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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The N-terminal 54 base pairs (encoding amino acid residues 2-19) within the preS1 region of the human hepatitis B virus surface antigen gene were deleted by site-directed mutagenesis. Unlike the wild type large surface antigen protein, when this mutated gene was expressed in monkey kidney cell line COS-M6, the protein product (S301 protein) could be secreted from the cells. Moreover, the inhibition of the secretion of the major surface antigen protein by this altered large surface antigen protein was greatly reduced, suggesting that the deleted region contained a retention sequence which prevented the secretion of the large surface antigen. However, the coexpression of the major S protein was essential for the secretion of the S301 protein. When coexpressed, the secretion of these two proteins was synchronous. Like the wild type large surface antigen protein, the S301 protein could be translocated into endoplasmic reticulum and glycosylated after its synthesis in COS cells. The S301 protein was thermostable and proteinase-resistant. It also retained the antigenicity of the large S and major S proteins. Given the fact that the S301 protein is readily secretable, stable and identical to the large S protein in terms of their antigenicity, it may be developed into a new generation of recombinant vaccine for the prevention of viral hepatitis.
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PMID:An HBV large surface antigen protein which can be secreted from mammalian cells. 159 Sep 20

Unlike many other reverse transcriptase genes, the polymerase (P) gene of the hepatitis B viruses is expressed by translational initiation from its own AUG codon rather than by ribosomal frameshifting during translation of the overlapping core gene (C). To explore the mechanism of its translation, we have fused the P gene of duck hepatitis B virus to the bacterial lacZ gene at a point 3' to the C-P overlap; this allows detection of the products of P translation with antisera to the lacZ-encoded protein. The C and P/Z coding regions were cloned downstream of a heterologous promoter and expressed in COS-7 cells. A single, bicistronic mRNA containing both C and P sequences is detected in these cells, and translational initiation occurs efficiently at the internally situated P AUG. Mutations affecting C translation have only minimal effects on P expression, in contrast to what would be expected from a modified scanning model for translation. We conclude that P translation depends on a mechanism other than scanning to allow internal entry of ribosomes to the region of the P initiator.
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PMID:Mechanism of translation of the hepadnaviral polymerase (P) gene. 169 11

Aminoterminal deletion mutants of the gene encoding the large hepatitis B surface protein were expressed in COS cells using a new expression vector. The truncated protein showed the same intracellular retention like the wild type protein. The findings show that the secretion block of the protein is not due to its aminoterminal myristylation.
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PMID:Expression of large hepatitis B envelope protein mutants using a new expression vector. 173 99

A large surface protein of human hepatitis B virus was expressed from a mutated S gene in which both the reported retention sequence (aa 2-19) and the C-terminal half of the preS1 region (aa 66-117) were deleted. This retention sequence-free protein was not secreted from the monkey kidney cell line COS-M6 in transient expression assays. When this large S protein was overexpressed in the presence of the major S protein, the secretion of the latter was severely inhibited. Moreover, the presence of S protein in large abundance did not facilitate the secretion of the mutated large S protein at all, indicating that it was subject to more profound retention than the wild-type large S protein. The findings that, like the wild-type large S protein, this altered protein retained some of the properties of its C-terminal S domain, and that the preS1 region was still on its surface suggested that there was no extensive alteration of the polypeptide folding. The interpretation is favored that the C-terminal half of the preS1 region plays a crucial role in the secretion of the large S protein when its N-terminal retention sequence is not present.
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PMID:The C-terminal half of the preS1 region is essential for the secretion of human hepatitis B virus large S protein devoid of the N-terminal retention sequence. 199 88

Hepatitis B virus core antigen gene expresses two cocarboxy-terminal proteins, termed precore and core proteins. Both precore and core proteins can form nucleocapsid-like particles. In order to understand the mechanism that leads to the formation of the nucleocapsid, we have expressed precore and core protein sequences in COS cells, a monkey kidney cell line, and compared the properties of these two particles. Our results show that core protein can form particles with various densities and they are present mostly in the cytosol. Precore protein, on the other hand, forms particles with one predominant density, and a majority of these particles are present in the lumen of the endoplasmic reticulum (ER). Furthermore, our results show that, when coexpressed in the same cells, core protein and the ER-associated surface antigens (envelope protein) show colocalization, indicating interaction between these two viral structural proteins.
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PMID:Comparative studies of hepatitis B virus precore and core particles. 240 5

We have used the chloramphenicol acetyltransferase (cat) gene expression system to study the effect of the X protein of hepatitis B virus (HBV) on viral enhancers. Plasmids containing the HBV enhancer and the core gene promoter linked to the cat gene were cotransfected with a plasmid containing the X gene into the human hepatoma cell line PLC/PRF/5. Our results indicate that the transfected X gene caused a trans-activation of the HBV enhancer. If a frameshift mutation or a deletion in the X structural gene was created, this trans-activation function was abolished. This result and the observation that the frameshift mutation did not alter the transcription of X mRNA suggest that the X protein is the trans-activating factor. Using similar techniques, we found that the X protein was also capable of trans-activating the simian virus 40 (SV40) and Rous sarcoma virus enhancers (pSV2cat and pRSVcat) in CV-1 cells. However, trans-activation of the SV40 enhancer by the X protein was not observed in COS-1 cells. By cotransfecting pSV2cat and the X gene with a plasmid containing either the intact SV40 genome, the SV40 genome devoid of the T-antigen (T-ag) gene, or only the T-ag gene, we demonstrated that SV40 T-ag can suppress trans-activation by the X protein. SV40 T-ag did not inhibit expression of the X gene or inactivate the X protein. The most probable mechanism of this inhibition is that T-ag competes with the X protein for a common target.
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PMID:trans-activation of viral enhancers by the hepatitis B virus X protein. 282 5

A recombinant plasmid consisting of (i) the entire genome of hepatitis B virus (HBV) DNA, (ii) the replication origin of SV40 virus, and (iii) a deletion derivative of pBR322 was introduced either into COS cells of monkey origin which constitutively express SV40 large T antigen, or into thymidine kinase(TK)-deficient mouse L cells together with the TK DNA of Herpes simplex virus. In the COS cell system, the transfecting recombinant DNA replicates via SV40 origin and is maintained in an autonomously replicating state. The cells carrying these extrachromosomal elements express the hepatitis B surface antigen gene at moderate rate, and release the products into the culture medium. However, neither core antigen nor e antigen expression was detected in this system. In the L cell system, the transformed L cells carry the recombinant DNA in a chromosomally integrated state. Such cells express the surface antigen gene at high rate, and release the products into the culture medium. This system also excretes the e antigen into the culture medium. The core antigen was not detected.
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PMID:Two mammalian cell systems for propagation of the hepatitis B virus genome in extrachromosomal and chromosomally integrated states: production of the surface and e antigens. 299 49

The preS/S coding region of hepatitis B virus encodes two polypeptides (preS1 and preS2) that are larger in size but less abundant than the major viral surface antigen (S) protein. Unlike the preS2 and S proteins, the preS1 protein is preferentially localized on circulating virus particles but is not efficiently secreted from mammalian cells in culture. To search for differences in protein processing that might relate to these properties, we determined whether any of the hepatitis B virus surface proteins are acylated with long-chain fatty acids. Transfected COS cells expressing all three proteins were incubated with 3H-palmitate or 3H-myristate, and the cell extracts were examined by immunoprecipitation. While none of these proteins was labeled with 3H-palmitate, the preS1 protein but not the preS2 or S protein incorporated 3H-myristate via a hydroxylamine-resistant amide linkage. Comparison of the N-terminal amino acid sequences of hepadnaviral preS1 proteins with those of known myristylated proteins suggests that this unusual modification may be a common feature of all hepadnaviral preS1 proteins.
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PMID:The preS1 protein of hepatitis B virus is acylated at its amino terminus with myristic acid. 357 47

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.
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PMID:Expression of hepatitis B virus surface antigen gene in cultured cells by using recombinant plasmid vectors. 629 4

We have constructed two simian virus 40 early replacement recombinants that have the coding sequences for hepatitis B virus surface antigen (HBsAg). One construction, LSV-HBsAg, has the coding region for HBsAg but not the portion encoding the putative pre-surface antigen leader. Transformed monkey kidney cells (COS) infected with this recombinant express large quantities of the characteristic partially glycosylated HBsAg molecule, which are assembled into 22-nm particles that appear similar to those produced by human liver cells infected with hepatitis B virus. This result indicates that the pre-surface antigen sequences are not required for the synthesis of HBsAg or its assembly into particulate structures. The second recombinant, LSV-HBpresAg, has the entire surface antigen gene, including the putative promoter and pre-surface antigen region. COS cells infected with this recombinant plasmid produce 40- to 50-fold less HBsAg than those infected with the LSV-HBsAg recombinant plasmid. RNA mapping studies suggest that the transcription of the HBsAg gene is initiated at more than one site, or alternatively, that RNA splicing of transcripts occurs in the pre-surface antigen region.
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PMID:Synthesis of hepatitis B surface antigen in mammalian cells: expression of the entire gene and the coding region. 631 Jan 47


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