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)

A new hepatitis B virus (HBV) transcript of about 2.2 kilobases was identified in HBV DNA-transfected human hepatoma cells. The 5' terminus of this viral RNA appears to map at one or more of the precore initiation sites, contains a deletion of 1,223 bases corresponding to the last codon of the core gene to the middle of the surface antigen gene, and terminates at the 3' polyadenylation site used by the other known HBV RNAs. The junction region of the deleted sequences showed the conserved splice donor and acceptor GT-AG sequences. Moreover, when a mutant HBV DNA in which the splice acceptor site was changed from AG to CG was transfected into human hepatoma cells, no 2.2-kilobase RNA was detected, further suggesting that this RNA represents a spliced transcript. The core gene, although an amino acid shorter, still encoded a functional viral core protein in complementation experiments. Sequence analysis of the cDNA of the 2.2-kilobase RNA suggests that this transcript can potentially encode a new protein that comprises the reverse transcriptase domain of HBV. However, genetic analysis using a transient DNA transfection system suggests that the gene product(s) of this transcript is not essential for viral replication. The function of this transcript remains to be studied.
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PMID:Hepatitis B virus transcript produced by RNA splicing. 276 Sep 87

To determine whether hepatitis B virus (HBV) regulates the expression of the human beta-interferon gene, a series of recombinant bovine papilloma virus plasmids containing the human interferon gene and various fragments of the HBV genome were constructed and used to transform C127 cells, a murine fibroblast line. Analysis of the DNA from transformed C127 cells indicated that the interferon gene was intact and that the plasmids replicated as stable multicopy elements. The 1828-base-pair BamHI HBV DNA fragment containing the core antigen gene, but not the 2755-base-pair Bgl II HBV DNA fragment encoding both the surface antigen and the X antigen, suppressed the production of human beta-interferon. No effect by any of the recombinant plasmids on the synthesis of murine interferon was detected. The suppression of human beta-interferon by HBV occurs via a trans-acting factor. A frameshift mutation within the HBV core gene alleviates the inhibitory activity; thus we infer that the core protein is this factor or is crucially associated with this activity.
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PMID:Hepatitis B virus suppresses expression of human beta-interferon. 282 71

A peptide corresponding to the major immunogenic site of the protein VP1 of foot-and-mouth disease virus (FMDV) will elicit a protective neutralizing antibody response in guinea-pigs, cattle and pigs. The response is much greater when the peptide is presented as a linear dimer or tetramer and pigs receiving as little as 40 micrograms peptide have been protected against challenge infection. An even greater response is obtained when the peptide is presented as part of the core protein of hepatitis B virus. Moreover, responsiveness to the peptide in non-responder mice can be stimulated by the simultaneous inoculation of an appropriate T-cell epitope linked to the FMDV peptide.
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PMID:Use of peptides for immunization against foot-and-mouth disease. 283 87

We have chemically synthesized a DNA duplex of 560 nucleotides that codes for the hepatitis B virus (HBV) core protein. The synthetic gene contains 27 unique internal restriction sites. Thereby, it can easily be mutagenized by replacement of rather short restriction fragments. A number of restriction recognition sequences are in common between the synthetic and the authentic gene, thus allowing for the transfer of synthetic segments into the cloned viral genome. Several unexpected mutations in the synthetic gene were readily corrected utilizing the multiple unique restriction sites. In Escherichia coli, the expression level of the synthetic gene product amounts to about 4% of the total soluble protein. It forms particles closely resembling native HBV cores. After transfer of the synthetic gene into the viral genome, transient expression in a hepatoma cell line yields proteins indistinguishable from the native gene products. The synthetic gene thus provides a useful tool for studies on the structure and function of the isolated HBV core protein as well as the gene and its various products in the viral life-cycle.
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PMID:Total chemical synthesis of a gene for hepatitis B virus core protein and its functional characterization. 290 97

Human T-cell lymphotropic viruses designated HTLV III or LAV are considered to represent the causative agent(s) of the acquired immunodeficiency syndrome (AIDS). Individuals who have been infected with these viruses may generally be identified on the basis of a positive serological test for antibodies against the protein components of these viruses. Purified viruses or viral proteins have been utilized for developing such tests. Since AIDS may be transmitted by blood transfusion and by blood products, screening of donors for antibodies to HTLV III/LAV has become a necessity. Such screening may be facilitated by the application of assays based on the use of crude virus-infected tissue culture media avoiding elaborate, expensive and potentially hazardous virus purification steps. Serum specimens were mixed with an appropriate dilution of an HTLV III-infected tissue culture-derived fraction, obtained by precipitation with polyethylene glycol 6000 and treatment with Tween 80 and tri-n-butylphosphate (to disrupt virus particles), and incubated with polystyrene beads coated with antibodies to HTLV III/LAV (anti-HTLV III). Subsequently, washed beads were incubated with either 125I- or beta-lactamase-labeled anti-HTLV III. The radioactivity or enzymatic activity associated with the beads was proportionate to the quantity of HTLV III antigen originally added to the beads. The presence of anti-HTLV III in serum specimens resulted in decreased antigen binding and thus in decreased radioactivity or diminished beta-lactamase activity associated with the beads. The test was specific for antibodies to the approximately equal to 24 kDa core protein of HTLV III. The prevalence of these antibodies (given in parentheses) in distinct populations was as follows: random blood donors (0.33%); hemophiliacs (36.4%); random homosexual males (25.1%); homosexual males preselected on the basis of positive markers for infection with hepatitis B virus (50%); and those with persistent lymphadenopathy (70%).
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PMID:Radioimmunoassay and enzyme-linked immunoassay of antibodies to the core protein (P24) of human T-lymphotropic virus (HTLV III). 298 12

A new series of double-selection plasmids containing recombinant genes expressing the neomycin phosphotransferase (NEO) of transposon Tn5 and mouse dihydrofolate reductase (DHFR) in mammalian cells is described. Activity of the recombinant DHFR gene varied more than 50-fold, depending on the location of the simian virus 40 72 base-pair repeat or enhancer, which is part of the promoter of the NEO unit. A NEO-DHFR module with the enhancer located at the 3' end of the DHFR gene was inserted into a plasmid containing four tandem head-to-tail copies of the hepatitis B virus (HBV) genome and the new plasmid was used to transform DHFR- Chinese hamster ovary cells. In one of the cell lines obtained, an unrearranged copy of the HBV tetramer could be amplified 300-fold by increasing selective pressure with methotrexate, resulting in a proportional increase of the synthesis of HBV surface antigen. Four different mRNAs detected in the amplified cell line probably encode HBV core protein, pre-S and surface antigens, and the X protein. As a result of the DNA amplification, synthesis of HBV proteins is no longer restricted to resting cells. Integrated plasmid sequences appear to be stable during the amplification process.
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PMID:A recombinant Chinese hamster ovary cell line containing a 300-fold amplified tetramer of the hepatitis B genome together with a double selection marker expresses high levels of viral protein. 302 26

Using recombinant DNA methods, many different approaches may be followed to optimize immunoprophylaxis against hepatitis B viruses. Most obviously a future vaccine should contain besides the known major surface protein two further envelope proteins which have recently been identified. All three envelope proteins should be present on the same particle in natural proportion and conformation. Such a vaccine may induce a more reliable and more durable immune protection even in difficult cases. The protective potential of the viral core protein, in particular of HBeAg, ought to be studied further experimentally. Possibly, the core proteins may be helpful in an immune therapy of already infected persons.
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PMID:[Approaches to developing an optimal vaccine against hepatitis B viruses]. 306 27

Using synthetic hepatitis B virus (HBV) mRNAs, we have shown that expression of HBV core-antigen gene sequences in Xenopus oocytes leads to the stable accumulation of 21-kDa cytoplasmic core protein (P21). In contrast, expression of precore plus core sequences leads mainly to the secretion of a heterogeneous population of proteins ranging in size from 15 to 22 kDa that collectively display viral e antigen (HBeAg) activity. We demonstrate that the precore region contains a cleavable 19 amino acid signal peptide that targets the precore proteins to the secretory pathway. The initial product of translocation (P22) is further processed during migration through the secretory pathway, apparently by a series of cleavage events at the arginine-rich carboxyl terminus, to yield multiple proteins of 15-18 kDa (P15-P18) that are secreted along with some P22. Our results indicate that serum HBeAg is generated by a signal peptide-mediated secretion event dependent on precore sequences.
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PMID:A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of a heterogeneous population of e antigens in Xenopus oocytes. 318 31

We have examined the expression of duck hepatitis B virus (DHBV)-associated proteins in experimentally infected ducks by an immunoblot (Western) method. The DHBV-related core protein, C protein, was identified at the position of 35,000 Da (P35). Pre-S proteins were recognized as two major bands (P37 and P28), the former representing pre-S1 and the latter pre-S2 protein. Expression of the proteins was examined in the early phase of infection in ducklings sequentially sacrificed from 6 hr postinoculation to 10 days. C protein (P35) was detected as early as 24 hr postinoculation. This timing coincided with the exponential increase of RNA transcripts and double-stranded viral DNA. Pre-S1/S2 proteins were detected at 3 days postinoculation. The early appearance of C protein suggested that the proteins were utilized for nucleic acid packaging. On the other hand, the late appearance of pre-S1/S2 proteins suggested that they were utilized in the production of virions near the end of the replication cycle.
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PMID:Expression of pre-S1, pre-S2, and C proteins in duck hepatitis B virus infection. 318

The major hepatitis B virus (HBV) core protein is a viral structural protein involved in nucleic acid binding. Its coding sequence contains an extension of 29 codons (the "precore" region) at the amino terminus of the protein which is present in a fraction of the viral transcripts. This region is evolutionarily conserved among mammalian and avian HBVs, suggesting it has functional importance, although at least for duck HBV it has been shown to be nonessential for replication of infectious virions. Using in vitro assays for protein translocation across the endoplasmic reticulum membrane, we found that the precore region of the HBV genome encodes a signal sequence. This signal sequence was recognized by signal recognition particle, which targeted the nascent precore protein to the endoplasmic reticulum membrane with efficiencies comparable to those of other mammalian secretory proteins. A 19-amino acid signal peptide was removed by signal peptidase on the lumenal side of the microsomal membrane, generating a protein similar to the HBV major core protein, but containing 10 additional amino acids from the precore region at its amino terminus. Surprisingly, we found that 70-80% of this signal peptidase-cleaved product was localized on the cytoplasmic side of the microsomal vesicles and was not associated with the membranes. We conclude that translocation was aborted by an unknown mechanism, then the protein disengaged from the translocation machinery and was released back into the cytoplasm. Thus, a cytoplasmically disposed protein was created whose amino terminus resulted from signal peptidase cleavage. The remaining 20-30% appeared to be completely translocated into the lumen of the microsomes. A deletion mutant lacking the carboxy-terminal nucleic acid binding domain of the precore protein was similarly partitioned between the lumen of the microsomes and the cytoplasmic compartment, indicating that this highly charged domain is not responsible for the aborted translocation. We discuss the implications of our findings for the protein translocation process and suggest a possible role in the virus life cycle.
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PMID:Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. 328 45


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