Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of a single-stranded polynucleotide copolymer containing 9% cytidine residues and 91% 4-thiouridine residues [poly(C,S4U10)], a known potent inhibitor of the virion transcriptase of influenza viruses, suppressed the amount of virus recoverable from the nasal washes of influenza virus-infected hamsters and ferrets. The incidence of sneezing and nasal discharge in infected ferrets was also reduced. In hamsters, poly(C,S4U10) was more effective than amantadine-HCl or Virazole. Polyinosinic acid in combination with poly-5-hydroxy cytidylic acid also had anti-influenza effects. Poly(C,S4U10) annealed to polyadenylic acid was not effective, nor was the double-stranded polymer (polyinosinic acid) . (polycytidylic acid) even when complexed with carboxymethylcellulose and polylysine. No toxic effects of poly(C,S4U10) were apparent in the treated hamsters and ferrets, and high doses (greater than or equal to 2.86 g/kg) administered intraperitoneally to mice produced no adverse effects.
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PMID:Antiviral effects of single-stranded polynucleotide inhibitors of the influenza virion-associated transcriptase against influenza virus infection of hamsters and ferrets. 628 Jun 8

Virus-specific protein and RNA syntheses have been analyzed in chicken embryo fibroblast cells infected with two group IV temperature-sensitive (ts) mutants of influenza A (fowl plague) virus in which the ts lesion maps in RNA segment 8 (J. W. Almond, D. McGeoch, and R. D. Barry, Virology 92:416-427, 1979), known to code to code for two nonstructural proteins, NS1 and NS2. Both mutants induced the synthesis of similar amounts of all the early virus-specific proteins (P1, P2, P3, NP, and NS1) at temperatures that were either permissive (34 degrees C) or nonpermissive (40.5 degrees C) for replication. However, the synthesis of M protein, which normally accumulates late in infection, was greatly reduced in ts mutant-infected cells at 40.5 degrees C compared to 34 degrees C. The NS2 protein was not detected at either temperature in cells infected with one mutant (mN3), and was detected only at the permissive temperature in cells infected with mutant ts47. There was no overall reduction in polyadenylated (A+) complementary RNA, which functions as mRNA, in cells infected with these mutants at 40.5 degrees C compared to 34 degrees C, nor was there any evidence of selective accumulation of this type of RNA within the nucleus at the nonpermissive temperature. No significant differences in ts mutant virion RNA transcriptase activity were detected by assays in vitro at 31 and 40.5 degrees C compared to wild-type virus. Virus-specific non-polyadenylated (A-) complementary RNA, which is believed to act as the template for new virion RNA production, accumulated normally in cells at both 34 and 40.5 degrees C, but at 40.5 degrees C accumulation of new virion RNA was reduced by greater than 90% when compared to accumulation at 34 degrees C.
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PMID:Influenza virus-specific RNA and protein syntheses in cells infected with temperature-sensitive mutants defective in the genome segment encoding nonstructural proteins. 644 1

Analogues of the mRNA 5'-terminal methyl cap structure were found to stimulate the influenza virion RNA-dependent RNA polymerase. The single nucleotide analogue m7GMP was incorporated into RNA during transcription in vitro, and the stimulatory effect was not additive with the primer ApG, suggesting that m7GMP stimulates the virion polymerase by priming virus-specific mRNA synthesis, as has been shown for ApG. By contrast, stimulation by m7G(5')ppp(5')m6AM2-O was additive with that by ApG, and we could not demonstrate incorporation of the similar analogue m7G(5')ppp(5')Am2-O into RNA during transcription. We propose that these dinucleotide cap analogues stimulate the virion polymerase by allosteric modulation, independent of priming. This stimulation can be abolished by mutation, without loss of other activities associated with the cap-dependent endonuclease.
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PMID:Capped mRNAs may stimulate the influenza virion polymerase by allosteric modulation. 653 99

Coumermycin A1, a Novobiocin related antibiotic, has been tested in vivo and in vitro for its activity on Influenza A viruses. In a range of concentrations between 3 and 5 micrograms/ml virus production was drastically reduced. The drug was able to inhibit virus release into culture medium also if added up to the sixth hour following infection and its action was reversible within this time. The synthesis of virus induced polypeptides was generally depressed but production of the HA was more deeply inhibited. Viral transcriptase activity in vitro was also affected by the presence of Coumermycin A1 but at doses which seem to high to consider this event as a phenomenon likely to play a role in vivo. It is suggested that the antiviral activity of the drug is mediated by the inhibition of the host cell metabolism.
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PMID:Effect of coumermycin on influenza A virus replicative cycle. 654 62

The transcriptase activity of original mouse-apathogenic strains of human (A/USSR/05/81) and animal (A/walrus/Massachusetts/1/80) influenza viruses and their pathogenic variants was studied. Also RNA-polymerase was studied in two types of antigenic recombinants produced by hybridization of the parental strains one of which (A/PR8/34) was pathogenic for mice. The nonpathogenic viruses under study were shown to have a low transcriptase activity, while pathogenic variants of these strains had a higher RNA-polymerase activity (1 1/2-3 times higher than in the original virus). All the recombinants tested, irrespective of their pathogenicity, had approximately similar transcriptase activity, 1 1/2-2 times higher than the enzymatic activity of the parental nonpathogenic virus.
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PMID:[RNA-polymerase activity of pathogenic and nonpathogenic influenza A virus variants]. 673 Apr 32

The transcriptase activity of influenza A virus ribonucleoproteins was inhibited by 42 to 49% in vitro in the presence of membrane (M) protein. The addition of M protein to the system of ribonucleoprotein preparations isolated from rimantadine-sensitive or rimantadine-resistant influenza virus strains, as well as the addition of M protein isolated from a sensitive strain, in the presence of rimantadine further inhibited the transcriptase activity of such complexes by approximately 40%. In the system containing the same ribonucleoprotein preparations, but with M protein isolated from a rimantadine-resistant influenza virus strain, the transcriptase activity was not sensitive to rimantadine. The data show that M protein can influence the activity of influenza A virus virion transcriptase and that the susceptibility of influenza virus to rimantadine may be due to the peculiarities of M protein.
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PMID:Influence of membrane (M) protein on influenza A virus virion transcriptase activity in vitro and its susceptibility to rimantadine. 689 43

Eleven temperature-sensitive (ts) mutants of influenza A (fowl plague, Rostock) virus were analysed for in vitro RNA transcriptase activity in reactions primed by ApG or globin mRNA at 31 degrees C or at 40.5 degrees C, the restrictive temperature for ts mutant growth. Only those ts mutants studied which were defective in RNA segment 1, coding for the virion P2 protein, were defective in RNA transcriptase activity when compared to wild-type virus. Mutants having a defect in the P2 protein had no significant RNA transcriptase activity in reactions at 40.5 degrees C primed by globin mRNA. However, one mutant showed RNA transcriptase activity similar to wild-type virus at 40.5 degrees C when ApG (0.3 mM) was used as primer. The results suggest that influenza (fowl plague, Rostock) P2 protein is directly involved in the mRNA priming reaction, as well as in the RNA transcription reaction in vitro.
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PMID:Evidence for the involvement of influenza A (fowl plague Rostock) virus protein P2 in ApG and mRNA primed in vitro RNA synthesis. 689 49

Capped ribopolymers lacking a sequence complementary to the common 3' end of the influenza virion RNA segments effectively stimulated transcription of these RNAs by the virion-associated transcriptase. Thus, stimulation of transcription results not from hydrogen bonding between the capped RNA and the 3' end of the virion RNA but presumably from a specific interaction of the capped RNA with protein(s) in the transcriptase complex. Although no specific nucleotide sequence was required for priming activity, capped mRNAs with diminished secondary structure were preferred as primers. Inosine-substituted or bisulfite-modified capped reovirus mRNAs were at least 3- to 5-fold more effective as primers than were the native capped mRNAs. On the other hand, inosine substitution or bisulfite treatment of the uncapped form of reovirus mRNAs converted them from essentially inactive species to potent inhibitors of the transcriptase reaction primed by either ApG or globin mRNA. These effects of reduced secondary structure also most probably reflect an interaction of the exogenous RNAs with transcriptase protein(s). The results obtained from screening a series of native uncapped ribopolymers were consistent with inhibitory activity requiring the absence of most hydrogen bonding in the ribopolymer and also suggested that specific structural feature(s) of the nucleotides in the chain were important.
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PMID:Priming and inhibitory activities of RNAs for the influenza viral transcriptase do not require base pairing with the virion template RNA. 693 19

Influenza viruses, which had lost up to 99.999% infectivity by incubation with antibody (a) specific for the haemagglutinin (HA) or with monoclonal alpha-HA, attached on to and penetrated chick embryo fibroblast (CEF) cells to the same extent as non-neutralized virus. Neutralized virus was also uncoated efficiently as shown by the accumulation of virion RNA in the nucleus and virion envelope in the cytoplasm. Polyacrylamide gel electrophoresis of virion RNA segments recovered from the nucleus or cytoplasm of cells inoculated with neutralized or non-neutralized virus showed that antibody did not potentiate degradation of RNA. However, these RNAs were not expressed since virus-induced proteins were not detected in cells to which neutralized virus had been added. Assay of virion transcriptase of neutralized virus in vitro showed that its activity was reduced up to sevenfold compared with non-neutralized virus, and annealing studies showed that no detectable transcription took place in vivo with neutralized virus. These studies support the conclusion that antibody directed specifically against the HA protein on the outer surface of the influenza virus particle neutralizes infectivity by inactivating virion transcriptase activity and it is suggested that antibody to HA brings about allosteric rearrangements in the HA molecule which are transmitted across the virus envelope to the interior of the particle.
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PMID:Studies on the mechanism of neutralization of influenza virus by antibody: evidence that neutralizing antibody (anti-haemagglutinin) inactivates influenza virus in vivo by inhibiting virion transcriptase activity. 706 92

The effect of 2-[1'-aminoethyl)-bicyclo[2.2.1]heptane chlorohydrate on the accumulation of hemagglutinating activity of chick embryo fibroblasts infected with influenza A/FPV/Rostock/34 (Hav1N1) and A/WSN/33 (H0N1) was studied. The drug inhibited hemagglutinines accumulation when added at various intervals after infection, the maximum effect having been observed upon its addition to the maintenance medium immediately after adsorption. Polyacrylamide gel electrophoresis showed the drug to reduce the synthesis of virus-specific proteins of A/FPV and to inhibit considerably the transcriptase activity of A/FPV and A/WSN viruses in vitro.
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PMID:[Mechanism of action of 2-(1'-aminoethyl)-bicyclo[2.2.1]heptane hydrochloride]. 709 Mar 42


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