Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatitis B virus X protein stimulates transcription from a variety of promoter elements, including those activated by transcription factor NF-kappa B. A diverse group of extra- and intracellular agents, including growth factors and the human immunodeficiency virus tat protein, have been shown to require a functional protein kinase C (PKC) system to achieve activation of NF-kappa B. In this study we have investigated the molecular mechanism by which X protein activates NF-kappa B. We demonstrate that in hepatocytes, X protein induces a maximal activation of NF-kappa B corresponding to the sequestered pool of factor, which is also activated by phorbol esters. To determine whether X protein requires activation of PKC to stimulate transcription by NF-kappa B, we attempted to prevent transactivation by X protein in the presence of the PKC inhibitors calphostin C and H7. We show that PKC inhibitors do not block X protein activation of NF-kappa B, whereas they largely impair activation by phorbol esters. In addition, activation of PKC is correlated with its translocation from the cytoplasm to the plasma membrane. The subcellular distribution of PKC was investigated by introducing X protein from a replication-defective adenovirus vector, followed by immunochemical detection of PKC in cell fractions. These data also indicate that X protein stimulates transcription by NF-kappa B without the activation and translocation of PKC.
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PMID:Hepatitis B virus X protein activates transcription factor NF-kappa B without a requirement for protein kinase C. 130 24

A eukaryotic vector-host cell system is described where the additive transactivating effects of HIV-1 tat and adenovirus E1A on HIV-1 long terminal repeat (LTR) are exploited to increase expression of exogenous cDNAs. Human 143B and 293 cells, the latter constitutively producing E1A, were used as host cell lines. The bacterial gene chloramphenicol acetyltransferase (CAT) and the hepatitis B surface antigen (HBs-Ag) gene were employed as reporter genes inserted in pRPneoU3R, an episomal vector containing BK virus replication origin and early region, where cDNAs are expressed under control of HIV-1 LTR. The 293 cells were transformed by tat expression vectors to constitutively express tat. Stable cell clones of 293tat cells, constitutively expressing CAT after transformation with pRPneoU3R-CAT, show a CAT activity 600-fold higher than normal 293 transformed cells. CAT expression obtained in normal 293 cells can be transiently increased 10-fold by transfection by vectors expressing tat. The 293tat cells transformed by pRPneoU3R-HBs, an episomal vector expressing HBs-Ag from HIV LTR, yielded stable cell clones secreting HBs-Ag in the culture medium at a concentration up to 744 ng/ml or 44 ng/10(6) cells/24 h, 48-fold more than normal 293 cells. The use of this system for constitutive or inducible expression of sequences under control of HIV-1 LTR is discussed in view of possible applications for diagnostic, vaccinal and therapeutic purposes.
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PMID:High expression of exogenous cDNAs directed by HIV-1 long terminal repeat in human cells constitutively producing HIV-1 tat and adenovirus E1A/E1B. 182 15

The smallest open reading frame of hepatitis B virus (HBV) has been designated the X gene and its biological function during HBV infection and replication is not known. Experiments described here demonstrate that expression of the HBV X gene in HepG2 cells containing a plasmid with the chloramphenicol acetyltransferase (CAT) gene under control of the human immunodeficiency virus (HIV-1) long terminal repeat (LTR) sequence leads to a marked increase in CAT gene transcription as well as expression of the gene product (CAT). The HIV-1 tatIII gene and the HBV X gene together increased HIV-1 LTR-regulated CAT expression above that observed with either gene alone, suggesting a synergistic effect of the X gene and tat. HBV X gene also stimulated expression of the CAT gene under control of the simian virus 40 enhancer and early promoter but not the visna virus LTR or the human T-cell lymphotropic virus type I (HTLV-I) LTR, indicating that the HBV X gene can transactivate some but not other heterologous viral sequences. Transactivation of the HIV-1 LTR by the HBV X gene varied in different cell lines, suggesting that it may be mediated by a cellular factor(s).
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PMID:Hepatitis B virus X gene can transactivate heterologous viral sequences. 253 28

Hepatitis B virus (HBV) X-gene product activates transcription of the chloramphenicol acetyltransferase (CAT) gene under control of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). To identify a cis-acting regulatory sequence within the HIV-1 LTR which is responsive to the HBV X-gene trans-activating function, we examined the effects of HBV X-gene expression in cells with a series of LTR/CAT deletion mutants. A region of the HIV-1 LTR containing the previously identified kappa B-like enhancer element was found to be responsive to HBV X-gene activation, and this effect was independent of, and additive with, the effect of the HIV-1 tat-III protein on CAT expression. Since kappa B-like enhancer sequences are known to regulate transcription of a variety of viruses and cellular genes, our results suggest that the X gene could activate such a gene during HBV infection and replication.
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PMID:Identification of a region within the human immunodeficiency virus type 1 long terminal repeat that is essential for transactivation by the hepatitis B virus gene X. 272 17

To investigate the possibility of using hepatitis B virus (HBV) as a vector, the tat gene from human immunodeficiency virus type 1 (HIV-1) was inserted into the full-length HBV genome in-frame with the polymerase (pol) open reading frame in the tether region and downstream of the preS1 promoter. We demonstrated that the tat gene was expressed with full activity in transactivating the HIV-1 long terminal repeat (LTR). The expression of the tat gene in the context of the HBV genome in chicken hepatoma and human cervical carcinoma cells, however, was not as efficient as that in human hepatoblastoma cells, which reflects the cellular and species specificity of promoters of hepadnaviruses. Detection of RNA expressed from this HBVtat recombinant revealed transcription of the tat gene by two promoters: the core/pol promoter and the preS1 promoter. A Pol-Tat fusion protein expressed by the core/pol promoter did not seem to contribute to the tat transactivation activity of the HBVtat recombinant since a frameshift mutation in the pol gene did not affect the recombinant tat function. The functional tat protein, therefore, was most likely expressed as a Tat-Pol fusion product. Endogenous polymerase assays showed that the pol protein expressed from the HBVtat recombinant was still active although at a reduced level. Hepatitis B surface antigens and e antigen produced from this recombinant were detected at similar levels as those produced from the wild type. Notably, the capability of forming complete HBV particles was still retained. These studies indicate the potential of constructing HBV as a replicative vector. We also showed that manipulation of a nonreplicative HBV vector was possible. Expression of the HBV polymerase could be completely eliminated and replication of the nonreplicative HBV recombinant could be supported by Pol transcomplementation.
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PMID:Development of replicative and nonreplicative hepatitis B virus vectors. 947 57

Vaccines for the prophylactic and/or therapeutic immunization against hepatotropic pathogens (e.g., hepatitis B and hepatitis C virus) should establish long-lasting, specific antiviral effector/memory CD8+ T cell immunity in the liver. We describe a novel peptide-based vaccine in which antigenic major histocompatibility complex Class I-binding peptides are fused to a cationic (e.g., human immunodeficiency virus tat-derived) domain and complexed to immune-stimulating oligonucleotides. This vaccine formulation efficiently primes liver-homing, Class I-restricted CD8+ effector/memory T cell responses. In different antigen systems, this formulation was more potent in priming liver-homing CD8+ T cell responses than DNA-based vaccines delivering the same epitopes. CD8+ T cell priming was independent of CD4+ T cell "help" but submitted to regulatory control by CD25+ CD4+ T cells. The vaccine efficiently primed memory/effector CD8+ T cells detectable in the liver for more than 3 months after a single injection. With increasing time after priming, the phenotype of these specific memory CD8+ T cells shifted from an effector memory to a central memory type. The vaccine could override T cell tolerance in mice expressing the relevant antigen from a transgene in the liver. The CD8+ T cell immunity in the liver primed by this peptide formulation could be boosted by challenge injections. In conclusion, we describe a simple and potent vaccine formulation that has the potential to generate or reconstitute specific CD8+ T cell immunity to hepatotropic pathogens in the liver.
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PMID:Novel peptide-based vaccines efficiently prime murine "help"-independent CD8+ T cell responses in the liver. 1536 34