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)

Monoclonal antibodies have been raised against a cell line derived from a dimethylhydrazine-induced rat colon carcinoma. One of these antibodies (MAb E4) has previously been shown to react slightly with normal small intestine and colon, and not with other normal tissues as determined by immunohistochemistry. Using Western immunoblotting we confirmed this tumor specificity. Therefore, the Mr of approx. 66,000 glycosylated antigen (pE4) recognized by MAb E4 appeared to be a potential marker of colon carcinoma. Fifteen human tumor cell lines were tested by flow cytometry for the expression of pE4. This antigen was not detected on these cells. In the rat colon carcinoma cell, pE4 was exclusively found on the cell membrane. pE4 was purified to near homogeneity by immunoaffinity chromatography. The first 20 N-terminal amino acids were identified. Comparison with the NBRF data bank did not reveal a complete homology with known sequenced proteins but similarities were found with the mouse L3T4 precursor, the env polyprotein of human immunodeficiency virus type I, flagellin from Halobacterium halobium and the gp30 from hepatitis B surface antigen. Homology was always found in transmembranous or hydrophobic domains of these proteins. By indirect immunofluorescence analysis of adherent cells and size exclusion chromatography under native conditions, pE4 was found to interact with other molecules and perhaps to be involved in intercellular contact.
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PMID:Characterization, isolation and amino terminal sequencing of a rat colon carcinoma-associated antigen. 201 Feb 33

We tested 1305 female prostitutes from eight areas of the United States for antibodies to human T-cell lymphotropic virus type I/II. Overall, 6.7% were human T-cell lymphotropic virus type I/II seropositive (with antibodies to both gag and env gene products). The seroprevalence rates ranged from 0% in southern Nevada to 25.4% in Newark, NJ. Human T-cell lymphotropic virus type I/II seropositivity was independently associated with race (odds ratio, 4.68), intravenous drug use (odds ratio, 2.94), hepatitis B seropositivity (odds ratio, 2.87), recruitment in Newark (odds ratio, 2.34), and more years of sexual activity (odds ratio, 1.08 per year of sexual activity). Groups with high rates included blacks, Hispanics, and American Indians, and the rates in these groups were significantly higher than among whites and Asian Americans for women both with and without a history of intravenous drug use. Among intravenous drug users, the only other independent associations were more years of sexual activity and recruitment in Newark; and in non-intravenous drug users, hepatitis B seropositivity. These data show that human T-cell lymphotropic virus type I/II infection is present among female prostitutes in some areas of the United States. Further studies are needed to evaluate patterns of transmission and long-term health effects.
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PMID:Seroprevalence and risk factors for HTLV-I/II infection among female prostitutes in the United States. 229 89

One of the open reading frames on hepatitis B virus (HBV) DNA comprises the coding region (designated the env gene) for the virus envelope proteins. Studies on messenger RNA transcription suggest that this gene has the potential to code for three related proteins: (1) a protein of 226 amino acids identified as a major protein constituent of the HBV envelope, termed S-protein; (2) a protein with 55 additional amino acids at the N-terminal coded for by a portion of the env gene upstream of the S-gene (pre-S); (3) a protein corresponding to the entire env gene (pre-S + S). Synthetic peptides from the N-terminals of proteins (2) and (3), and antisera to them have been used to study the occurrence and properties of pre-S sequences. The results presented here provide unambiguous evidence that all three env encoded proteins are present in HBV particles; synthetic peptides corresponding to the gene encoding pre-S are highly immunogenic and can be used in diagnostic tests for detection in human sera of antibodies preferentially recognizing HBV; such antibodies, specific for pre-S determinants, are elicited during hepatitis B infection and by immunization with HBV proteins (2) and (3); the hepatitis B vaccine licensed in the United States does not contain pre-S proteins; and the pre-S proteins of the HBV envelope contain domains specifically recognized by liver cells. These findings suggest that pre-S determinants are important in virus-neutralizing responses and should be present in HBV vaccines.
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PMID:Hepatitis B virus contains pre-S gene-encoded domains. 258 Nov 44

Analysis of deletion and/or site-specific mutants of the hepatitis B virus (HBV) env gene, expressed in human cells, provided clues about the mechanism that retains the L protein, the largest gene product, in a pre-Golgi compartment. Differences in secretability of the analyzed variants suggest that the N-terminal myristic acid and an internal sequence within the PreS1 region function as independent retention signals. N-terminal myristic acid alone neither prevented PreS1 + 2 N-linked glycosylation, which signals cotranslational translocation of the domain, nor strongly inhibited lumenal budding. Thus, myristic acid by itself acts by arresting secretion of lumenal, soluble Env particles. By contrast, the internal retention determinant, mapping in the C-terminal portion of PreS1, also prevented budding. In addition, the presence of this PreS1 segment correlated with the depression of PreS1 + 2 glycosylation. This suggests a connection between L retention and the recently described inhibition of PreS1 + 2 cotranslational translocation. A model can be proposed, according to which HBV surface proteins need to cotranslationally translocate their N-terminal moieties in order to assume a transmembrane topology suitable for particulate assembly and secretion. L protein, whose PreS1 + 2 domain undergoes translocation only posttranslationally, would fail to complete the secretion process. To support this model, we show that forced cotranslational translocation of the PreS1 + 2 domain (by attachment of an N-terminal processed signal sequence) results in secretion of L protein.
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PMID:A C-terminal PreS1 sequence is sufficient to retain hepatitis B virus L protein in 293 cells. 748 79

In addition to their well-recognized hepatotropism, all hepatitis B viruses (HBVs) display marked species specificity, growing poorly or not at all in species other than those closely related to their natural hosts. We have examined the molecular basis for this narrow host range, using duck HBV (DHBV) and heron HBV (HHBV) as a model system. HHBV virions will not infect ducks in vivo and infect cultured duck hepatocytes extremely inefficiently in vitro. Mutant HHBV genomes lacking all viral envelope proteins (HHBV env-) can be complemented in trans with DHBV envelope proteins; the resulting pseudotyped virions can efficiently infect duck hepatocytes. Further complementation analysis reveals that of the two viral surface proteins (L and S), it is the L protein that determines host range. Pseudotyping of HHBV env- with DHBV/HHBV chimeric envelope proteins reveals that replacement of as few as 69 amino acids of the pre-S domain of the HHBV L protein by their DHBV counterparts is sufficient to permit infection of duck hepatocytes. These studies indicate that the species-specificity of hepadnaviral infection is determined at the level of virus entry and is governed by the pre-S domain of the viral L protein.
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PMID:The pre-S domain of the large viral envelope protein determines host range in avian hepatitis B viruses. 760 80

Human recombinant adenoviruses (Ad) have been employed to develop experimental vaccines against a number of infectious agents. Ad-vectored vaccines express recombinant proteins, including any post-translational modifications, into functioning replicas of the native proteins capable of eliciting neutralizing antibodies in both abortive and permissive animal models. Human Ad types 4, 5, and 7 were used to construct recombinant viruses that express the respiratory syncytial virus F or G glycoproteins, the hepatitis B surface antigen, and the HIV env or gag genes. The recombinant Ad-HIV viruses are of particular interest and have been examined for their immunogenicity in dogs and chimpanzees. Dogs were immunized intratracheally with Ad-env recombinants (10(9) pfu/dog). Excellent humoral anti-HIV responses, including neutralizing antibodies, were detected in the sera following booster immunization (12-18 weeks after primary immunization) with a second Ad-env recombinant made in a different Ad serotype (heterotypic booster). Chimpanzees were immunized in two ways, orally with lyophilized virus (10(9) to 10(10) pfu/virus) in enteric-coated capsules or intranasally (10(7) pfu/virus). Intranasal immunization was superior to oral immunization with respect to replication of recombinant viruses as well as induction of anti-Ad and anti-HIV antibodies. Administration by both routes resulted in stimulation of cellular immune responses, as measured by antigen proliferation assays. Anti-HIV antibodies were detected in chimpanzee secretions (salivary, nasal, rectal, vaginal) taken from animals following intranasal immunization with a heterotypic recombinant. Intranasal administration effectively primed chimpanzees to produce high-titred (320-640) serum neutralizing antibodies to HIV following boosting with a baculovirus-derived env (gp160) subunit vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenovirus vectored vaccines. 795 85

According to the current model of hepadnavirus gene expression, the viral envelope proteins are produced from unspliced subgenomic RNAs, in contrast to the retroviral mechanism, where the subgenomic env RNA is generated by RNA splicing. We now describe and characterize a novel duck hepatitis B virus RNA species which is derived from the RNA pregenome by loss of a 1.15 kb intron. This RNA (termed spliced L RNA) codes for the large surface protein (L protein), as does the previously described unspliced mRNA (the preS RNA); however, it differs in 5' leader sequence and promoter control. Mutational analysis indicates that the spliced L RNA is functionally important for virus replication in infected hepatocytes and ducks, but not for virus formation from transfected DNA genomes. This suggests that the newly discovered second pathway for L protein synthesis plays a distinct role in an early step in the viral life cycle.
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PMID:A splice hepadnavirus RNA that is essential for virus replication. 866 64

Intronless mRNAs were classified into two classes based on the sensitivities of their expression to the inhibitory effect of TAgRex, a dominant-negative mutant of the Rex protein of human T cell leukemia virus type I, and their abilities to express the genes encoded in the intron of the human immunodeficiency virus (HIV) genome. Interferon-alpha mRNA could not induce the expression of the env gene of HIV, and its expression was resistant to TAgRex. In contrast, the posttranscriptional regulatory element (PRE), necessary for the nucleo-cytoplasmic export of mRNAs of hepatitis B virus, induced expression of the chloramphenicol acetyl transferase gene located within the intron of the HIV genome. PRE-mediated expression was inhibited by TAgRex. Thus, these results suggest that there are at least two distinct pathways for intronless mRNA expression, one related to and the other unrelated to Rev and Rex functions.
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PMID:Two distinct pathways for intronless mRNA expression: one related, the other unrelated to human immunodeficiency virus Rev and human T cell leukemia virus type I Rex functions. 928 96

Human foamy virus (HFV) is the prototype of the Spumavirus genus of retroviruses. These viruses have a genomic organization close to that of other complex retroviruses but have similarities to hepadnaviruses such as human hepatitis B virus (HBV). Both HFV and HBV express their Pol protein independently of their structural proteins. Retroviruses and hepadnaviruses differ in their requirements for particle assembly and genome packaging. Assembly of retroviral particles containing RNA genomes requires only the Gag structural protein. The Pol protein is not required for capsid assembly, and the Env surface glycoprotein is not required for release of virions from the cell. In contrast, assembly of extracellular HBV particles containing DNA requires core structural protein and polymerase (P protein) for assembly of nucleocapsids and requires surface glycoproteins for release from the cell. We investigated the requirements for synthesis of extracellular HFV particles by constructing mutants with either the pol or env gene deleted. We found that the Pol protein is dispensable for production of extracellular particles containing viral nucleic acid. In the absence of Env, intracellular particles are synthesized but few or no extracellular particles could be detected. Thus, foamy virus assembly is distinct from that of other reverse transcriptase-encoding mammalian viruses.
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PMID:The roles of Pol and Env in the assembly pathway of human foamy virus. 1052 50

DNA vaccines have been demonstrated to be potent in small animals but are less effective in primates. One limiting factor may be inefficient uptake of DNA by cells in situ. In this study, we evaluated whether cellular uptake of DNA was a significant barrier to efficient transfection in vivo and subsequent induction of immune responses. For this purpose, we used the technique of electroporation to facilitate DNA delivery in vivo. This technology was shown to substantially increase delivery of DNA to cells, resulting in increased expression and elevated immune responses. The potency of a weakly immunogenic hepatitis B surface Ag DNA vaccine was increased in mice, as seen by a more rapid onset and higher magnitude of anti-hepatitis B Abs. In addition, the immunogenicity of a potent HIV gag DNA vaccine was increased in mice, as seen by higher Ab titers, a substantial reduction in the dose of DNA required to induce an Ab response, and an increase in CD8+ T cell responses. Finally, Ab responses were enhanced by electroporation against both components of a combination HIV gag and env DNA vaccine in guinea pigs and rabbits. Therefore, cellular uptake of DNA is a significant barrier to transfection in vivo, and electroporation appears able to overcome this barrier.
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PMID:Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. 1077 67


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