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)

The PLC/PRF/5 cell line derived from a human hepatoma produces hepatitis B surface antigen (HBsAg) in 22-nm particles of the same buoyant density as those found in the serum of infected patients. The HBsAg particles from this cell line were labeled with [35S]methionine and purified, and the polypeptides were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with those of serum-derived particles. The two major polypeptides of serum-derived HBsAg particles (p20 and p23) were found in the same relative amounts in the particles from the cell line. The three smallest of the five minor components observed in HBsAg particles from serum were present in particles from the cell line. These polypeptides (p31, p36, and p43), as well as p20 and p23, were precipitated with anti-HBs-containing serum. The two largest polypeptides of serum particles (p49 and p66) were not detected in particles from these cells. When the PLC/PRF/5 HBsAg particles were radiolabeled with tritiated sugars, p23, and not p20, was found to contain radioactivity, indicating that the pattern of polypeptide glycosylation is similar to that of serum HBsAg. None of the other possible gene products of hepatitis B virus was detected in the PLC/PRF/5-derived HBsAg particles, in the cells, or in the cell supernatants.
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PMID:Polypeptides of hepatitis B virus surface antigen produced by a hepatoma cell line. 9 75

Hepatitis B surface antigen in the form of 22 nm spherical particles (and tubular forms) is excess virus coat protein. Guidelines for the preparation of the 22 nm spherical particles (and their separated polypeptides) derived from the plasma of asymptomatic human carriers, were suggested by the WHO Expert Committee on Viral Hepatitis in 1977, and the proposed requirements for the 22 nm hepatitis B particle vaccine were published by the WHO Expert Committee on Biological Standardisation in 1981 and revised in 1983. Such preparations have been tested for safety and protective efficacy and many clinical trials with the plasma-derived vaccine have demonstrated the immunogenicity, high protective efficacy and safety of the currently licensed preparations. Polypeptide vaccines, derived from the surface antigen from any source, have several advantages which include precise biochemical characterisation, exclusion of genetic material of viral origin, exclusion of host or donor-derived substances and enhanced potency. A polypeptide vaccine in micellar form has been developed in London. The applications of recombinant DNA technology permit the isolation, purification and selective amplification of almost any individual segment of DNA from practically any organism in convenient biological systems such as bacteria, yeast, or any other cell including mammalian cells. Considerable progress has been made with vaccines prepared from antigen expressed in yeast (Saccharomyces cerevisiae). Cloning of the DNA of hepatitis B virus has resulted in sequencing of nucleotides and mapping of the amino acids of antigens. Information obtained from the sequencing of the 226 amino acids of hepatitis B surface antigen has led to the development of chemically synthesised peptides corresponding to amino acid sequences predicted from the nucleotide map. Several such synthetic peptides, when linked to potent adjuvants elicit antibodies in experimental animals which react with the surface antigen. The potential of pure chemically synthetic vaccines against hepatitis B, and other infectious agents, is under intensive investigation since such vaccines should be chemically well-defined, uniform, safe and cheap to produce. Studies have been carried out recently using a chemically synthetic peptide in a linear and in a cyclical form corresponding to the amino acids sequence 139-147 of the major polypeptide I of hepatitis B surface antigen. The synthetic antigens and the native polypeptide complex p23-gp28 purified from hepatitis B surface antigen in plasma were used for the measurement of affinity of the antibody to the surface antigen (anti-HBs) in human sera.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Subunit, recombinant and synthetic hepatitis B vaccines. 391 63

The immunoprophylaxis of hepatitis B is hampered by the lack of a technique for growing hepatitis B virus (HBV) in tissue culture. Plasma from persistently infected individuals, one source of viral antigen, contains characteristic 22-nm spherical particles which share a common antigen (the hepatitis B surface antigen or HBsAg) with the outer envelope of the 42-nm double-shelled DNA virus. Highly purified inactivated 22-nm particles have been shown to be safe and to confer protective immunity against HBV in a recent large-scale clinical trial. We have already described the extraction from the particles of a complex of two proteins which are antigenic determinants of HBV--the polypeptide with molecular weight (MW) between 22,000 and 24,000 (called p23) and the glycosylated polypeptide (called gp28) with MW in the range 26,000--29,000 which is thought to be the glycosylated form of p23. We now report the preparation from this complex of water-soluble protein micelles which may be a suitable basis for a second-generation hepatitis B vaccine.
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PMID:Hepatitis B polypeptide vaccine preparation in micelle form. 616 84

Water-soluble protein micelles consisting of the 28,000 (gp28) and 23,00 (p23) molecular weight polypeptide complex of hepatitis B surface antigen can be readily prepared from human plasma containing the surface antigen and other markers of infection with hepatitis B virus. The antigenic activity of the polypeptides was preserved throughout the process of solubilisation and reassociation into micelles. Such preparations are therefore eminently suitable as "second generation" hepatitis B vaccines.
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PMID:Preparation of hepatitis B polypeptide micelles from human carrier plasma. 707 83

Assembly of hepadnaviruses depends on the formation of a ribonucleoprotein (RNP) complex comprising the viral polymerase polypeptide and an RNA segment, epsilon, present on pregenomic RNA. This interaction, in turn, activates the reverse transcription reaction, which is primed by a tyrosine residue on the polymerase. We have shown recently that the formation of this RNP complex in an avian hepadnavirus, the duck hepatitis B virus, depends on cellular factors that include the heat shock protein 90 (Hsp90). We now report that RNP formation also requires ATP hydrolysis and the function of p23, a recently identified chaperone partner for Hsp90. Furthermore, we also provide evidence that the chaperone complex is incorporated into the viral nucleocapsids in a polymerase-dependent reaction. Based on these findings, we propose a model for hepadnavirus assembly and priming of viral DNA synthesis where a dynamic, energy-driven process, mediated by a multi-component chaperone complex consisting of Hsp90, p23 and, potentially, additional factors, maintains the reverse transcriptase in a specific conformation that is competent for RNA packaging and protein priming of viral DNA synthesis.
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PMID:Hepadnavirus assembly and reverse transcription require a multi-component chaperone complex which is incorporated into nucleocapsids. 900 68

Hepatitis B viruses replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Replication is initiated de novo and requires formation of a ribonucleoprotein complex comprising the viral reverse transcriptase (P protein), an RNA stem-loop structure (epsilon) on the pgRNA, and cellular proteins, including the heat shock protein Hsp90, the cochaperone p23, and additional, as yet unknown, factors. Functional complexes catalyze the synthesis of a short DNA primer that is templated by epsilon and covalently linked to the terminal protein (TP) domain of P protein. Currently, the only system for generating such complexes in the test tube is in vitro translation of duck hepatitis B virus (DHBV) P protein in rabbit reticulocyte lysate (RRL), which also provides the necessary factors. However, its limited translation capacity precludes a closer analysis of the complex. To overcome this restriction we sought to produce larger amounts of DHBV P protein by expression in Escherichia coli, followed by complex reconstitution in RRL. Because previous attempts to generate full-length P protein in bacteria have failed we investigated whether separate expression of the TP and reverse transcriptase-RNase H (RT-RH) domains would allow higher yields and whether these domains could trans complement each other. Indeed, TP and, after minor C-terminal modifications, also RT-RH could be expressed in substantial amounts, and when added to RRL, they were capable of epsilon-dependent DNA primer synthesis, demonstrating posttranslational activation. This reconstitution system should pave the way for a detailed understanding of the unique hepadnaviral replication initiation mechanism.
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PMID:Reconstitution of a functional duck hepatitis B virus replication initiation complex from separate reverse transcriptase domains expressed in Escherichia coli. 1146 13

Initiation of reverse transcription in hepadnaviruses (hepatitis B viruses) depends on the specific binding of an RNA signal (the packaging signal, epsilon) on the pregenomic RNA template by the viral reverse transcriptase (RT) and is primed by the RT itself (protein priming). We have previously shown that the RT-epsilon interaction and protein priming require the cellular heat shock protein, Hsp90. However, additional host factors required for these reactions remained to be identified. We now report that five cellular chaperone proteins, all known cofactors of Hsp90, were sufficient to reconstitute a duck hepatitis B virus RT active in epsilon binding and protein priming in vitro. Four proteins, Hsp90, Hsp70, Hsp40, and Hop, were required for reconstitution of RT activity, and the fifth protein, p23, further enhanced the kinetics of reconstitution. RT activation by the chaperone proteins is a dynamic process dependent on ATP hydrolysis and the Hsp90 ATPase activity. Thus, our results have defined a minimal complement of host factors necessary and sufficient for RT activation. Furthermore, this defined in vitro reconstitution system has now paved the way for future biochemical and structural studies to elucidate the mechanisms of RT activation and chaperone functions.
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PMID:In vitro reconstitution of functional hepadnavirus reverse transcriptase with cellular chaperone proteins. 1173 92

The dioxin receptor (DR) is a ligand-activated transcription factor that is activated upon binding of dioxins or structurally related forms of xenobiotics. Upon binding ligand the DR translocates from the cytoplasm to the nucleus where it complexes with the partner protein Arnt to form a DNA binding heterodimer, which activates transcription of target genes involved in xenobiotic metabolism. Latency of the DR signaling pathway is maintained by association of the DR with a number of molecular chaperones including the 90-kDa heat shock protein (hsp90), the hepatitis B virus X-associated protein (XAP2), and the 23-kDa heat shock protein (p23). Here we investigated the role of XAP2 in DR signaling and demonstrated that reduced levels of XAP2 labilize the DR, arguing for a function of XAP2 beyond its reported role as a cytoplasmic retention factor. In addition, we showed that a constitutively nuclear DR is degraded in the nucleus and does not require nuclear export for efficient degradation. We also provided evidence implicating the ubiquitin ligase protein C-terminal hsp70-interacting protein (CHIP) in the degradation of the DR, and we demonstrated that this degradation can be overcome by overexpression of XAP2. XAP2 protection of CHIP-mediated degradation is dependent on the tetratricopeptide repeat domain of XAP2 and suggests a mechanism whereby competition for the C-terminal tetratricopeptide repeat acceptor site of hsp90 guides the protein triage decision, the point of determination for either maturation of DR folding or DR degradation.
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PMID:Defining the role for XAP2 in stabilization of the dioxin receptor. 1283 59

Hsp90 is a specialized chaperone that controls the activity of many key regulator proteins such as steroid hormone receptors (SHRs). Hormone binding, and therefore SHR activation, requires Hsp90, which is loaded onto the receptors by a series of events involving Hsp70, Hsp40, Hop, and p23. The reverse transcriptase (RT) of hepatitis B viruses, small DNA-containing viruses that replicate via an RNA intermediate, has been reported to depend similarly on Hsp90 for enzymatic activity. Using an in vitro reconstitution system consisting of recombinant duck hepatitis B virus RT, purified chaperones, and the authentic RNA template Depsilon, we demonstrate here that this RT can be activated efficiently by just Hsp40 and Hsc70 plus energy, without the need for Hsp90 or other cofactors. The reaction appears to proceed selectively with the Hdj1 variant of Hsp40 but not Hdj2 or its yeast homolog Ydj1. The primary reaction product is a metastable, RNA binding-competent intermediate that decays quickly in the absence of its cognate RNA but, in its presence, accumulates in an initiation-competent form over several hours. Because deletion of the RNase H domain rendered the protein partly chaperone-independent, the chaperones may be needed indirectly to relieve occlusion of the RNA binding site by this domain. Our results do not exclude that other factors contribute to RT activation in vivo, but they challenge a fundamental SHR-like dependence on Hsp90. Thus Hsc70, mostly known for its role in general protein folding, is able to effect activation of a highly specialized target protein.
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PMID:Efficient Hsp90-independent in vitro activation by Hsc70 and Hsp40 of duck hepatitis B virus reverse transcriptase, an assumed Hsp90 client protein. 1285 1

To further understand the role that the hepatitis B virus X-associated protein 2 (XAP2) plays in regulating aryl hydrocarbon receptor (AhR) function, a point mutation was introduced at tyrosine 408 of the AhR, changing the residue to an alanine or lysine. These mutations resulted in the loss of AhR binding to endogenous XAP2 in COS-1 cells and reduced binding of exogenously expressed XAP2. Cellular localization of the mutant AhR-yellow fluorescent protein fusion proteins remained nuclear when XAP2 was co-expressed, while the non-mutant receptor was redistributed to the cytoplasm. XAP2 expression caused an overall repression of constitutive and ligand-induced AhR transcriptional activity. However, increased expression of XAP2 had no effect on the AhRY408A mutant transcriptional activity. Additionally the XAP2 binding-deficient AhR mutants showed overall higher transcriptional activity when compared with the non-mutant receptor. Interestingly reduced incorporation of the Hsp90 associated co-chaperone p23 in the unliganded AhR complex was observed with increasing XAP2 expression. The displacement of p23 from Hsp90 did not occur when increasing levels of XAP2 were introduced in COS-1 cells in the absence of the AhR; thus this displacement event occurs specifically within an AhR complex. Finally XAP2 itself was capable of existing in multimeric complexes, and these complexes did not require Hsp90 or AhR to form. However, it is not yet clear whether XAP2 can exist within the AhR complex in more than one copy.
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PMID:The aryl hydrocarbon (Ah) receptor transcriptional regulator hepatitis B virus X-associated protein 2 antagonizes p23 binding to Ah receptor-Hsp90 complexes and is dispensable for receptor function. 1532 22


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