of three clones pJMS1010, pJS112 and pJS92, which together encompass the surface protein gene have been sequenced by the chain termination method. The sequence of the primary translation product, deduced from the DNA sequence, predicts a polypeptide of 1,235 amino acids with a molecular weight of 136,600. This polypeptide displays the features characteristic of a group 1 membrane protein; an amino-terminal signal sequence and carboxy-terminal membrane and cytoplasmic domains. There are 21 potential glycosylation sites in the polypeptide and a cysteine-rich region in the vicinity of the transmembrane domain. During maturation proteolytic processing of the polypeptide occurs and at positions 624 to 628 the sequence Arg-Arg-Ala-Arg-Arg is found, which is similar to a number of basic sequences involved in the cleavage of enveloped RNA virus glycoproteins. The fusogenic properties of the MHV surface protein do not appear to correlate with a strongly hydrophobic region at the putative amino terminus of the carboxy-terminal cleavage product.
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PMID:Nucleotide sequence of the gene encoding the surface projection glycoprotein of coronavirus MHV-JHM. 302 48


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