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)

HepCV is the major cause of NANB PT hepatitis and is also implicated as the cause in a large proportion of sporadic cases of NANBH. Chronic infection with HepCV has also been linked to the development of hepatocellular carcinoma. Chimpanzees and marmosets are the only animals found to be experimentally infectable and the virus has not been propagated in any cell culture system. HepCV is an enveloped virus with a diameter of 30-60 nm and a 10-kb positive-stranded RNA genome. Its genome organization resembles that of the flaviviruses and pestiviruses. A 5'-untranslated segment of 341 nucleotides precedes a continuous ORF of 9030/9033 nucleotides which is followed by a 54 nucleotides long 3'-non-coding segment. Further work is required to resolve the question of whether the genomic RNA possesses a 3'-poly(U) or poly(A) tail. The genome also carries an internal poly(A) segment towards the 5'-end of its ORF. Genomic RNA is probably translated into a single polyprotein of 3010/3011 amino acids which is processed into functional proteins. The viral proteins have not been identified, but on the basis of the predicted amino acid sequences, hydrophobicity plots, location of potential glycosylation sites and similarities of these properties to those of pesti- and flaviviruses, the following genome organization has been predicted. The predicted viral structural proteins, a nucleocapsid protein and two envelope glycoproteins are located at the amino-terminal end of the polyprotein. They are followed by a highly hydrophobic protein and proteins that exhibit proteinase, helicase and replicase domains and thus are probably involved in RNA replication and protein processing. The replicase domain is located close to the carboxy terminus of the polyprotein. Although the overall nucleotide and amino acid homologies between HepCV and pestiviruses are low, a number of similarities exist that point to a closer ancestral relationship to the latter than the flaviviruses. First, the 5'-untranslated segment of the HepCV genome resembles that of the pestivirus genomes in size and presence of several short ORFs and it contains several segments with high nucleotide homology. Second, the two putative envelope glycoproteins of HepCV resemble two of the three putative envelope glycoproteins of the pestiviruses. Because its genome organization and predicted virion structure closely resemble those of the flaviviruses and pestiviruses, HepCV has been proposed to be placed in the family Flaviviridae.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hepatitis C virus. 165 96

The 5'-most gene, gene 1, of the genome of murine coronavirus, mouse hepatitis virus (MHV), is presumed to encode the viral RNA-dependent RNA polymerase. We have determined the complete sequence of this gene of the JHM strain by cDNA cloning and sequencing. The total length of this gene is 21,798 nucleotides long, which includes two overlapping, large open reading frames. The first open reading frame, ORF 1a, is 4488 amino acids long. The second open reading frame, ORF 1b, overlaps ORF 1a for 75 nucleotides, and is 2731 amino acids long. The overlapping region may fold into a pseudoknot RNA structure, similar to the corresponding region of the RNA of avian coronavirus, infectious bronchitis virus (IBV). The in vitro transcription and translation studies of this region indicated that these two ORFs were most likely translated into one polyprotein by a ribosomal frameshifting mechanism. Thus, the predicted molecular weight of the gene 1 product is more than 800,000 Da. The sequence of ORF 1b is very similar to the corresponding ORF of IBV. In contrast, the ORF 1a of these two viruses differ in size and have a high degree of divergence. The amino acid sequence analysis suggested that ORF 1a contains several functional domains, including two hydrophobic, membrane-anchoring domains, and three cysteine-rich domains. It also contains a picornaviral 3C-like protease domain and two papain-like protease domains. The presence of these protease domains suggests that the polyprotein is most likely processed into multiple protein products. In contrast, the ORF 1b contains polymerase, helicase, and zinc-finger motifs. These sequence studies suggested that the MHV gene 1 product is involved in RNA synthesis, and that this product is processed autoproteolytically after translation. This study completes the sequence of the MHV genome, which is 31 kb long, and constitutes the largest viral RNA known.
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PMID:The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase. 184 89

Hepatitis viruses A, B, C, D, and E have not accounted for all cases of hepatitis, hence "non A-E" agent(s) might be implicated. A set of new viruses (GBV-A, -B, and -C) whose genomes have been sequenced, are being investigated as possible causes of non A-E hepatitis. We investigated six cases of fulminant hepatitis of unknown aetiology for the presence of GBV-C genome in their serum, and three showed positive signals by semi-nested PCR using primers derived from the NS3/helicase region. Nucleotide sequence analyses confirmed these signals to be derived from a GBV-C sequence. The results suggest the importance of GBV-C in the aetiology of fulminant hepatitis.
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PMID:Detection of the GBV-C hepatitis virus genome in serum from patients with fulminant hepatitis of unknown aetiology. 862 32

Two viruses, GB virus A (GBV-A) and GB virus B (GBV-B), were recently identified in the GB hepatitis agent. Human sera containing antibodies that recognize GBV-A and/or GBV-B recombinant proteins were subjected to polymerase chain reaction studies with degenerate oligonucleotides capable of amplifying a segment of the putative helicase genes from GBV-A, GBV-B or hepatitis C virus. Novel sequences related to members of the Flaviviridae were identified in sera from 12 individuals including 4 individuals with hepatitis. The limited nucleotide sequence identity between GBV-A, GBV-B and HCV sequences suggests that a novel virus, tentatively named GB virus C, may be responsible for some cases of non-A, non-B, non-C, non-D, non-E hepatitis.
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PMID:Isolation of novel virus-like sequences associated with human hepatitis. 758 24

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

Two flavivirus-like viruses, GB virus-A (GBV-A) and GB virus-B (GBV-B), were recently identified in the GB hepatitis agent, and are distinct from the hepatitis A to E viruses. The putative helicase domain of GBV-A and GBV-B was found to have amino acid sequence homology with hepatitis C virus (HCV), and distantly, is also related to pestiviruses, flaviviruses, and plant viruses. A phylogenetic tree construction showed that GBVs and HCV are closely related, and they are clustered with pestiviruses, flaviviruses and plant viruses in that order.
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PMID:Evolutionary relationship of hepatitis C, pesti-, flavi-, plantviruses, and newly discovered GB hepatitis agents. 855 7

RNA of a non-A to E hepatitis virus identified recently and designated provisionally GB virus C(GBV-C), was sought in patients in Indonesia by reverse-transcription polymerase chain reaction with nested primers deduced from a helicase-like region. GBV-C RNA was detected in 32 (55%) of 58 patients on maintenance hemodialysis at a frequency significantly higher (P < 0.001) than that in seven (5%) of 149 patients with chronic liver disease. Co-infection with hepatitis C virus was observed in 26 (81%) of the 32 patients on hemodialysis and in five (71%) of the seven patients with liver disease who were infected with GBV-C. Complete identity was observed in a sequence of 100 base pairs in the helicase-like region for GBV-C cDNA clones from some patients on maintenance hemodialysis. These results indicate that the patients on hemodialysis would be at high risk for GBV-C infection, which would be transmitted by transfusion and patient-to-patient routes.
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PMID:Infection with GB virus C (GBV-C) in patients with chronic liver disease or on maintenance hemodialysis in Indonesia. 881 73

Recently, a novel virus, tentatively designated GB virus (GBV-C) was identified in patients with hepatitis. The frequency of this novel virus infection was therefore investigated in 58 patients with chronic hepatitis B virus (HBV) infection and in 74 patients with chronic hepatitis C virus (HCV) infection who had received orthotopic liver transplantation (OLT) because of decompensated liver cirrhosis. Before OLT, GBV-C sequences were found by reverse transcription nested polymerase chain reaction with primers derived from the helicase-like region in six (10%) of the HBV- and in six (8%) of the HCV-infected patients. Specificity of the polymerase chain reaction products was confirmed in eight of them by direct sequencing. Pretransplant GBV-6 viremia was associated with posttransplant viremia in 75% of patients. The comparison of GBV-C nucleotide and amino acid sequences within the helicase-like region revealed that pre- and posttransplant sequences differed only in 0-7 nucleotide exchanges, and with the exception of one, all of them were silent mutations. After OLT, 29% of the HBV- infected and 12% of the HCV-infected patients became GBV-C positive,indicating a high rate of "de novo" GBV-C infection. By correlating the GBV-C status with the frequency of the occurrence of graft hepatitis in both groups of patients, it became evident that posttransplant GBV-C viremia did not increase the risk for this clinical condition. However, we found a significantly higher percentage of hepatocellular carcinoma in patients with pre-OLT GBV-C/HCV coinfection compared with patients with HCV infection alone (5/6 vs. 16/68;P<0.01).
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PMID:GB virus C infection in patients with chronic hepatitis B and C before and after liver transplantation. 882 65

Recently, sequences from a novel virus, termed GB virus C (GBV-C), were identified in serum from several patients with cryptogenic hepatitis. In the present study, the nucleotide sequence of this virus has been extended to near-genome length. GBV-C encodes a putative single large polyprotein in which the structural proteins are positioned at the N-terminal end, with the non-structural proteins located at the C-terminal end. Amino acid sequence analysis of this large polyprotein reveals the presence of protease, helicase, and replicase motifs. Sequence alignments of the polyprotein followed by phylogenetic analyses suggest that GBV-C is a member of the Flaviviridae, most closely related to the recently described GB virus A.
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PMID:Sequence and genomic organization of GBV-C: a novel member of the flaviviridae associated with human non-A-E hepatitis. 882 12


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