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 X protein of hepatitis B virus (HBV) is a transactivator to homologous and heterologous viral and cellular transcriptional regulatory elements. One sequence-specific binding protein, whose binding site located from nt 1102 to nt 1117 of HBV DNA, was identified by mobility shift assay and DNase I foot-printing analysis. A CAT assay experiment demonstrated this 16-bp binding site to have a promoter activity in the X gene transcription. The 58-bp DNA fragment (nt 1085 to nt 1142), which contains the above binding site, could be enhanced by the HBV enhancer. Mobility shift assay using the mutated 58-bp DNA fragments as probes, showed that the mutation, which damaged the palindrome structure between nt 1105 and nt 1112, resulted in loss of the binding activity. This mutation also remarkably reduced the promoter activity. The binding site differed from the target sequences of known transcriptional factors. This factor was thus concluded to be a binding protein to the X gene promoter (X-PBP) of HBV. A homology search demonstrated the binding site to be highly homologous to the promoter elements of human laminin receptor (2H5epitope) and lipoprotein receptor-related protein (LRP) genes.
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PMID:Identification of a binding protein to the X gene promoter region of hepatitis B virus. 144 11

Human hepatitis B virus (HBV) X-gene, previously shown to be capable of trans-activating heterologous regulatory elements of the human beta-interferon gene, the human immunodeficiency virus type I (HIV-1) long terminal repeat (LTR), the simian virus 40 (SV40), and HBV, has the capacity to code for a 17-kDa polypeptide (designated pX17). We now report that pX17 synthesized in Escherichia coli can activate transcription controlled by the HIV-1 LTR using a protoplast fusion technique. Protoplasts of E. coli-containing presynthesized X-protein were fused with lymphocytic H938 cells harboring an integrated copy of a plasmid with the CAT gene under control of the HIV-1 LTR (HIV-1 LTR CAT) and a marked increase in the steady state expression of the CAT mRNA was observed. When the same fused cells were treated with the protein synthesis inhibitor cyclohexamide, the pX17-dependent activation of the HIV-1 LTR was abolished. This result indicates that the X-protein expressed in E. coli is biologically active and suggests that the HBV X-protein-mediated trans-activation of the HIV-1 LTR in this system requires de novo cellular protein synthesis.
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PMID:Transcriptional activation of the human immunodeficiency virus type 1 long terminal repeat by hepatitis B virus X-protein requires de novo protein synthesis. 219

DNA from the pre-S region of the duck hepatitis B virus (DHBV) genome was inserted into an open reading frame vector designed to give high-level expression in Escherichia coli. The resulting fusion protein contained the first 8 amino acids of beta-galactosidase, 86 amino acids of the DHBV pre-S region, and 219 amino acids of chloramphenicol acetyltransferase at the C terminus (beta-gal:pre-S:CAT). Rabbit antiserum against purified beta-gal:pre-S:CAT was used to identify pre-S-containing polypeptides in DHBV particles by Western blotting. A dominant species of 36 kilodaltons (kDa) was identified. Antiserum against the major 17-kDa DHBsAg polypeptide also reacted with the 36-kDa protein. This suggests that the DHBV envelope gene polypeptides share the same carboxyl terminus, but differ in the sites from which translation is initiated. N-linked carbohydrate was not detected on either the 17- or 36-kDa envelope proteins. Anti-beta-gal:pre-S:CAT abolished infectivity of the virus in an in vitro assay. Thus, the pre-S region is exposed on the surfaces of infectious virions and may be directly involved in binding of virus to host-cell receptors.
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PMID:Characterization of a pre-S polypeptide on the surfaces of infectious avian hepadnavirus particles. 243 17

By transfections of hepatitis B virus (HBV) DNA into five human hepatoma cell lines with the characteristics of differentiated human hepatocytes, three human hepatoma cell lines possessing partial hepatocyte-associated markers, and one non-liver cell line, we demonstrated that the expression of hepatitis B surface and core genes preferentially occurred in hepatoma cell lines with differentiated hepatocyte-associated characteristics. With a heterologous CAT gene as a reporter, the transcriptional activity of the promoter region containing both the distal (SPI) and the proximal (SPII) promoters of hepatitis B surface gene was found to show a preference for differentiated hepatoma cell lines. The SPI promoter which produces a RNA transcript for the synthesis of the large surface protein shows a strong preference, at least 750-fold, for differentiated hepatoma cells, while the SPII promoter which produces RNA transcripts for the synthesis of the middle and major surface proteins shows a moderate preference, about 20- to 59-fold. Further study indicates that this 750-fold preference of the SPI transcriptional activity for differentiated hepatoma cell lines can be attributed to the regulatory sequences of both the SPI and the HBV enhancer regions. These results also imply the important role of the large surface protein of HBV on the hepatocyte-specific infectivity of this virus.
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PMID:The surface gene promoter of the human hepatitis B virus displays a preference for differentiated hepatocytes. 254 37

The genome of hepatitis B virus (HBV) contains an enhancer element located in the coding region of the DNA polymerase open reading frame between the 3' end of the S gene and the X gene. To determine whether HBV enhancer is species and/or tissue specific, several cell lines were transfected with CAT plasmids containing different subgenomic fragments of the HBV genome. The activity of the HBV transcriptional enhancer sequence was shown not to be strictly hepatotropic, since it was found in hematopoietic tissues. This activity was not species specific either, since it was found in feline and mouse cells.
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PMID:Broad specificity of the hepatitis B enhancer function. 282 Jan 33

The ability of hepatitis B virus (HBV) to stimulate the expression of a cellular gene was investigated by using a transient-expression system. A plasmid in which the expression of the bacterial chloramphenicol acetyltransferase (cat) gene had been placed under the control of the DNA sequences that regulate the expression of the human beta-interferon gene was constructed. In Vero cells, cotransfection of the 2.7-kilobase BglII DNA fragment of HBV together with the test plasmid containing the cat gene resulted in stimulation of the expression of the cat gene. This HBV DNA fragment was specific in its trans-activation; no significant stimulation of CAT activity was observed in constructs when the promoter and enhancer elements were derived from the murine sarcoma viral long terminal repeat, Rous sarcoma virus, BK virus, or simian virus 40. Results of subcloning of the HBV DNA fragment indicate that the trans-activating function resides in a 944-base-pair EcoRV-BglII DNA fragment of the HBV genome that contains the X structural gene and its promoter element. Removal of the promoter from the X structural gene resulted in loss of the trans-activating function. A frameshift mutation within the X gene region also eliminated the trans-activating activity. These results suggest that the X antigen could play a role in HBV infections by activating the expression of cellular genes.
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PMID:Transcriptional trans-activating function of hepatitis B virus. 282 53

Recently we have shown that the hepatitis B virus (HBV) X gene encodes a transactivating factor. Here we report on the construction of a series of HBx expression plasmids which were tested for a transactivating function by cotransfections with a plasmid expressing the CAT gene under control of the SV40 early promoter. One of the plasmids, expressing a HBx specific protein, is shown to transiently transactivate CAT gene expression after cotransfection into the human cell line CC113. Furthermore, a cloned integrated HBV DNA sequence is also shown to transactivate several viral promoters and LTRs. By sequence analyses we can demonstrate that only the HBx ORF is intact and that it is fused to an ORF of at least 228 bp in the flanking cellular DNA. The HBx gene is cotranscribed with the flanking cellular DNA, resulting in a RNA of approximately 10 kb. By subcloning of the integrate we can demonstrate that the presence of the HBx gene and its expression by the HBV enhancer and/or the HBx promoter is required for the transactivating function of the integrated HBV DNA.
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PMID:A transactivating function encoded in the hepatitis B virus X gene is conserved in the integrated state. 285 54

The X protein of hepatitis B virus is known to be a trans-activator of viral and cellular genes and to be a serine protease inhibitor as well. X protein has no DNA-binding activity, but is postulated to exert its trans-activation function by interacting with cellular proteins. To investigate interaction sites of X protein with cellular proteins, we carried out an immunoprecipitation inhibition assay using several different anti-X antibodies in the presence or absence of cellular proteins. Results elucidated three separate sites (aa 65-72, aa 105-115, and aa 131-142; U22, X1, and Z44 sites, respectively) of the X protein that cooperatively interacted with cellular proteins. Analyses with a series of mutant X proteins also supported the interactions at the U22, X1, and Z44 sites. Based on the CAT activity assay, the essential regions for the trans-activation function of X protein overlapped with these three interaction sites. Furthermore, these interaction sites also coincide with the structures necessary for the serine protease inhibitor activity. Thus, the trans-activation function and serine protease inhibitor activity of X protein may be exerted by interaction with cellular proteins through at least these three sites.
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PMID:Three sites of the hepatitis B virus X protein cooperatively interact with cellular proteins. 797 52

A panel of mutants of the hepatitis B virus X gene (HBx) was constructed by oligonucleotide-directed insertion of two codons (Arg Pro) at 10- or 20-amino-acid intervals along the entire gene. These mutants were tested in transiently transfected HepG2 cells for their effects on HBx trans-activation of an AP1-CAT reporter plasmid. The effects of HBx mutations on the mRNA and protein stability were also determined. Our results reveal two separate internal domains of the HBx, one around amino acid residue 68 and the other between residues 110 and 139, that are necessary for its activity. Mutations in the amino terminus (to position 45), between the two necessary domains and in the extreme carboxyl terminal portion of HBx, have little or no effect on its activity.
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PMID:Two-codon insertion mutations of the HBx define two separate regions necessary for its trans-activation function. 824 76

The expression of the cellular gene coding for the epidermal growth factor (EGF) receptor (EGF-R) was assayed in the presence of hepatitis B virus (HBV) gene expression under different experimental conditions in human hepatoma-derived cells. First, transfection experiments of the well-differentiated HepG2 human hepatoma cell line using different expression vectors of the HBV X-region demonstrated that the X-gene product is capable of inducing EGF-R gene overexpression; in addition, by using a stable in vitro expression system for HBV, it was shown that EGF-R gene expression in these cells is greater than in the uninfected parent cells, and that this results in a three-fold increase in 125I-EGF binding. Finally, a CAT-expression assay was performed, indicating that regulatory regions of the EGF-R-gene are target sequences for X-protein trans-activation.
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PMID:Trans-activation of epidermal growth factor receptor gene by the hepatitis B virus X-gene product. 839 16


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