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)

The avian viral agent S1133 has previously been classified serologically as a member of the avian reovirus group. This viral agent grows in chicken embryo fibroblast cells, bands at a density of 1.37 g/ml in CsCl equilibrium density gradients, has a particle diameter of 75 nm, and has a morphology similar to that of human reovirus type 3. Its nucleic acid is comprised of double-stranded RNA and adenosine-rich oligonucleotides. The dsRNA is distributed among 10 segments with molecular weights of 2.7 x 10(6), 2.6 x 10(6), 1.7 x 10(6), 1.5 x 10(6), 1.3 x 10(6), 1.2 x 10(6), 0.80 x 10(6), 0.74 x 10(6), and 0.68 x 10(6) for the largest (L1) to the smallest (S4) segment, respectively, as determined by polyacrylamide gel electrophoresis. These 10 segments migrate differently on polyacrylamide gels compared to those of human reovirus type 3. The capsid proteins of avian reovirus consist of eight species of polypeptides as determined by polyacrylamide gel electrophoresis. These are lambda1, lambda2, lambda3, mu1, mu2, sigma1, sigma2, and sigma3 with molecular weights of 140, 125, 115, 85, 72, 40, 36, and 32 x 10(3), respectively. Only polypeptide sigma2, which resides in the inner capsid or core, comigrated with the sigma2 polypeptide of type 3 reovirus. Antiserum against type 3 reovirus did not neutralize avian reovirus. Avian reovirus core particles were found to possess a transcriptase and a methylase activity.
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PMID:Physical and chemical characterization of an avian reovirus. 98 52

A newly identified temperature-sensitive mutant whose defect was mapped to the reovirus M1 gene (minor core protein mu2) was studied to better understand the functions of this virion protein. Sequence determination of the Ml gene of this mutant (tsH11.2) revealed a predicted methionine-to-threonine alteration at amino acid 399 and a change from proline to histidine at amino acid 414. The mutant made normal amounts of single-stranded RNA, both in in vitro transcriptase assays and in infected cells, and normal amounts of progeny viral protein at early times in a restrictive infection. However, tsH11.2 produced neither detectable progeny protein nor double-stranded RNA at late times in a restrictive infection. These studies indicate that mu2 plays a role in the conversion of reovirus mRNA to progeny double-stranded RNA.
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PMID:Identification and characterization of a double-stranded RNA- reovirus temperature-sensitive mutant defective in minor core protein mu2. 867 44

The mammalian Orthoreovirus (mORV) core particle is an icosahedral multienzyme complex for viral mRNA synthesis and provides a delimited system for mechanistic studies of that process. Previous genetic results have identified the mORV mu2 protein as a determinant of viral strain differences in the transcriptase and nucleoside triphosphatase activities of cores. New results in this report provided biochemical and genetic evidence that purified mu2 is itself a divalent cation-dependent nucleoside triphosphatase that can remove the 5' gamma-phosphate from RNA as well. Alanine substitutions in a putative nucleotide binding region of mu2 abrogated both functions but did not affect the purification profile of the protein or its known associations with microtubules and mORV microNS protein in vivo. In vitro microtubule binding by purified mu2 was also demonstrated and not affected by the mutations. Purified mu2 was further demonstrated to interact in vitro with the mORV RNA-dependent RNA polymerase, lambda3, and the presence of lambda3 mildly stimulated the triphosphatase activities of mu2. These findings confirm that mu2 is an enzymatic component of the mORV core and may contribute several possible functions to viral mRNA synthesis.
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PMID:Nucleoside and RNA triphosphatase activities of orthoreovirus transcriptase cofactor mu2. 1461 38

Mycophenolic acid (MPA), an inhibitor of IMP dehydrogenase, inhibits reovirus replication and viral RNA and protein production. In mouse L929 cells, antiviral effects were greatest at 30 microg of MPA/ml. At this dosage, MPA inhibited replication of reovirus strain T3D more than 1,000-fold and inhibited replication of reovirus strain T1L nearly 100-fold, compared to non-drug-treated controls. Genetic reassortant analysis indicated the primary determinant of strain-specific differences in sensitivity to MPA mapped to the viral M1 genome segment, which encodes the minor core protein mu2. MPA also inhibited replication of both strains of reovirus in a variety of other cell lines, including Vero monkey kidney and U373 human astrocytoma cells. Addition of exogenous guanosine to MPA-treated reovirus-infected cells restored viral replicative capacity to nearly normal levels. These results suggest the mu2 protein is involved in the uptake and processing of GTP in viral transcription in infected cells and strengthens the evidence that the mu2 protein can function as an NTPase and is likely a transcriptase cofactor.
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PMID:Inhibition of reovirus by mycophenolic acid is associated with the M1 genome segment. 1516 10

We report the first sequence analysis of the entire complement of M-class genome segments of an avian reovirus (ARV). We analyzed the M1, M2 and M3 genome segment sequences, and sequences of the corresponding muA, muB and muNS proteins, of two virus strains, ARV138 and ARV176. The ARV M1 genes were 2,283 nucleotides in length and predicted to encode muA proteins of 732 residues. Alignment of the homologous mammalian reovirus (MRV) mu2 and ARV muA proteins revealed a relatively low overall amino acid identity ( approximately 30%), although several highly conserved regions were identified that may contribute to conserved structural and/or functional properties of this minor core protein (i.e. the MRV mu2 protein is an NTPase and a putative RNA-dependent RNA polymerase cofactor). The ARV M2 genes were 2158 nucleotides in length, encoding predicted muB major outer capsid proteins of 676 amino acids, more than 30 amino acids shorter than the homologous MRV mu1 proteins. In spite of the difference in size, the ARV/MRV muB/mu1 proteins were more conserved than any of the homologous proteins encoded by other M- or S-class genome segments, exhibiting percent amino acid identities of approximately 45%. The conserved regions included the residues involved in the maturation- and entry- specific proteolytic cleavages that occur in the MRV mu1 protein. Notably missing was a region recently implicated in MRV mu1 stabilization and in forming "hub and spokes" complexes in the MRV outer capsid. The ARV M3 genes were 1996 nucleotides in length and predicted to encode a muNS non-structural protein of 635 amino acids, significantly shorter than the homologous MRV muNS protein, which is attributed to several substantial deletions in the aligned ARV muNS proteins. Alignments of the ARV and MRV muNS proteins revealed a low overall amino acid identity ( approximately 25%), although several regions were relatively conserved.
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PMID:Sequences of avian reovirus M1, M2 and M3 genes and predicted structure/function of the encoded mu proteins. 1629 81