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)

All three influenza virus polymerase (P) proteins were expressed in Xenopus oocytes from microinjected in vitro transcribed mRNA analogs, with yields of up to 100 ng per oocyte. To examine the functional state of the Xenopus-expressed P proteins, the polypeptides were tested for their ability to form stable complexes with each other. As seen in virus-infected cells, all three P proteins associated into an immunoprecipitable complex, suggesting that the system has considerable promise for the reconstruction of an active influenza RNA polymerase. Examination of the ability of paired combinations of the P proteins to associate indicated that PB1 contained independent binding sites for PB2 and PA, and so probably formed the backbone of the complex. Sedimentation analysis of free and complexed P proteins indicated that PB1 and PB2 did not exist as free monomers, and that similarly, complexes of all three P proteins did not simply consist of one copy of each protein. The heterodisperse sedimentation rate seen for complexes of all three P proteins did not appear to result from their binding to RNA, suggesting the incorporation of additional polypeptides in the polymerase complex.
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PMID:Complex formation between influenza virus polymerase proteins expressed in Xenopus oocytes. 274 39

The three large RNA segments of influenza C virus C/JJ/50 were cloned and sequenced, and the deduced amino acid sequences were compared with those of the polymerase (P) proteins of influenza A and B viruses. The coding strategy of the C virus RNA segments is the same as that for the large A and B virus segments as one long open reading frame is present in each segment. RNA segment 1 of influenza C virus encodes the equivalent of the PB2 protein; it has an approximate 25% sequence identity with the corresponding (cap binding) influenza A and B virus PB2 proteins. The PB1 protein of influenza C virus, coded for by segment 2, has an approximate 40% sequence identity with the corresponding proteins of influenza A and B viruses including the Asp-Asp sequence motif found in many RNA polymerase molecules. The PB1 polymerase is thus the most highly conserved protein among the influenza A, B, and C viruses. Although the protein coded for by RNA 3 of influenza C virus shows an approximate 25% sequence identity with the acid polymerase (PA) proteins of the A and B viruses, its sequence does not display any acid charge features at neutral pH. This protein is thus referred to as the P3 (rather than the PA) protein of influenza C virus.
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PMID:Comparison of the three large polymerase proteins of influenza A, B, and C viruses. 276 62

Even when neutralized by saturating amounts of monoclonal IgG directed against the haemagglutinin, influenza virus attaches to cells with kinetics similar to those of infectious virus. It then enters those cells and is uncoated; its RNA becomes localized within the nucleus and its lipid envelope and associated proteins remain in the cytoplasm. In this report we show that despite the apparent normality of these early stages of virus-cell interaction, neutralized virus underwent no detectable primary transcription. In contrast, there was only a slight inhibition of transcription by neutralized virus in vitro which was insufficient to account for the loss in infectivity, despite using mRNA to measure the production of capped oligonucleotides or to prime the elongation step. To test whether the absence of primary transcription in vivo resulted from non-accessibility of the genome rather than an effect on the transcriptase complex itself, we examined the susceptibility to RNase of virion RNA after inoculation of cells with neutralized virus. Data clearly show that, unlike RNA of infectious virus, RNA of neutralized virus did not become sensitive to RNase and we conclude that neutralization of influenza virus by IgG results in failure of virus to undergo a secondary uncoating process which is necessary for the activity of the virion transcriptase complex. Finally we show that by treatment of virions in vitro with detergent it is possible to produce a core structure which is stable and has some of the properties expected of a structure resulting from primary uncoating.
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PMID:IgG-neutralized influenza virus undergoes primary, but not secondary uncoating in vivo. 276 31

Using isolated nuclei prepared from influenza virus-infected HeLa cells, factors affecting the synthesis of two species of positive-sense RNA transcripts, i.e., mRNA and cRNA (complementary RNA to vRNA) were analyzed. In the presence of low concentrations of salt, both mRNA and cRNA were synthesized, whereas in the presence of high concentrations of salt, mRNA was synthesized predominantly. Salt-extracts of nuclei (NE) mainly produced cRNA while mRNA was a major product synthesized by salt-treated nuclei (delta N). In the presence of high concentrations of salt, the NE produced mRNA instead of cRNA. After centrifugation of the NE, the precipitates (NEP) predominantly produced mRNA while the supernatant (NES) alone exhibited a low level of cRNA synthesis activity. With the addition of the NES fraction, mRNA synthesis by the NEP was switched to cRNA synthesis. Glycerol gradient centrifugation of the NES fraction in the presence of high salt yielded vRNA-RNA polymerase complexes that catalyzed mRNA synthesis. These observations indicate that a regulatory factor(s) that can be dissociated from vRNA-RNA polymerase complexes upon exposure to high ionic strength is involved in the switch from mRNA to cRNA synthesis. This activity was not detected in nuclear extracts prepared from uninfected cells, suggesting that such a factor(s) is either encoded by the virus genome or induced by virus infection.
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PMID:In vitro synthesis of influenza viral RNA: biochemical complementation assay of factors required for influenza virus replication. 280 17

The two variants of influenza A/Victoria/35/72 (H3N2) virus resistant simultaneously to remantadine, deitiforin, adapromine and amantadine were obtained while passaging the virus in presence of remantadine or deitiforin. Both variants differed from the parental strain in optimal pH for hemolysis, transcriptase activity and in amino acid sequence of M2 protein. Maximal hemolytic activity of the parental strain is registered at pH 5.2, for the variants cultured in the presence of remantadine or deitiforin at pH 5.5 and 5.8, respectively. In contrast to NH4OH, remantadine and deitiforin do not exert inhibition of virus-induced hemolysis. Transcriptase activity of resistant variants is about 50% higher as compared with parental strain (enzyme source--whole virus particles or RNP). The M2 protein of the remantadine variant has 2 amino acid substitutions: 31 (Ser----Asn) and 59 (Met----Leu); the deitiforin variant has 3 substitutions: 14 (Met----Leu), 30 (Ala----Val) and 59 (Met----Leu). The phenotypic resistance of the virus seems to be determined by the mutations in the hydrophobic protein region (30,31); the other substitutions (14,59) may modify conformational structure and functional activity of the viral proteins.
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PMID:[The change in functional activity and primary structure of the M2 protein in variants of the influenza virus resistant to remantadine and deitiforin: common and individual differences from the original strain]. 281

The M2 protein of influenza A virus is a small integral membrane protein of 97 residues that is expressed on the surface of virus-infected cells. M2 has an unusual structure as it lacks a cleavable signal sequence yet contains an ectoplasmic amino-terminal domain of 23 residues, a 19 residue hydrophobic transmembrane spanning segment, and a cytoplasmic carboxyl-terminal domain of 55 residues. Oligonucleotide-mediated deletion mutagenesis was used to construct a series of M2 mutants lacking portions of the hydrophobic segment. Membrane integration of the M2 protein was examined by in vitro translation of synthetic mRNA transcripts prepared using bacteriophage T7 RNA polymerase. After membrane integration, M2 was resistant to alkaline extraction and was converted to an Mr approximately equal to 7,000 membrane-protected fragment after digestion with trypsin. In vitro integration of M2 requires the cotranslational presence of the signal recognition particle. Deletion of as few as two residues from the hydrophobic segment of M2 markedly decreases the efficiency of membrane integration, whereas deletion of six residues completely eliminates integration. M2 proteins containing deletions that eliminate stable membrane anchoring are apparently not recognized by signal recognition particles, as these polypeptides remain sensitive to protease digestion, indicating that in addition they do not have a functional signal sequence. These data thus indicate that the signal sequence that initiates membrane integration of M2 resides within the transmembrane spanning segment of the polypeptide.
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PMID:Integration of a small integral membrane protein, M2, of influenza virus into the endoplasmic reticulum: analysis of the internal signal-anchor domain of a protein with an ectoplasmic NH2 terminus. 283 32

Acidic chloroform-methanol soluble proteins possessing hydrophobic properties and capable of inhibiting in vitro transcriptase activity of influenza virus RNP were detected in native and partially purified human leukocyte interferon (IFN) preparations. Purification of IFN resulted in the removal of at least a portion of such proteins; however, no proteins have been found in highly-purified IFN preparations.
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PMID:Studies of proteins soluble in acidic chloroform-methanol isolated from crude human leukocyte interferon preparations. 286 58

All rimantadine-resistant variants of influenza virus prepared by consecutive passages in the presence of rimantadine had increased virion transcriptase activity as compared to the original strains. The increased virion transcriptase activity of rimantadine-resistant strains was unrelated to the possible role of M1 protein, since RNPs isolated from the virions of these variants also revealed higher transcriptase activity as compared to RNPs isolated from rimantadine-sensitive virus. The study of rimantadine-resistant recombinant X-4 which inherited from the resistant fowl plague virus (FPV) only the gene 7 coding for M proteins provided additional evidence for the suggestion that the increased virion transcriptase activity of rimantadine-resistant influenza virus variants is coincidental rather than directly associated with such resistance.
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PMID:Virion transcriptase activity of rimantadine-sensitive and rimantadine-resistant variants of human influenza virus. 289 38

Immunogold labelling and in vitro transcription of influenza virus vRNA have been used to analyse the interaction of anti-influenza polymerase antibodies with influenza-ribonucleoprotein (RNP) complexes. The polymerase proteins (P proteins) were localized exclusively at one end of the RNP segments. In the course of transcription the amount of P protein decreased significantly. The in vitro transcriptase activity y of influenza A virus RNP complexes in the presence of anti-polymerase antibodies to the strain A/PR/8/34 was inhibited by 60%. In contrast, RNP transcriptase activity of influenza B virus was not inhibited by these antibodies.
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PMID:Interaction between anti-influenza viral polymerase antibodies and RNP particles using the in vitro transcription process and an immunogold labelling technique. 290 34

Mono- and bisthiopyrophosphate can inhibit the replication of influenza virus A/X49 in Madin-Darby canine kidney (MDCK) cells at concentrations at which no cytotoxic effect is observed after 3 days. The thiopyrophosphate analogues inhibit the RNA transcriptase activity of this virus possibly by chelating with an essential metal ion in the transcriptase complex. [31P]NMR spectroscopy indicates that bisthiopyrophosphate coordinates to zinc through sulphur and magnesium through oxygen which may influence the inhibitory properties of this compound with metal-containing enzymes.
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PMID:Thio-analogues of inorganic pyrophosphate inhibit the replication of influenza virus A in vitro. 299 Mar 33


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