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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunodominant B and T cell epitopes have been demonstrated recently on the preS1 and PreS2 regions of the hepatitis B virus (HBV) envelope protein. Synthetic peptide analogs corresponding to the preS2 region elicit virus-neutralizing antibodies and protect chimpanzees against HBV infection. Antibodies raised by immunization with peptides derived from the preS1 sequence block the site involved in HBV attachment to cell receptors, and are expected to be virus-neutralizing. Results presented here show that antisera raised against synthetic peptide analogs carrying the immunodominant epitope of the preS1 and preS2 sequence, respectively, and corresponding to two HBV subtypes, adw2 and ayw, each recognized preS1 and preS2 specific epitopes on all serological subtypes of the HBV envelope protein. Thus, the sequence variability within the preS1 and preS2 regions does not represent an impediment to the development of synthetic peptide or genetically engineered hepatitis B preS immunogens for worldwide immunization.
Mol Immunol 1987 Sep
PMID:Antibodies to synthetic peptides from the pre-S1 and pre-S2 regions of one subtype of the hepatitis B virus (HBV) envelope protein recognize all HBV subtypes. 365 11

To investigate the mechanism by which complex membrane proteins achieve their correct transmembrane orientation, we examined in detail the hepatitis B surface antigen for sequences which determine its membrane topology. The results demonstrated the presence of at least two kinds of topogenic elements: an N-terminal uncleaved signal sequence and an internal element containing both signal and stop-transfer function. Fusion of reporter groups to either end of the protein suggested that both termini are translocated across the membrane bilayer. We propose that this topology is generated by the conjoint action of both elements and involves a specifically oriented membrane insertion event mediated by the internal sequence. The functional properties of each element can be instructively compared with those of simpler membrane proteins and may provide insight into the generation of other complex protein topologies.
Mol Cell Biol 1987 Oct
PMID:Multiple topogenic sequences determine the transmembrane orientation of the hepatitis B surface antigen. 368 95

Antibody responses to the three envelope (env) proteins of hepatitis B viral particles (HB-VP): the S-encoded P25 polypeptide; the pre-S(2)- and S-encoded GP33/GP36 polypeptide; and the large entire env gene (pre-S + S) product, P39/GP42, were investigated using a Western immunoblotting assay (WIBA). HB-VP proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose by electroblotting were used as antigenic probes to determine the polypeptide specificity of these antibodies present in immune individuals. Antisera from human subjects either after a natural HBV infection or after active immunization with the hepatitis B vaccine licensed in France were selected on the basis of a positive serological RIA test for antibodies against hepatitis B surface antigen (HBsAg). In all studied cases, the lack of reactivity of the anti-HBs/P25 antibodies in blots from reduced SDS gels confirms that the S-related-determinants have a conformation sensitive to denaturing agents. In contrast, the anti-pre-S(2)/GP33-GP36 antibodies and the anti-pre-S(1)/P39-GP42 antibodies can be easily detected in WIBA, providing these antibodies recognize the disulfide-bond independent pre-S determinants on the denatured env proteins. However, antisera raised in guinea-pigs against individual HBsAg polypeptides contain antibodies reacting with denatured S-proteins, suggesting that the sequential S-determinants are lost during HBV morphogenesis. Antibody responses in HBV convalescing patients or vaccinated healthy donors are shown to be characterized by: an early transient polypeptide specific-antibody response to pre-S(2)-sequences (detected in WIBA); a persistent antibody response to conformation-dependent S-determinants (detected in RIA). This implies that effective long-term protection against HBV infection requires antibodies directed to native env proteins.
Mol Immunol 1986 May
PMID:Immunochemical structure of the hepatitis B surface antigen vaccine--II. Analysis of antibody responses in human sera against the envelope proteins. 374 12

We constructed a plasmid coexpression vector that directs the insertion of a foreign gene of interest together with the Escherichia coli beta-galactosidase (beta gal) gene into the thymidine kinase (TK) locus of the vaccinia virus genome. Tissue culture cells that had been infected with vaccinia virus were transfected with a plasmid vector containing a foreign gene. TK- recombinants could be selected by a plaque assay on TK- cells in the presence of 5-bromodeoxyuridine and distinguished from spontaneous TK- mutants by the addition of a beta-gal indicator to the agarose overlay. Plaques that expressed beta-gal stained dark blue within several hours at 37 degrees C. Alternatively, TK- selection could be eliminated, and recombinant plaques could be readily identified solely by their blue color. The reverse procedure, in which the starting virus expresses beta-gal (i.e., forms blue plaques) and the desired recombinant has deleted the entire beta-gal gene (i.e., forms white plaques), is another alternative. Each protocol was tested by constructing vaccinia virus recombinants that express hepatitis B virus surface antigen.
Mol Cell Biol 1985 Dec
PMID:Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. 393 16

We have developed a highly efficient system for producing hepatitis B virus surface antigen in cultured mammalian cells. This system utilizes a recombinant bovine papilloma virus in which the hepatitis surface antigen coding sequences are inserted into the 5' untranslated region of the mouse metallothionein-I gene. Mouse fibroblasts stably transformed with this molecule produce surface antigen at levels as high as 10 mg/L/24 h and can be maintained in continuous culture for up to 85 days.
J Mol Appl Genet 1984
PMID:Efficient production of hepatitis B surface antigen using a bovine papilloma virus-metallothionein vector. 609 May 67

Thymectomised and irradiated DBA/2 mice were injected intraperitoneally with human serum containing high titer of HBsAg, and were positive for HBsAg. Through the entire experiment neither degenerative and inflammatory lesions nor hepatitis B virus antigens could be detected in the liver of these animals by histomorphology and immunofluorescence, respectively. The sera of all these mice were negative for HBsAg by radioimmunoassay. By electron microscopy, however, increasing amounts of filaments and round particles measuring 20-22 nm in diameter could be observed in the endoplasmic reticulum of the mouse hepatocytes from the 8th day following injection. From the 90th day after inoculation the number of the filaments increased in an extreme degree. After fixation with KMnO4 and EDTA preferential staining, the filaments proved to be highly electrondense. According to the authors the filaments observed in mouse livers are lipoproteins produced by the hepatocytes in response to HBV inoculation. The appearance of the filaments is HBsAg-like, though their immunological characteristics become modified.
Virchows Arch B Cell Pathol Incl Mol Pathol 1982 Aug
PMID:HBsAg-like structures in immunosuppressed mice inoculated with human hepatitis B virus. 612 39

A computerized method for predicting the locations of protein antigenic determinants is presented, which requires only the amino acid sequence of a protein, and no other information. This procedure has been used to predict the major antigenic determinant of the hepatitis B surface antigen, as well as antigenic sites on a series of test proteins of known antigenic structure [Hopp & Woods (1981) Proc. natn. Acad. Sci. U.S.A. 78, 3824-3828.] The method is suitable for use in smaller personal computers, and is written in the BASIC language, in order to make it available to investigators with limited computer experience and/or resources. A means of locating multiple antigenic sites on a homologous series of proteins is demonstrated using the influenza hemagglutinin as an example.
Mol Immunol 1983 Apr
PMID:A computer program for predicting protein antigenic determinants. 619 Dec 10

The entire hepatitis B virus (HBV) genome and its fragments have been cloned into the BamHI site of the plasmid pBR322 vector. The identity of physical maps of cloned and authentic virion DNAs was demonstrated by restriction enzyme analysis. The location of restriction sites is suggestive of a certain similarity between the studied HBV DNA and HBV DNA, subtype ayw (Galibert et al., 1979). From the restriction enzyme analysis of virion DNA repaired and 32P-labeled by the endogenous DNA-polymerase reaction, the new information concerning the location and maximal length (approximately 1500 nucleotides) of the single-stranded region of HBV DNA has been established.
Mol Biol (Mosk)
PMID:[The comparative mapping of virion and cloned DNA of the hepatitis B virus]. 629 66

By using a new host-vector system, expression of the gene coding for hepatitis B surface antigen has been studied. A subgenomic fragment of cloned hepatitis B viral DNA was inserted into the plasmid vector pSV010. Transfection of COS cells with the recombinant plasmid vector containing hepatitis sequences leads to the synthesis of hepatitis B surface antigen, which is released in the culture medium in the form of 22-nm particles similar to those found in the sera of hepatitis carriers.
Mol Cell Biol 1983 Jan
PMID:Expression of hepatitis B virus surface antigen gene in cultured cells by using recombinant plasmid vectors. 629 4

We introduced the gene encoding the hepatitis B virus surface antigen (HBsAg) into simian virus 40 (SV40)-based plasmids capable of autonomously replicating in both Escherichia coli and permissive monkey cells. After introduction into monkey cells by transfection, these plasmids directed the synthesis of high levels of HBsAg, as determined by immunofluorescence, radioimmunoassays, and identification by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the polypeptides comprising the antigen. Expression was dependent upon the presence of an SV40 promoter, with both the early and late promoters able to effectively initiate transcription. Using expression of HBsAg to assay promoter function, we demonstrated that an intact copy of the SV40 72-base pair repeat, which constitutes an essential element of the SV40 early promoter during the lytic SV40 cycle and which can enhance the transcriptional activity of heterologous promoters, was not required for HBsAg expression, suggesting that the hepatitis genome contains an enhancer element capable of complementing that provided by the 72-base pair repeat element of SV40. The antigen appears to be glycosylated after synthesis in transfected cells and is apparently secreted, as evidenced by the localization of [35S]cysteine-labeled antigen to the medium of transfected cultures. Using constructions in which the first ATG sequence appearing in HBsAg mRNA was that corresponding to the gene encoding the mature form of the antigen, we demonstrated that these post-translational events could occur without the involvement of a putative precursor peptide suggested by the DNA sequence of the viral genome. In view of the inability of hepatitis B virus to propagate in vitro, this strategy offers a convenient approach for further characterizing the biosynthesis of this antigen and may provide a means to identify additional polypeptides encoded by this virus.
Mol Cell Biol 1983 Jan
PMID:Plasmid-directed synthesis of hepatitis B surface antigen in monkey cells. 629 7


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