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:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An RNA-dependent RNA polymerase activity has been demonstrated for spring viremia of carp virus (SVCV). The optimal temperature for in vitro synthesis of RNA was 20 to 25 degrees C. The SVCV enzyme activity was stimulated when the methyl donor S-adenosyl-L-methionine was included in the reaction mixture. S-adenosyl-L-methionine was not particularly effective in stimulating the virion RNA polymerase activity of vesicular stomatitis virus or pike fry rhabdovirus. The 5' nucleotide of the SVCV viral RNA is pppAp.
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PMID:Spring viremia of carp virus RNA and virion-associated transcriptase activity. 56 17

Of 10,633 blood donations tested in three regional blood transfusion centres with two commercial first generation screening assays for antibodies to the hepatitis C virus (HCV), 65 (0.61%) were found to be repeatedly reactive in one or both assays. Five of the 65 were confirmed positive by recombinant immunoblot assay (Ortho RIBA-2) and a further 4 were judged indeterminate. All 5 RIBA-2 positive donations and 1 of the 4 RIBA-2 indeterminates were shown to be viraemic by HCV-RNA polymerase chain reaction (PCR) assays performed at three independent reference laboratories. The remaining 56 screen test reactive donations proved negative by RIBA-2 and, with 1 exception, negative by PCR. We conclude that while first generation anti-HCV screening assays generate a high proportion of false reactions when screening low prevalence populations, results of the RIBA-2 confirmatory test correlate well with PCR findings and thus indirectly with both hepatitis C viraemia and infectivity.
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PMID:Hepatitis C viraemia in United Kingdom blood donors. A multicentre study. 132 12

The retroviruses human T-cell lymphotrophic virus-I (HTLV-I) and HTLV-III/LAV (lymphadenopathy-associated virus) are clearly linked to human diseases. Patients with HTLV-I-positive neoplasms may respond transiently to traditional chemotherapy, but are not cured. For patients with acquired immune deficiency syndrome (AIDS) there is no curative therapy. In retroviruses of different species, viral propagation crucially depends on reverse transcriptase, an enzyme not present in normal mammalian cells and different from mammalian DNA polymerases, making it a target for specific inhibition. Reverse transcriptase has been well conserved through evolution: an LAV isolate contained a 250-amino-acid-long domain, presumably the reverse transcriptase core sequence, which has 21% homology to Moloney murine leukaemia virus (MoMLV). Because HTLV-III infects only humans and chimpanzees, we substituted murine retroviruses for in vivo evaluation of candidate anti-AIDS drugs after ascertaining similar inhibition in vitro of HTLV-III and MLVs, which were chosen for their short incubation time. The triphosphate of 3'-azido-3'-deoxythymidine (AZT) is incorporated into complementary DNA by retroviral reverse transcriptase, causing premature chain termination. Here we show that chronic AZT treatment of mice infected with Rauscher murine leukaemia virus complex (RLV) prevents infection of splenocytes and development of splenomegaly, and suppresses viraemia if started soon after inoculation. Starting AZT late in the course of disease still leads to significant prolongation of life; anaemia, however is a significant side-effect. By analogy, AZT may have a role in preventing retroviral disease in humans if started early after infection, and it may lead to significant survival gains even if started later in the course of disease.
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PMID:Suppression of mouse viraemia and retroviral disease by 3'-azido-3'-deoxythymidine. 346 67

S-Adenosyl-L-methionine (SAM), a methyl donor, and its analogue S-adenyl-L-homocysteine (SAH), an inhibitor of methylation, stimulate the activity of spring viraemia of carp virus (SVCV) virion transcriptase. The stimulation observed for SVCV is analogous to that observed previously (Furuichi, 1974, 1978) for a totally unrelated virus, cytoplasmic polyhedrosis virus (CPV). In the absence of exogenous SAM, RNA with 5'-methylated termini (presumptive GpppAmpAp) was produced, indicating that SVCV has an endogenous methyl donor. Significantly less methylated termini were produced when SVCV nucleocapsids were used to prime in vitro transcription reactions, suggesting that the majority of the endogenous methyl donor is not associated with the nucleocapsid. Partial removal of endogenous methyl donor by preparing nucleocapsids did not have any effect on the degree of stimulation by exogenous SAM or SAH. We conclude from this study that SAH has two effects on SVCV transcription, inhibition of methylation and stimulation of transcription.
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PMID:Stimulation of transcription by S-adenosyl-L-homocysteine and virion-encapsidated methyl donor in spring viraemia of carp virus. 727 15

Fifty-seven sera with indeterminate results by the second generation RIBA (RIBA 2) for confirmation of hepatitis C virus (HCV) enzyme linked immunoassay (ELISA) reactivity were tested by the new third generation RIBA (RIBA 3). Thirty three (57.9%) displayed reactivity for at least one other band and were therefore classified as positive; two became negative and 22 (38%) remained indeterminate. The incidence of HCV viremia, as determined by the RNA polymerase chain reaction (PCR), was 75% for the latter sera. The data show that it is important to subject RIBA 3 indeterminate samples to PCR.
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PMID:Enhanced detection of antibodies to hepatitis C virus by use of a third-generation recombinant immunoblot assay. 752 81

We report a prospective clinical and virological study of 18 patients undergoing orthotopic liver transplantation, selected because of hepatitis C virus (HCV) RNA positivity before transplantation. Nine of the 18 patients (50%) developed chronic active hepatitis (CAH) in liver allografts during the first year posttransplantation; hepatitis was first observed between 6 and 25 weeks posttransplantation. HCV viremia was measured for all patients before transplantation and on posttransplantation days 3, 7, and 14, and months 1, 6, 12, and 24 to 41, by quantitative competitive RNA polymerase chain reaction (QC-PCR). HCV RNA levels on posttransplantation days 3, 7, and 14 were significantly higher among patients who subsequently developed CAH versus those who did not (P < .02 by t-test and Mann-Whitney test on all three dates). However, HCV RNA levels in sera obtained at 1, 6, and 12 months posttransplantation did not correlate with CAH at 1 year or with HCV genotype determined in posttransplantation sera. At least two serial liver biopsy specimens from each patient were stained for HCV nonstructural 4 (NS4) antigen by immunohistochemistry. The intensity of cytoplasmic staining of NS4 antigen was significantly higher for specimens with CAH versus those without CAH (P = .028 by chi 2). Three patients developed bridging fibrosis in liver allografts during the first year after transplantation; all three patients had intense (3+) immunostaining for NS4 antigen, and the infecting genotypes were 1a, 1b, and 1a plus 1b, respectively. In summary, the 18 patients all developed high-titer viremia by 1 month after liver transplantation, whereas CAH developed in 50% of allografts during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistent hepatitis C virus infection after liver transplantation: clinical and virological features. 754 38

Six recombinant Japanese encephalitis virus (JEV) isolates were recovered from infectious RNAs transcribed by T7 RNA polymerase from molecularly cloned cDNA templates. Three of the recombinant viruses had characteristics similar to the wild-type parent virus, JaOArS982. The other 3 recombinant viruses exhibited an attenuated phenotype in mice. An avirulent recombinant virus, IC47, was characterized and compared with the wild-type parent virus and a virulent recombinant virus, IC37. IC47 produced smaller plaques than parent or IC37 viruses and exhibited no viremia or neuroinvasion in young adult mice inoculated subcutaneously and no mortality when inoculated intracerebrally. IC47 was also immunogenic and protective in the murine model. The probable basis for attenuation, revealed by nucleotide sequence analysis, was a single amino acid substitution at position 138 (Glu to Lys) in the E protein.
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PMID:Characterization of a highly attenuated Japanese encephalitis virus generated from molecularly cloned cDNA. 775 89

HIV PROTEINASE INHIBITORS: The HIV proteinase enzyme has been identified as a potential target for antiretroviral therapy, as inhibition of this enzyme leads to the generation of immature, non-infectious virions. There are several proteinase inhibitors in development; the first to enter clinical trials was saquinavir. DEVELOPMENT OF SAQUINAVIR: Saquinavir, a transition-stage analogue of an HIV proteinase cleavage site, was developed using computer-led rational design techniques. It is a highly specific inhibitor of HIV-1 and -2 proteinases, with antiviral activity at concentrations 1000-fold less than those causing cytotoxicity. EUROPEAN CLINICAL EXPERIENCE WITH SAQUINAVIR: Three European clinical studies involving 202 patients have been conducted with saquinavir at doses of 25, 75, 200 and 600 mg three times a day. Two studies were dose-ranging monotherapy trials, one in asymptomatic or mildly symptomatic patients not previously treated with zidovudine, the other in patients with advanced HIV infection who had been treated with zidovudine. The third study was a combination therapy trial with zidovudine in previously untreated patients with advanced infection. Saquinavir was well tolerated either alone or in combination with zidovudine. In the monotherapy studies, CD4 cell counts and estimates of viral load showed the best results with the 600-mg dose. The combination of saquinavir and zidovudine resulted in higher and more sustained increases in CD4 cell counts than with either drug alone. The CD4 cell counts favoured saquinavir at 200 and 600 mg in combination with zidovudine, although plasma viraemia and the RNA polymerase chain reaction indicated that the 600-mg dose (in combination) produced better responses.
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PMID:HIV therapy advances. Update on a proteinase inhibitor. 784 Sep 13

Sera from 39 out of 40 patients with chronic hepatitis C virus (HCV) infection who had been treated for 60 weeks with interferon alfa-2b proved initially HCV RNA positive by reversed transcriptase polymerase chain reaction (PCR). These patients were analysed for genotype and quantitatively for HCV RNA levels prior to treatment by using a competitive PCR method with colorimetric detection of the amplified products. HCV RNA levels were correlated to outcome of treatment, mode of acquisition, histology and HCV genotype. The median pretreatment HCV RNA level in sustained responders (n = 15) with eradication of the viremia and normalization of serum ALT levels lasting 24 weeks post treatment was significantly lower than that in the combined group of non-sustained responders (n = 9) and non-responders (n = 15), 2.52 x 10(5) vs 8.90 x 10(5) genome equivalents per ml serum, p < 0.0125, respectively. 10 out of 17 patients with HCV RNA levels lower than the median level (5.64 x 10(5) genome equivalents per ml serum) had a sustained response to interferon treatment versus only 5/22 with levels equal to or higher than the median level, p = 0.04. No significant pretreatment differences in median HCV RNA levels according to mode of acquisition, genotype, or liver histology prior to treatment were seen. It is concluded that a low pretreatment HCV RNA level seems to be indicative of a sustained response to interferon alfa-2b treatment, whereas a high level seems to be indicative of a non-sustained or non-response. In the individual patient, however, the levels varied widely irrespective of response category.
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PMID:Serum hepatitis C virus RNA levels in chronic hepatitis C--importance for outcome of interferon alfa-2b treatment. 793 25

A quantitative competitive RNA polymerase chain reaction (QC-PCR) assay was developed for measuring absolute levels of hepatitis C virus (HCV) RNA in the sera of 121 viremic persons, including 64 asymptomatic blood donors, 39 symptomatic patients referred for treatment of chronic hepatitis C, and 18 patients with end-stage liver disease referred for liver transplantation. Mean HCV RNA levels (log molecules per milliliter) were lowest among blood donors with normal alanine aminotransferase (ALT) values (5.8 +/- 1.5), higher among blood donors with elevated ALT (6.9 +/- 0.8) and clinic patients with chronic active hepatitis (6.9 +/- 0.7), and highest among patients with cirrhosis (7.1 +/- 0.8) or end-stage liver disease (7.6 +/- 1.0). High-titer viremia ( > or = 7.5 logs/mL) was more frequent among patients with end-stage liver disease (14/18; 78%) than either blood donors (10/64; P < .001) or patients with chronic active hepatitis (7/26; P < .001). Thus, 121 (94.5%) of 128 anti-HCV-positive persons were viremic. QC-PCR may be valuable for monitoring HCV infection status and selecting individuals for therapy.
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PMID:Assessment of hepatitis C virus RNA levels by quantitative competitive RNA polymerase chain reaction: high-titer viremia correlates with advanced stage of disease. 819 99


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