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 unique region of murine hepatitis virus (MHV) mRNA 5 has two open reading frames. ORF 5a and ORF 5b, that encode small proteins of unknown function. In the experiments described here, we have used the in vitro translation of synthetic mRNAs to examine the expression of these ORFs. Our results show that a synthetic mRNA containing both ORFs is functionally bicistronic. More importantly, the expression of ORF 5b, but not ORF 5a, is maintained in a tricistronic mRNA containing an additional 5'-proximal ORF. Thus, in the context of the MHV mRNA 5 unique region, the initiation of protein synthesis on ORF 5b can occur independently of ribosomes that enter from the 5' end of the mRNA. We conclude that the translation of ORF 5b is mediated by the internal entry of ribosomes.
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PMID:Internal ribosome entry in the coding region of murine hepatitis virus mRNA 5. 796 13

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

To analyse the effect of strain-specific sequence variation on the antigenic properties of the protein encoded by the open reading frame 3 (ORF 3) of hepatitis E virus (HEV), two sets of short overlapping peptides spanning amino acids 91 to 123 of this protein from Burmese and Mexican strains were synthesized and tested with sera obtained from outbreaks of enterically transmitted non-A, non-B hepatitis in three different regions of the world (Mexico, Turkmenistan and Kenya). The data suggest strain-specific variation in the antigenic reactivity of the ORF 3 protein. The C-terminal region of this protein contains several antigenic epitopes located in the most variable positions. Individual sera were found to interact with different groups of epitopes from each set of peptides. The antigenic epitopes of the Mexican strain appear to be less conformation-dependent than those of the Burmese strain. The most immunoreactive epitope of the ORF 3 protein from the Mexican strain was localized at amino acid positions 95 to 101. The ORF 3 protein of the Burmese strain contains an immunodominant epitope at amino acid positions 112 to 117. Some of these short peptides may be useful for the development of a diagnostic assay to discriminate between the Burmese and Mexican strains.
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PMID:Comparative characterization of antigenic epitopes in the immunodominant region of the protein encoded by open reading frame 3 in Burmese and Mexican strains of hepatitis E virus. 812 61

Non-A, non-B hepatitis viruses have been implicated as the etiological agent(s) in up to 60% of patients with fulminant hepatitis. These agents are reported to induce a higher mortality than other causes of fulminant hepatitis. Hepatitis E virus (HEV) and hepatitis C virus (HCV) at present constitute the major identifiable non-A, non-B hepatitis agents. Of these, HEV has been established as the sole cause of epidemic hepatitis in Afro-Asian countries, and fulminant hepatitis has been recorded during such epidemics. However, in sporadic cases, the etiological role of HEV in fulminant hepatitis has remained uncertain. The role of HCV in acute liver disease and fulminant hepatitis remains unclear. The present study was undertaken to investigate the association of HEV and HCV in patients with fulminant hepatitis by direct detection of the viral genome using reverse transcription-polymerase chain reaction (RT-PCR). Serum samples from 50 serologically identified non-A, non-B fulminant hepatitis cases negative for cryptic hepatitis B virus (HBV) infection examined via PCR were tested for HEV and HCV RNA using RT-PCR. For HEV primers from the nonstructural region (ORF-1) were used, and for HCV primers from the highly conserved 5' untranslated regions were used. The products were analysed using agarose gel electrophoresis and confirmed by hybridisation with radiolabelled internal oligonucleotide probes. HEV was detected in 31 (62%) of the 50 fulminant non-A, non-B hepatitis cases. In 18 (36%) cases, HCV RNA was detected. In 11 (22%) of the HCV cases, the HEV genome was also amplified. In 20 (40%) cases, HEV was detected alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Etiological role of hepatitis E virus in sporadic fulminant hepatitis. 815 8

The sequence of the HCV 229E gene 1 has been determined and compared with the homologous sequences of the murine hepatitis virus and the avian infectious bronchitis virus. The coding sequence of gene 1 is 20,273 nucleotides in length. Within this coding region are two large open reading frames, ORF 1a (4,086 codons) and ORF 1b (2,687 codons) which overlap by 40 nucleotides. In the overlapping region, the genomic RNA can be folded into a pseudoknot structure, an element which is known to mediate -1 ribosomal frame-shifting in other coronaviruses. Assuming that -1 frame-shifting occurs at the HCV sequence UUUAAAC (nucleotides 12,514-12,520), the ORF 1a - ORF 1b product is predicted to be 6,758 amino acids in length. Our sequence analysis of the HCV 229E gene 1 has revealed a high degree of similarity within the ORF 1b of HCV, MHV and IBV, whereas ORF 1a is much less conserved. Elements which are believed to be necessary for specific (e.g. frame-shifting) and general (e.g. NTP-binding/helicase) transcriptional functions have been identified. This study completes the genomic sequence of HCV 229E which is 27.27 kb long and one of the largest known RNA genomes.
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PMID:Characterization of the human coronavirus 229E (HCV 229E) gene 1. 820 74

The recently characterized fecal-orally transmitted agent of hepatitis E (formerly known as enterically transmitted non-A, non-B hepatitis) has been determined to be a new type of positive strand RNA virus. The complete sequencing of four different geographic isolates of the hepatitis E virus (HEV) has confirmed a similar genetic organization not previously recognized in nonenveloped positive strand RNA viruses. The approximately 7.5 kb RNA genome (including polyA tail) has nonstructural genes located at the 5' end and structural genes at the 3' end. Expression of these viral genes occurs in at least 3 different forward open reading frames. The largest open reading frame begins 27 nucleotides (nt) downstream of the apparent noncoding 5' end and extends 5,079 nt. Multiple nonstructural gene motifs/domains have been recognized in this 5' ORF1 including a methyltransferase, a papain-like protease, a helicase and the RNA-dependent, RNA polymerase. The second major ORF2 begins 37nt downstream of ORF1 and extends 1980 nt before terminating 65 nt upstream of the polyadenylation site. A third ORF of only 369 nt was identified by immunoscreening experiments as encoding an immunogenic epitope of the virus. Expression of the downstream ORF2 may occur through internal subgenomic RNA initiation at a sequence element found to have homology to internal RNA initiation sequences in Sindbis virus. This element in the HEV genome maps near the apparent 5' end of one of two identified subgenomic messages. The genomic organization and expression of HEV will be discussed and a hypothesis presented regarding the viral replication strategy.
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PMID:Molecular organization and replication of hepatitis E virus (HEV). 821 99

Gene 1, the putative RNA replicase gene of coronaviruses, is expressed via two large overlapping open reading frames (ORF 1a and ORF 1b). We have determined the nucleotide sequence of ORF 1a, encoded within the first 13.7 kb of gene 1, for the coronavirus mouse hepatitis virus strain A59 (MHV-A59). Putative papain-like protease domains, a picornavirus 3C-like protease domain, two hydrophobic domains, and a domain "X" of unknown function, previously identified in other coronaviruses (1-3), are also present in ORF 1a of MHV-A59. Comparison between the ORF 1a sequence of MHV-A59 and the published sequence of the JHM strain of MHV (2) showed a high degree of similarity with the exception of several short regions. We sequenced one region of MHV-JHM that contained an 18 amino acid insertion relative to A59 and four other regions in which the sequences of the two strains differed. The MHV-2 and MHV-3 strains were also sequenced in some of these regions. Our analysis confirmed the presence of only one heterogeneous region in ORF 1a of MHV-A59 and MHV-JHM which is also present in MHV-2. Our findings indicate the need to modify the published sequence of MHV-JHM.
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PMID:Mouse hepatitis virus strain A59 RNA polymerase gene ORF 1a: heterogeneity among MHV strains. 829 Dec 54

The coronavirus mouse hepatitis virus-A59 (MHV-A59) encodes a serine-like proteinase (3C-like proteinase or 3CLpro) in ORF 1a of gene 1 between nucleotides 10,209 and 11,114. We previously have demonstrated that proteins expressed in vitro from a cDNA clone of the 3CLpro region possess proteinase activity, and that the proteinase is able to cleave substrate in trans. We sought to determine if the 27-kDa in vitro cleavage product (p27) was an active form of the 3CLpro and whether this was consistent with the 3CLpro expressed in virus-infected cells. Antibodies directed against the 3CLpro domain detected 27-kDa MHV proteins in vitro and in MHV-A59-infected cells. The 27-kDa proteins were able to cleave substrate in trans without other protein cofactors or supplemental membranes, and the p27 proteinase activity was retained after purification by immunoprecipitation and gel electrophoresis. When p27 was expressed in vitro with portions of the amino-and carboxy-terminal flanking domains (MP1 and MP2), p27 was not liberated by cls cleavage. The proteolytic activity of the 27-kDa proteins was inhibited by a variety of cysteine and serine proteinase inhibitors, and was eliminated by the cysteine proteinase inhibitor E64d. These results indicate that the 27-kDa protein is a mature proteinase in MHV-A59-infected cells, and that appropriate processing of this molecule occurs in vitro.
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PMID:Intracellular and in vitro-translated 27-kDa proteins contain the 3C-like proteinase activity of the coronavirus MHV-A59. 880 21

We have investigated the intracellular localization of several of the proteolytic cleavage products derived from the 5' portion of mouse hepatitis virus (MHV) gene 1. Antisera UP1 recognizes the N-terminal ORF1a cleavage product p28. Immunofluorescent staining of cells with this antisera resulted in a diffuse punctate pattern of cytoplasmic staining, indicating that this protein is widely distributed in the cytoplasm. Immunofluorescent staining of infected cells with antisera which recognize polypeptides p240 and p290 stained discrete vesicular perinuclear structures suggesting that these proteins localized to the Golgi. This was confirmed by double immunofluorescent staining of BHK cells expressing the MHV receptor (BHK-R) with a Golgi specific antibody in addition to our anti-MHV ORF1a antibodies. Antisera UP102 recognizes p28 and the immediately downstream p65 gene product. Double immunofluorescent staining of MHV infected BHK-R cells with UP102 labeled discrete vesicular structures overlapping the Golgi complex. In addition there was punctate staining more widely distributed in the cytoplasm. The simplest explanation for this pattern is that p65 is also localized to the Golgi region of the cell, whereas p28 is more widespread. Plasmids containing the first 4.7 and 6.75 kb of ORF 1a have been expressed using the coupled vaccinia virus-T7 polymerase system. Images obtained by immunofluorescent staining of transfectants with our anti-ORF1a antisera are similar to those obtained during infection with A59. These studies indicate that the signals which direct p290 to the Golgi are likely contained between the C-terminus of p28 and ORF1a residue 1494.
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PMID:Intracellular localization of polypeptides encoded in mouse hepatitis virus open reading frame 1A. 883 Apr 88

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


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