Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The duck hepatitis B virus (DHBV)-associated activities of reverse transcriptase and DNA polymerase and their inhibition in vitro were studied. Replicative complexes (RCs) were isolated from DHBV-infected liver by gel chromatography followed by sucrose gradient centrifugation. The RCs were detected by dot blot hybridization, using radiolabeled cloned DHBV DNA as a probe, and by the incorporation of 32P-TTP in the presence of dATP, dCTP, dGTP, and Mg2+ (endogenous DNA polymerase activity). The endogenous DNA polymerase activity associated with RCs was further studied using exogenous templates: reverse transcriptase and DNA polymerase activities were demonstrated using as substrates 32P-TTP and poly(rA) p(dT)12 or poly(dA) p(dT)12-18, respectively. Both activities were biochemically characterized. Their inhibition by various antiviral agents was studied in vitro: actinomycin D, ara-ATP, aphidicolin, suramin, chloroquin, and phosphonoformate. Among these, suramin, chloroquin, phosphonoformate, and ara-ATP were shown to be potent inhibitors of viral reverse transcriptase and DNA polymerase. Studies are now in progress to establish their antiviral activity in vivo.
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PMID:Duck hepatitis B virus: DNA polymerase and reverse transcriptase activities of replicative complexes isolated from liver and their inhibition in vitro. 245 18

Suramin blocked in vitro infection by duck hepatitis B virus, a hepadnavirus, and Rous sarcoma virus, a retrovirus. Although suramin was able to inhibit the virus-encoded reverse transcriptase activities of these two viruses, this inhibition did not appear to account for the anti-viral effect of the drug. In particular, suramin was unable to block synthesis within cells of full-length viral DNAs when added subsequent to infection. The results are consistent with the hypothesis that suramin acted by blocking virus uptake or uncoating. As further support of this hypothesis, we found that suramin also blocked infection by hepatitis delta virus, an RNA virus that is not known to employ reverse transcriptase during the initiation of infection.
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PMID:Suramin inhibits in vitro infection by duck hepatitis B virus, Rous sarcoma virus, and hepatitis delta virus. 246 6

The expression strategy of the duck hepatitis B virus (DHBV) P gene, which is assumed to encode the viral reverse transcriptase, was investigated by mutational analysis. This study showed that P gene expression starts in the region where the P gene overlaps the viral core gene. However, in contrast to retroviral reverse transcriptases, which are expressed via gag-pol fusion protein intermediates, the DHBV P gene product was found to be synthesized starting at a P gene ATG codon. The resulting protein can complement polymerase-negative mutants in trans and can reverse transcribe viral pregenomic RNA that does not encode an active polymerase. These findings raise the question of how reverse transcription of cellular RNAs can be avoided in infected cells.
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PMID:Synthesis and encapsidation of duck hepatitis B virus reverse transcriptase do not require formation of core-polymerase fusion proteins. 246 93

We have used activity gel analysis and immunoblotting to provide evidence linking the hepatitis B virus (HBV) reverse transcriptase with its longest unassigned open reading frame (polymerase [Pol]-ORF). Activity gel analysis demonstrated that infectious HBV particles secreted by the Hep 2.2.15 cell line contain major (approximately 70 kilodaltons [kDa]) and minor (approximately 90 kDa) reverse transcriptase activities. By Western immunoblotting, we detected in both HBV particles and Hep 2.2.15 cell extract a approximately 70-kDa Pol-specific peptide. This approximately 70-kDa peptide reacted with antisera directed against the carboxy terminus of the pol gene product. No such immunoreactivity was observed with antisera against the amino terminus of the Pol peptide. The reverse transcriptase protein which was eluted from the major approximately 70-kDa region detected on an activity gel reacted with Pol-specific antisera. Furthermore, reverse transcriptase activity was immunoprecipitated from dissociated HBV particles by using Pol-specific antisera. On the basis of our results, we suggest that HBV encodes its reverse transcriptase from the Pol-ORF.
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PMID:The hepatitis B virus-associated reverse transcriptase is encoded by the viral pol gene. 246 75

Retroviruses and many other types of genetic elements replicate by reverse transcription of RNA. Although structurally and biologically very diverse, such elements carry conserved polymerase genes (pol) that encode proteins required for reverse transcription. In most cases, the pol gene is preceded by an overlapping gene encoding one or more nucleocapsid proteins, in a different reading frame. Because both coding regions are represented in a single mRNA, the question arises of how the reverse transcriptase in the alternative reading frame is expressed. In retroviruses and retrotransposons it is expressed as a nucleocapsid-polymerase fusion protein by ribosomal frameshifting during translation of the overlapping region. We have examined the mechanism of polymerase biosynthesis in another family of animal viruses that use reverse transcription, the hepatitis B viruses. Genetic and biochemical studies reveal that these viruses do not use ribosomal frameshifting to generate this enzyme, but instead direct translation initiation at an internal initiation (AUG) codon in the polymerase gene.
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PMID:Biosynthesis of the reverse transcriptase of hepatitis B viruses involves de novo translational initiation not ribosomal frameshifting. 246 89

Hepatitis B virus (HBV), like retroviruses, replicates through reverse transcription. However, the identity and mechanism for the synthesis of HBV reverse transcriptase remain unknown. The open reading frame (ORF) for HBV putative reverse transcriptase (pol), as a consequence of overlapping with the whole ORF of envelope proteins (hepatitis B surface antigens), includes a hypervariable region at the N terminus. Thus, compared with retroviruses, it is unlikely that HBV reverse transcriptase is translated from complete pol ORF in the full-length pregenomic RNA. We have now detected in infected human livers a novel doubly spliced RNA in which one splicing event removed the hypervariable region of the pol gene but retained the conserved region homologous to retroviral reverse transcriptase. The other splicing event deleted the central region of hepatitis B core antigen and thus brought the protease domain which is important for maturation of reverse transcriptase close to that of pol. For this sequence organization, the spliced RNA as the possible template for the synthesis of HBV reverse transcriptase is discussed.
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PMID:Identification of a doubly spliced viral transcript joining the separated domains for putative protease and reverse transcriptase of hepatitis B virus. 247 67

The effect of 2',3'-dideoxycytidine, a potent antiviral agent, which, following anabolic phosphorylation, inhibits the reverse transcriptase of the human immunodeficiency virus in vitro, was assessed in 16 Pekin ducks chronically infected with the duck hepatitis B virus. Nine ducks were given 11 mg/m2 of dideoxycytidine intravenously every 6 h, and 7 ducks received no treatment. Serum duck hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity decreased in every duck treated with dideoxycytidine. The mean inhibition of deoxyribonucleic acid polymerase and duck hepatitis B virus deoxyribonucleic acid on the third day of treatment measured 64% (p less than 0.01) and 73% (p less than 0.01), respectively. The inhibition of deoxyribonucleic acid polymerase persisted after treatment was stopped, and 4 ducks continued to show greater than 50% inhibition 12 days after stopping treatment. Duck hepatitis B virus deoxyribonucleic acid, which was measured in total cellular deoxyribonucleic acid extracted from liver biopsy specimens obtained before and on the last day of treatment with dideoxycytidine, showed an average inhibition of 96% in 3 ducks treated with dideoxycytidine, but showed no decrease in the remaining 5 ducks. Thus, dideoxycytidine has potent antiviral activity against duck hepatitis B virus and warrants further evaluation as an antiviral agent in the treatment of chronic hepatitis B virus infection in humans.
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PMID:Inhibition of duck hepatitis B virus replication by 2',3'-dideoxycytidine. A potent inhibitor of reverse transcriptase. 247 99

The DNA polymerase of hepadnaviruses has two different functions during virus replication. It acts both as an RNA-dependent DNA polymerase (reverse transcriptase) and as a DNA-dependent DNA polymerase. Duck hepatitis B virus (DHBV) preparations were used to investigate the inhibitory effects of selected compounds on these two enzyme activities. The reverse transcriptase activity was represented by an actinomycin D-resistant, phosphonoformate-sensitive DNA polymerase activity isolated from DHBV-infected duck livers. DHBV from serum was used as the source of the DNA-dependent DNA polymerase activity. Pyrophosphate and nucleoside triphosphate analogs were assayed for their inhibitory effects on the two enzyme preparations. A marked inhibition was obtained with 3'-fluoro-2',3'-dideoxythymidine 5'-triphosphate, acyclovir triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, 2',3'-dideoxyguanosine 5'-triphosphate and 2',3'-dideoxythymidine 5'-triphosphate. The two thymidine analog triphosphates showed a markedly lower inhibitory effect on the reverse transcriptase activity than on the DNA-dependent DNA polymerase activity. This was in analogy with earlier findings with 3'-azido-2',3'-dideoxythymidine 5'-triphosphate. Among the tested pyrophosphate analogs only phosphonoformate was inhibitory.
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PMID:Inhibition of RNA- and DNA-dependent duck hepatitis B virus DNA polymerase activity by nucleoside and pyrophosphate analogs. 248 79

We have previously described model systems for cytokine-induced regulation of chronically HIV-infected promonocyte and T cell clones. Using these systems, we have shown that monokines contained in supernatants from LPS-stimulated human monocyte/macrophages (MO) up-regulate HIV expression, reflected by an increase in reverse transcriptase activity, viral RNA levels, and expressed viral proteins. Current studies were designed to determine whether viral Ag can interact with MO and secondarily affect HIV1 expression by stimulating monokine production. We found that certain herpes-group viruses, including CMV and EBV, augment HIV1 expression by inducing monokine production, whereas others, such as HSV1, HSV2, varicella-zoster virus, and human herpes virus 6 were unable to function in this capacity. The HSV1 and HSV2 Ag which failed to stimulate monokine production did not interfere with MO stimulation by CMV Ag, suggesting that failure to induce HIV expression was not attributable to MO suppression. When nonherpes group viruses were tested, we found that human adenovirus, hepatitis B virus, and vaccinia virus all failed to stimulate the production of monokines capable of activating HIV in the chronically infected cell lines. In contrast, HIV1 can augment its own expression by inducing the secretion of monokines which up-regulate HIV expression in the infected cells. The viral Ag-induced MO supernatants capable of up-regulating HIV expression did so in a dose-dependent manner, whereas viral Ag alone produced no significant change. Monokine production mediated by viral Ag was not attributable to contaminating endotoxin. These studies provide a model to determine whether other opportunistic infections may induce the expression of HIV by indirect mechanisms, such as the stimulation of cytokine production.
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PMID:Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. 254 45

3'-Azido-3'-deoxythymidine (AZT) inhibits the replication of the human immunodeficiency virus (HIV) by blocking the formation of the phosphodiester bond and has been used clinically for the treatment of HIV infection. To assess the effect of AZT on the replication of hepadnaviruses, which replicate through reverse transcription, both the liver tissue and primary cultured hepatocytes from ducklings previously infected with duck hepatitis B virus (DHBV) were examined for DHBV DNA before and after the treatment with AZT. We did not observe suppression of DHBV replication at any doses in our system as measured by viral DNA synthesis in infected duck hepatocytes. The data strongly suggest that AZT has no inhibitory effect on DHBV reverse transcriptase.
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PMID:Effect of 3'-azido-3'-deoxythymidine on replication of duck hepatitis B virus in vivo and in vitro. 255 51


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