Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis A virus is an enteric picornavirus. Its genome is a single stranded RNA molecule of positive-strand polarity of 7478 bases. This sequence codes for a polyprotein which is processed to give rise to viral proteins VP-1, VP-2, VP-3 and others. Hepatitis B virus, a major worldwide infectious and cancer promoting agent contains a DNA genome of 3226 base pairs that replicates by a reverse transcriptase via an RNA intermediate. Extensive sequencing and expression experiments have revealed four major genes named surface, core, polymerase and X which are coded in more than one reading frame. Furthermore, within a frame, proteins are expressed from multiple initiation codons resulting in several related products. The viral genome of hepatitis C virus (nonA-nonB), an elusive major infectious agent, has recently been cloned. This genome is a single positive-stranded RNA of at least 10,000 bases which codes for several antigens, some of them associated specifically with nonA-nonB hepatitis infections. The hepatitis D (delta) viral agent, an infectious agent requiring a hepadnarious for propagation, contains a covalently closed circular single-stranded RNA genome of 1167 nucleotides. This genome encodes the protein p24 and p27 that bind specifically to antisera from patients with chronic hepatitis D infections.
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PMID:Hepatitis A, B, C, D and E viruses: structure of their genomes and general properties. 222 69

On the basis of the complete nucleotide sequence of the single-stranded, covalently closed circular hepatitis delta virus RNA genome (K.-S. Wang, Q.-L. Choo, A. J. Weiner, J.-H. Ou, R. C. Najarian, R. M. Thayer, G. T. Mullenbach, K. J. Denniston, J. L. Gerin, and M. Houghton, Nature [London] 323:508-514, 1986 [Author's correction, 328:456, 1987]), five long open reading frames (ORFs) encoding polypeptides containing a methionine proximal to the amino terminus were expressed in bacteria. Only polypeptides encoded by the antigenomic ORF5 cross-reacted with antisera obtained from patients with hepatitis delta virus infections. Immunological analysis of viral extracts and the recombinant ORF5 polypeptides synthesized in bacteria and yeast cells revealed that ORF5 encodes the immunogenic epitope(s) shared by both hepatitis delta viral polypeptides p27 delta and p24 delta and probably represents the complete structural gene for p27 delta and p24 delta. We also present evidence that ORF5 encodes the hepatitis delta antigen, an antigen originally found in the nuclei of hepatocytes of infected individuals (M. Rizzetto, M. G. Canese, S. Arico, O. Crivelli, F. Bonino, C. G. Trepo, and G. Verme, Gut 18:997-1003, 1977). A comparison of the primary structure of the predicted hepatitis delta antigen polypeptides with that of the core antigen of the hepatitis B virus shows that these polypeptides are very dissimilar.
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PMID:A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta. 244 91

Three major polypeptides of hepatitis B surface antigen (HBsAg), with mol. wt. 22,000 (p22), 27,000 (p27) and 68,000 (p68), were separated by preparative SDS-PAGE. These three peptides as well as intact HBsAg were found to have almost identical amino acid compositions and carbohydrate was detected in p27 and p68 by PAS staining. Papain treatment of p68 produced two distinct peptides p27 and p22. Moreover, when an artificial mixture of p27 and p22 in a ratio of 1:1 was treated with 0.2 M-periodate for 30 min at 37 degrees C, only p22 was detectable. These results suggest that p68 is composed of p27 and p22, and that p27 is a glycosylated product of p22. Thus, from the evidence obtained, it is possible that p22 (22,000 peptide) is the minimum size of the unique hepatitis B virus (HBV) gene product involved.
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PMID:Glycopeptide composition of hepatitis B surface antigen. 624 40

The relationships among the core antigen polypeptides of hepatitis B virus (HBV) and ground squirrel hepatitis virus (GSHV) were studied using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping. The major core antigen polypeptides of liver-derived HBV (p22) and GSHV (p20.5) shared 56% of the spots in their peptide maps. Comparison of hepatitis B core antigen (HBcAg) p19 or ground squirrel hepatitis core antigen (GSHcAg) p16.5 with their respective major polypeptides indicated that these components probably resulted from cleavage of the major polypeptide of each virus. Other polypeptides smaller than the major component of each virus were often faint on polyacrylamide gels and probably resulted from the cleavage or degradation of components larger than p22 of HBcAg or p20.5 of GSHcAg, since their peptide maps contained spots unique to these high-molecular-weight components. p26 of GSHcAg and p27.5 of HBcAg shared approximately two-thirds of the spots on their peptide maps with those of their respective major core polypeptides. Furthermore, p37.5 of GSHcAg and p40 of HBcAg shared about 60% homology with their respective major polypeptides, and also shared many of the spots that were unique to p26 of GSHcAg or p27.5 of HBcAg but were not found in the peptide map of their respective core antigen polypeptides. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis bands larger than 40,000 daltons were variably present, and peptide mapping indicated that these were aggregates of various smaller core antigen-associated polypeptides. The results suggest that p40 of HBcAg and p37.5 of GSHcAg are the largest unique polypeptides in these core particles, and that they are encoded for by the genome of each virus. That a subset of the spots unique to p40 or p37.5 was also found in p27.5 of HBcAg or p26 of GSHcAg, respectively, as compared to the major core polypeptides, also suggests that p27.5 and p26 are unique proteins encoded by the genome of each virus. It is proposed that the core antigen gene of each virus is larger than that which would encode the major polypeptide of each virus, and that the genetic organizations of the core genes of HBV and GSHV are very similar.
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PMID:Core particles of hepatitis B virus and ground squirrel hepatitis virus. I. Relationship between hepatitis B core antigen- and ground squirrel hepatitis core antigen-associated polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping. 710 37

Hepatitis delta virus is a satellite of the hepatitis B virus which provides the surface antigen for the viral coat. The genome of the hepatitis delta virus consists of a single-stranded, circular RNA of 1679 nucleotides which forms a rod structure due to a high extent of self homology and which replicates via synthesis of an antigenomic RNA in a rolling circle mechanism similar to plant viroids. The antigenomic RNA contains the open reading frame for the delta-antigen which exists in two isoforms, p24 and p27. The formation of these two isoforms is explained by RNA editing at nucleotide 1012 which changes the stop translation codon UAG at amino acid residue 196 into the codon UGG for tryptophan and extends the open reading frame for the synthesis of p27. In order to investigate whether the editing occurs cotranscriptionally during RNA replication or is a posttranscriptional base modification in the genomic or antigenomic RNA, replication defective deletion mutants of the HDV genome were constructed and expressed in COS-7 cells. Editing was demonstrated in non-replicating fragments of genomic HDV RNA but not in antigenomic HDV RNA fragments. The sequences from nucleotide position 337-1200 of the genomic RNA were sufficient to enable low levels of editing. Editing at position 1012 required the opposite strand of the RNA rod from nucleotide position 337-783. Replicating circular HDV RNA was much more efficiently edited than non-replicating full length genomic HDV RNA. Expression of delta-antigen in trans did not complement the low editing efficiency of replication defective genomic HDV RNA. These results demonstrate posttranscriptional U to C editing in the genomic HDV RNA and exclude misincorporation during HDV RNA replication as the editing mechanism. The minimal structural requirements for HDV RNA editing reside between nucleotide position 337-1200.
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PMID:Requirements for editing in the genomic RNA of hepatitis delta virus. 774 56

Hepatitis delta virus (HDV) packaging requires prenylation of the HDV large protein (p27), as well as a direct protein-protein interaction between HDV proteins and hepatitis B virus (HBV) envelope protein domains. To investigate this interaction, we have analysed the binding capacity of baculovirus-expressed delta p24 and p27 proteins to synthetic peptides specific for the HBV envelope. Although a higher degree of binding was observed with p27, both p24 and p27 could bind HBV envelope peptides. One such peptide corresponded to residues 56-80 located in the cytosolic loop of the small HBV envelope protein, and another corresponded to 23 carboxy-terminal residues of the pre-S1 specific to the large HBV envelope protein. This indicates that in addition to p27, p24 may contribute to packaging of HDV through a protein-protein interaction with HBV envelope domains, and that an interaction between the pre-S1 polypeptide and delta proteins may play a role in infectivity.
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PMID:Interaction between hepatitis delta virus-encoded proteins and hepatitis B virus envelope protein domains. 960 26

Hepatitis delta virus (HDV) superinfection of hepatitis B virus carriers causes severe liver disease and results in a high rate of chronicity. So far, neither sufficient therapy nor vaccines to prevent HBV carriers from superinfection are available. A good model to test vaccine candidates is the woodchuck chronically infected with the woodchuck hepatitis virus (WHV); the woodchuck can be superinfected with HDV and shows a course of infection similar to that of patients. Different strategies have been investigated to establish a protective vaccine against HDV superinfection. Both proteins of HDV (HDAg p24 and p27), which differ only in the C-terminal amino acid sequence, have been used as vaccine candidates. Synthetic peptides derived from B cell epitopes of HDAg and HDAg p24 expressed in Escherichia coli, yeast, or baculovirus have been used to immunize woodchucks. The protein immunization induced a specific antibody response, however, no protection from HDV superinfection was achieved. Vaccinations with vaccinia virus expressing HDAg p24 or p27 and DNA immunization with vectors expressing p24 were also not able to induce a protective immune response, but seemed to modulate the course of HDV superinfection. Thus, new strategies to develop a vaccine to prevent HDV superinfection are needed.
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PMID:Vaccination against hepatitis delta virus infection: studies in the woodchuck (Marmota monax) model. 1150 76

Deranged expression of cell cycle modulators has been reported to contribute to the development and progression of hepatocellular carcinoma (HCC). However, their expression patterns remain poorly understood in hepatitis B virus (HBV)-related HCC, which constitutes about 65-70% of HCC in Korea. The aims of this study were to evaluate the expressions of G1-S modulators in HBV-related HCCs and dysplastic nodules (DNs), and to correlate with the histopathologic features of HCCs. Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27, p21, p16, Rb, and PCNA proteins were investigated in 80 HCCs and 22 DNs. Cyclin D1 overexpression showed positive relationships with advanced tumor stage, poor differentiation, larger tumor size, microvascular invasion, intrahepatic meta-stasis, no tumor capsule formation, infiltrative growth, aberrant p53 expression, and high PCNA labeling index (LI) of HCC (p<0.05). Aberrant p53 expression showed positive relationship with poor differentiation of HCC (p<0.01). Expression of cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were lower in HCCs with intrahepatic metastasis (p<0.05). Cyclin D1 overexpression and aberrant p53 expression could be associated with the progression of HBV-related HCC, and might have a less crucial role in the DN-HCC sequence. In addition, elevated expression of p27 and p16 proteins might have inhibitory action to the intrahepatic metastasis of HBV-related HCC.
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PMID:Expression of the G1-S modulators in hepatitis B virus-related hepatocellular carcinoma and dysplastic nodule: association of cyclin D1 and p53 proteins with the progression of hepatocellular carcinoma. 1151 87

Previously, we have linked prolonged intense mitogen-activated protein kinase (MAP kinase; MAPK) signaling in hepatocytes to increased expression of p21(Cip-1/WAF1/MDA6) (p21) and p16(INK4a) (p16), that leads to a p21-dependent growth arrest. In this study, we investigated the impact of hepatitis B virus X protein (pX) expression on MAPK-modulated cell cycle progression in primary mouse hepatocytes. In hepatocytes, expression of pX enhanced protein levels of p21 and p27, but not of p16. The elevated levels of p21 and p27 correlated with reduced DNA synthesis in wild-type (+/+) hepatocytes and with a weak stimulation of DNA synthesis in p21 null (-/-) cells. Antisense p27 messenger RNA (mRNA) (p27as) increased DNA synthesis in +/+ and p21 -/- cells, and pX blunted this effect in +/+ cells. In p21 -/- cells, however, p27as permitted pX to further stimulate DNA synthesis. These data argue that a reduced ability to enhance expression of both p21 and p27 is required to fully reveal the growth-potentiating properties of pX. This finding also implies that depending on the functional status of the p21 and p27 genes, expression of pX can have 2 very different effects on hepatocyte proliferation. Prolonged intense MAPK signaling reduced DNA synthesis in +/+ cells and enhanced DNA synthesis in p21 -/- cells. The enhancement of DNA synthesis in p21 -/- cells was blocked by pX, and the effect of pX was abrogated by p27as. Furthermore in p21 -/- cells, overexpression of p16 blocked MAPK-stimulated DNA synthesis, and this effect was partially reversed by p27as. These data argue that p27 can also cooperatively interact with p16 to inhibit DNA synthesis in hepatocytes. Collectively, our findings show that reduced expression of p16, p21, and p27, which can occur during hepatocellular carcinoma, enhances the ability of MAPK signaling and pX to cause proliferation in hepatocytes. Thus loss of cyclin kinase inhibitor function may play an important role in the process of tumor progression after chronic hepatitis B virus infection.
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PMID:Hepatitis B virus X protein increases expression of p21(Cip-1/WAF1/MDA6) and p27(Kip-1) in primary mouse hepatocytes, leading to reduced cell cycle progression. 1167 61

The HBx (X protein of hepatitis B virus) is a promiscuous transactivator implicated to play a key role in hepatocellular carcinoma. However, HBx-regulated molecular events leading to deregulation of cell cycle or establishment of a permissive environment for hepatocarcinogenesis are not fully understood. Our cell culture-based studies suggested that HBx had a profound effect on cell cycle progression even in the absence of serum. HBx presence led to an early and sustained level of cyclin-cdk2 complex during the cell cycle combined with increased protein kinase activity of cdk2 heralding an early proliferative signal. The increased cdk2 activity also led to an early proteasomal degradation of p27(Kip1) that could be reversed by HBx-specific RNA interference and blocked by a chemical inhibitor of cdk2 or the T187A mutant of p27. Further, our co-immunoprecipitation and in vitro binding studies with recombinant proteins suggested a direct interaction between HBx and the cyclin E/A-cdk2 complex. Interference with different signalling cascades known to be activated by HBx suggested a constitutive requirement of Src kinases for the association of HBx with these complexes. Notably, the HBx mutant that did not interact with cyclin E/A failed to destabilize p27(Kip1) or deregulate the cell cycle. Thus HBx appears to deregulate the cell cycle by interacting with the key cell cycle regulators independent of its well-established role in transactivation.
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PMID:HBx-dependent cell cycle deregulation involves interaction with cyclin E/A-cdk2 complex and destabilization of p27Kip1. 1693 21


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