Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We characterized 11 DNA polymerase mutants of human hepatitis B virus (HBV) which contain single missense or nonsense mutations in the various domains within this gene. Except for mutant 738, a tight association between DNA replication and RNA packaging of these missense pol mutants was observed. Further analysis of HBV core particle-associated RNA indicated that only the 3.5-kb core-specific RNA, but not the precore-specific RNA, is selectively packaged in this tissue culture system. Previously, we have demonstrated that only the 3.5-kb core-specific RNA can serve as an efficient template for pol translation. Taken together, our results suggest that selectivity of HBV RNA packaging occurs as a result of selective translation of pol-containing mRNAs. Furthermore, our data suggest that the RNA encapsidation domain of pol overlaps with all of the domains of pol involved in the synthesis of terminal protein, as well as DNA replication. Finally, on the basis of gradient centrifugation analysis, a pol defect appeared to have no negative effect on the assembly or stability of core particles. A new method to assay RNA encapsidation, as well as potential RNase H activity, is reported.
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PMID:Pregenomic RNA encapsidation analysis of eleven missense and nonsense polymerase mutants of human hepatitis B virus. 171 Feb 85

The presence of pre-S1 proteins in peripheral blood mononuclear cell (PBMC) samples from 115 patients with different forms of hepatitis B virus (HBV) infection was investigated by Western blot. Among 67 chronic HBsAg carriers, HBV antigens were detected in the PBMC in 80% for HBsAg, 27% for HBc/e Ag and 34% for pre-S1 proteins. The detection of pre-S1 proteins in PBMC was significantly associated with the presence of serum markers of HBV replication (HBV DNA and/or DNA polymerase). In the group of 48 consecutive patients negative for serum HBsAg, but positive for anti-HBc with or without anti-HBs, HBsAg and pre-S1 proteins could be detected in PBMC. This finding was more frequent among anti-HIV-positive patients (77 and 23% of the cases, respectively) than in the negative ones (23 and 4% of the cases, respectively). The detection of HBV DNA and polyadenylated RNA in some of the PBMC samples positive for HBV proteins suggests that these proteins may be expressed in PBMC, especially during intense HBV replication. In patients negative for serum HBsAg, PBMC may constitute a reservoir of HBV.
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PMID:Detection of pre-S1 proteins in peripheral blood mononuclear cells from patients with HBV infection. 171 Oct 65

Among 262 inpatients with hematologic diseases who were referred for chemotherapy or immunosuppressive therapy between January, 1985, and December, 1989, nine (3.4%) patients, including two with Hodgkin's disease (HD), three with acute myeloblastic leukemia, one with chronic myelogenous leukemia, two with multiple myeloma and one with aplastic anemia, were found to be hepatitis B virus (HBV) carriers before their chemotherapy began. All six HBV carriers who received chemotherapy containing glucocorticoid showed mild-to-moderate elevations in serum transaminase levels after the chemotherapy. Five showed a rise in titer of the hepatitis B surface antigen, HBsAg. In contrast, three HBV carriers not receiving glucocorticoid showed no change in serum transaminase after chemotherapy. One HBV carrier with HD suffered from severe icteric hepatitis after the withdrawal of multiagent chemotherapy containing glucocorticoid. The HBV-DNA polymerase rose markedly and was accompanied by a marked rise in titer of HBsAg. The results warn us to keep in mind the possibility of glucocorticoid inducing an activation of HBV infection, which may result in severe hepatitis in some HBV carriers. Although further investigation is required, it is recommended that HBsAg-positive patients with hematologic malignancies should, if possible, be treated without glucocorticoid.
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PMID:Activation of hepatitis B virus infection by chemotherapy containing glucocorticoid in hepatitis B virus carriers with hematologic malignancies. 175 16

Seventeen patients with chronic hepatitis B were treated with a 4-week administration of glycyrrhizin followed by a 4-week treatment with human lymphoblastoid interferon, then followed for 6 months after the end of treatment. All were positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B virus-associated DNA polymerase (DNA-p) for at least 6 months before entry. All patients were Japanese and none of them were homosexuals. Eleven patients lost DNA-p activity and 10 of them lost HBeAg. Three of these 10 patients had antibody to HBeAg. In 10 patients who became HBeAg-negative, alanine aminotransferase levels after glycyrrhizin administration were higher and initial DNA-p activities relatively lower than the levels found in seven patients who remained HBeAg-positive. The immunomodulator provided by a short course of glycyrrhizin before administration of human lymphoblastoid interferon may be an effective treatment for patients with chronic hepatitis B.
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PMID:Glycyrrhizin withdrawal followed by human lymphoblastoid interferon in the treatment of chronic hepatitis B. 176 47

The acyclic nucleoside phosphonate analogues (HPMPA, HPMPC, PMEA, FPMPA) show great promise for the treatment of infections with such important human pathogens as adeno, pox (vaccinia) and hepadna (hepatitis B) viruses (HPMPA), herpes (herpes simplex, varicella-zoster, cytomegalo, Epstein-Barr) viruses (HPMPC), and retro (human immunodeficiency) viruses (PMEA, FPMPA). All these compounds seem to be targeted at the viral DNA polymerase, with which they interact, as either competitive inhibitors or alternative substrates (or chain terminators), following their intracellular phosphorylation to the diphosphoryl derivatives. Of particular interest is the prolonged anti-viral action, lasting for several days or even weeks, that has been noted both in vitro and in vivo after a single administration of the acyclic nucleoside phosphonates.
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PMID:Chemotherapy of the acquired immune deficiency syndrome (AIDS): acyclic nucleoside phosphonate analogues. 182 10

Of a series of 14 nucleoside 5'-triphosphates, those of 2',3'-dideoxy-3'-fluoro-5-methylcytidine, 3'-azido-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3'-fluoroguanosine, 2',3'-didehydro-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3'-fluoro-5-ethylcytidine, and 2',3'-dideoxy-3'-fluoroadenosine emerged as the most potent inhibitors of hepatitis B virus DNA polymerase (50% inhibitory dose, 0.03 to 0.35 microM). In contrast, cellular DNA polymerases proved to be resistant to (alpha) or partially affected by (beta) these analogs. These compounds are among the most effective and selective inhibitors of endogenous hepatitis B virus DNA polymerase recognized to date.
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PMID:Comparative inhibition of hepatitis B virus DNA polymerase and cellular DNA polymerases by triphosphates of sugar-modified 5-methyldeoxycytidines and of other nucleoside analogs. 192 76

Hepatitis B virus (HBV) variants with a nonsense mutation in the distal pre-C region have been detected in patients positive for anti-HBe, and the complete nucleotide sequence of one cloned pre-C variant has been determined. Transfection of this HBV variant clone into the human hepatoma cell line HepG2 resulted in the appearance of major HBV transcripts, replicative forms of viral DNA evidenced by both molecular hybridization and endogenous DNA polymerase assay, as well as the expression and secretion of HBsAg and HBcAg particles. Western blotting revealed only the 21-kDa HBcAg but not the 17-kDa HBeAg. These results demonstrate the replication capacity of the HBV variant with a nonfunctional pre-C region despite its inability to express HBeAg.
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PMID:In vitro replication competence of a cloned hepatitis B virus variant with a nonsense mutation in the distal pre-C region. 201 46

An efficient method for cloning subgenomic fragments of the hepatitis B virus (HBV) was developed, utilizing its abundant single-stranded replicative intermediates. The total genomic DNA obtained from the liver tissue of patients with chronic HBV infection was treated by using the Klenow fragment of E. coli DNA polymerase I without adding any exogenous primers. Single-stranded replicative intermediates were efficiently converted to double-stranded linear DNA, one end of which terminated at (or near to) the direct repeat 1 (DR1) sequence of the HBV genome. By screening less than 1,000 recombinants from a DNA library after this treatment, we obtained a subgenomic HBV fragment of 2.0 kilobases. We then analysed HBV RNA in human liver tissue by S1 mapping. It was possible to map HBV RNA only when a DNA probe from the same tissue was used.
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PMID:Efficient cloning of hepatitis B virus DNA from single-stranded replicative intermediates and its application to S1 mapping of viral RNA in human liver tissue. 201

Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity.
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PMID:No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection. 203 94

The genome of the duck hepatitis B virus (DHBV) contains an enhancer element. This sequence, of 192 bp, is located in the 3'-terminal coding region of the DNA polymerase gene (nucleotides 2159 to 2351), upstream from the pregenomic RNA start site. This enhancer potentiates a marked increased activity from the heterologous thymidine kinase promoter in an orientation-independent manner and at a proximal, as well as a distal, location. The DHBV enhancer activates transcription in a relatively cell-type-independent manner. Sequence homologies with the nuclear factor EF-C binding site are located in the DHBV enhancer. By using the HepG2 nuclear extracts and the DHBV enhancer as probes, a complex was observed in mobility shift assays.
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PMID:Identification of a strong enhancer element upstream from the pregenomic RNA start site of the duck hepatitis B virus genome. 204 Oct 96


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