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 defective interfering (DI) RNA MIDI of mouse hepatitis virus strain A59 (MHV-A59) contains a large open reading frame (ORF) spanning almost its entire genome. This ORF consists of sequences derived from ORF1a, ORF1b, and the nucleocapsid gene. We have previously demonstrated that mutations that disrupt the ORF decrease the fitness of MIDI and its derivatives (R. J. de Groot, R. G. van der Most, and W. J. M. Spaan, J. Virol. 66:5898-5905, 1992). To determine whether translation of the ORF per se is required or whether the encoded polypeptide or a specific sequence is involved, we analyzed sets of related DI RNAs containing different ORFs. After partial deletion of ORF1b and nucleocapsid gene sequences, disruption of the remaining ORF is still lethal; translation of the entire ORF is not essential, however. When a large fragment of the MHV-A59 spike gene, which is not present in any of the MHV-A59 DI RNAs identified so far, was inserted in-frame into a MIDI derivative, translation across this sequence was vital to DI RNA survival. Thus, the translated sequence is irrelevant, indicating that translation per se plays a crucial role in DI virus propagation. Next, it was examined during which step of the viral life cycle translation plays its role. Since the requirement for translation also exists in DI RNA-transfected and MHV-infected cells, it follows that either the synthesis or degradation of DI RNAs is affected by translation.
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PMID:Translation but not the encoded sequence is essential for the efficient propagation of the defective interfering RNAs of the coronavirus mouse hepatitis virus. 774 22

C/EBP is a sequence-specific DNA-binding protein. In order to identify its distribution and localization, immunohistochemical technique (ABC method) was done using anti-C/EBP polypeptide antibodies 1103#, 425# in liver specimens from 20 normal adults, 5 neonates, 6 patients with hepatitis, 25 with liver cirrhosis, 80 with hepatocellular carcinoma (40 cases were associated with surrounding nontumorous tissues) and 26 patients with cholangiocarcinoma (15 cases were associated with surrounding nontumorous tissues). The results showed that C/EBP was diffusely distributed in nuclei and cytoplasm of differentiated liver cells and very low or undetectable in liver cancer cells. The manifestation of C/EBP correlated with degree of differentiation of tumour cells, and was obviously weaker than that in surrounding nontumorous tissues. C/EBP positive staining has also been found in regenerating epithelial cells of bile ductules. The results suggested that C/EBP should play an important role in establishing and maintaining the differentiation of liver cells.
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PMID:Immunohistochemical demonstration of CCAAT/enhancer binding protein (C/EBP) in human liver tissues of various origin. 780 44

Mouse hepatitis virus strain A59 encodes a papain-like cysteine proteinase (PLP-1) that, during translation of ORF1a, cleaves p28 from the amino terminus of the growing polypeptide chain. In order to determine the amino acid sequences surrounding the p28 cleavage site, the first 4.6 kb of murine hepatitis virus strain A59 ORF1a was expressed in a cell-free transcription-translation system. Amino-terminal radiosequencing of the resulting downstream cleavage product demonstrated that cleavage occurs between Gly-247 and Val-248. Site-directed mutagenesis of amino acids surrounding the p28 cleavage site revealed that substitutions of Arg-246 (P2) and Gly-247 (P1) nearly eliminated cleavage of p28. Single-amino-acid substitutions of other residues between P7 and P2' were generally permissive for cleavage, although a few changes did greatly reduce proteolysis. The relationship between the p28 cleavage site and other viral and cellular papain proteinase cleavage sites is discussed.
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PMID:Identification of the murine coronavirus p28 cleavage site. 781 47

Highly purified radiolabeled mouse hepatitis virus (MHV) A59 contained a previously overlooked protein which coelectrophoreses with the gene 5b product immunoprecipitated from infected cells. The gene 5b protein is post-translationally acylated. Rabbit antibody raised against a recombinant gene 5b protein expressed in Escherichia coli neutralized viral infectivity in the presence of complement, although not in the absence of complement. Immunofluorescent staining of MHV-infected cells with two anti-peptide antibodies revealed that the gene 5b product is membrane-associated and is transported to the cell surface, findings consistent with the prediction of a membrane-spanning segment in the gene 5b polypeptide. These results suggest strongly that the gene 5b polypeptide represents a new MHV virion envelope protein which is homologous to the TGEV ORF 4 and IBV 3c proteins.
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PMID:Mouse hepatitis virus gene 5b protein is a new virion envelope protein. 803 Feb 2

C/EBP, a heat-stable DNA-binding protein, play a very important role in establishing and maintaining the differentiation state of liver cells as a transcription factor enriched in the liver. In order to identify its distribution, localization and function, immunocytochemical examination (ABC method) was done by using anti-C/EBP polypeptide antibodies 1103#, 425# in 20 normal human adult liver tissues, 5 neonatal liver tissues, 6 hepatitis tissues, 25 liver cirrhosis tissues, 80 hepatocellular carcinoma tissues (40 cases with associated surrounding non-tumor hepatic tissues) and 26 cholangiocarcinoma tissues (15 cases with associated surrounding non-tumor tissues). The results showed that C/EBP expression was restricted to terminally differentiated liver cells, and was very low or undetectable in poorly differentiated liver cells, such as liver tumor cells. Its expression also correlated with the grading of hepatocellular carcinoma. Besides, positive C/EBP stain could be found in all regenerating bile ductules. The C/EBP has a diffuse distribution which could be detected both in nuclei and in cytoplasm, but more abundant in cytoplasm. The results are in accordance with the concept that C/EBP plays an important role in establishing and maintaining the differentiation state of liver cells.
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PMID:[Determination on of C/EBP in human liver cancer, normal adult liver and various diseased liver tissues]. 817 74

In previous studies we have demonstrated molecular mimicry between the S peplomer protein of Mouse Hepatitis Virus (MHV) and Fc gamma Receptor (Fc gamma R) of IgG. Rabbit IgG, but not its F(ab')2 fragments, monoclonal rat and mouse IgG and the rat 2.4G2 anti-mouse Fc gamma R monoclonal antibody (mab) immunoprecipitated natural and recombinant MHV S protein. On the basis of a number of criteria, MHV S peplomer protein exhibits Fc IgG binding ability. We report here a molecular mimicry between the S peplomer protein of Bovine Coronavirus (BCV) and Fc gamma R. BCV S peplomer protein which belongs to the same antigenic subgroup as MHV also binds Fc portion of rabbit IgG and is immunoprecipitated by the 2.4G2 anti-Fc gamma R mab. In contrast, Transmissible Gastroenteritis Coronavirus (TGEV) and Infectious Bronchitis Virus (IBV) S peplomer proteins which represent two distinct antigenic subgroups of Coronaviridae do not bind rabbit IgG and do not react with anti-Fc gamma R mab. However, homologous swine IgG, but not its F(ab')2 fragments, immunoprecipitated from TGEV-infected cells a polypeptide chain with molecular mass of 195 kDa, identical to that immunoprecipitated by the T36 mab anti-TGEV S peplomer protein.
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PMID:Molecular mimicry between S peplomer proteins of coronaviruses (MHV, BCV, TGEV and IBV) and Fc receptor. 820 28

Hepatitis C virus (HCV) is the major cause of parenterally transmitted non-A, non-B hepatitis. The analysis of the genomic sequence of HCV has facilitated the development of a number of diagnostic assays for testing circulating antibodies in serum from patients with HCV infection. Besides the first-generation ELISA and RIBA, which employed the C100-3 non-structural polypeptide, second-generation tests employing both structural and non-structural polypeptides are being rapidly introduced. Several coded panels were employed in a comparative study of HCV-SP ELISA (utilizing a new synthetic peptide whose sequence was derived from the structural region) along with first- and second-generation tests. On the basis of the results, evidently antigens corresponding to the structural components of the virus are more sensitive and specific for the early detection of HCV antibodies than tests using non-structural epitopes. Additionally epitopes of the structural region elicit a very strong antibody response in laboratory animals. An example of one such application is the detection of HCV specific antigens in semen from patients diagnosed with non-A, non-B (NANB) hepatitis. Semen samples from 9 patients clinically diagnosed as having NANB hepatitis were tested by an ELISA using antibodies against HCV-specific structural antigens. The semen from all 9 patients had HCV-specific structural antigens in comparison to semen from 5 healthy donors. Semen from 5 of the 9 patients had significant levels of the HCV-specific antigen. This approach to detecting HCV antigens could, if rigorously tested, evolve into promising new assays for detecting HCV.
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PMID:Routine laboratory diagnosis of hepatitis C virus infection. 850 45

Sequence analysis of the mouse hepatitis virus, strain A59 (MHV-A59) genome predicts the presence of two papain-like proteases encoded within the first open reading frame of the replicase gene. The more 5' of these domains, the leader papain-like protease, is responsible for the cleavage of the amino terminal protein, p28. We have defined the core of this protease to between amino acids 1075 and 1344 from the beginning of ORF 1a. Deletion analysis coupled with in vitro expression, was used to study p28 cleavage by this leader protease. Expression of a series of deletion mutants showed processing of p28, albeit at lower levels in some of them. Reduced p28 production resulting from a 0.4 kb deletion positioned between p28 and the protease domain suggests an involvement of this region in catalytic processing. Some mutants display cleavage patterns indicative of a second cleavage site. Interestingly, this newly identified cleavage site maps to a position similar to the expected cleavage site of a p65 polypeptide detected in MHV-A59 infected cells. Mutagenesis of the catalytic H1272 residue demonstrates that both cleavages observed are mediated by the leader papain-like protease encoded in ORF 1a.
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PMID:Characterization of the leader papain-like protease of MHV-A59. 883 May 18

The polymerase gene of Mouse Hepatitis Virus strain JHM (MHV-JHM) encodes a polyprotein larger than 750 kilodaltons. This polyprotein is proposed to be processed by several viral proteinases into functional subunits. The amino-terminal subunit is p28, which is cleaved by the first viral papain-like proteinase domain. In this study, we identified the cleavage site of this papain-like cysteine proteinase by amino acid sequencing of radiolabeled polypeptide adjacent to p28. Proteolysis occurs between the glycine-247 and valine-248 dipeptide bond. To determine which amino acid residues are critical for proteolysis, we preformed site-directed mutagenesis on the coding sequences surrounding the cleavage site and assayed for the efficiency of cleavage of p28 in an in vitro transcription and translation system. We report that glycine-247 and arginine-246 are the most critical residues for efficient processing of p28.
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PMID:Proteolytic processing of the MHV polymerase polyprotein. Identification of the P28 cleavage site and the adjacent protein, P65. 883 May 20

Recent advances in molecular biology, in particular X-ray crystallography of the purified antigens A2 and DR1 and development of PCR-based HLA genotyping techniques, has revolutionized our understanding of immunogenetics and cellular immunology. The application of molecular immunogenetics has refined our understanding of HLA-encoded susceptibility and resistance to both autoimmune and chronic viral liver disease. Recent studies of autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) have identified substitutions of specific amino acid residues in the HLA DR beta-polypeptide (AIH and PSC) and DP beta-polypeptide (PBC) which may determine susceptibility to and resistance from disease. Although these models of HLA-encoded susceptibility in PSC and PBC are currently controversial, the model for AIH, based on lysine residue at DR beta 71 has recently been confirmed in an independent series. Data on chronic viral liver disease are less abundant, but a number of interesting observations are beginning to emerge. In the Gambia, resistance to chronic hepatitis B infection has been associated with the HLA DRB1*1302 allele, and in studies of patients with chronic hepatitis C virus infection DQA1*03 and DQB1*05 have been identified as a possible protective factors. Clarifying these HLA associations is not simply an academic pursuit; in addition to providing useful clues to the pathogenesis of these diseases, HLA associations may be important indicators of prognosis. In AIH, patients with the DRB1*0301-DRB3*0101 haplotype appear to have more severe disease than those with DRB1*0401, while in PSC, DRB3*0101 is associated with early onset of disease and DRB1*0401 may be a marker of more rapid disease progression. To date, our knowledge of immunogenetic susceptibility in liver disease is incomplete and further work is needed.
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PMID:Immunogenetics in liver disease. 890 22


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