Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of two small basic proteins (C and C') encoded by a second open reading frame of the New Jersey serotype of vesicular stomatitis virus (VSV) P gene was reported previously (Spiropoulou and Nichol, J. Virol., 67, 3103-3110, 1993). Here we found that the Indiana serotype virus also expressed C and C' proteins from this reading frame. We eliminated C and C' expression by making a single base change that introduced a stop codon in the C and C' coding sequence, but left the P-protein sequence unchanged. This mutated P gene supported normal replication and packaging of VSV minigenomes encoding G and M proteins. The mutated P gene was also recombined into an infectious clone of VSV that was used to recover virus. The mutant virus no longer expressed the C and C' proteins but showed growth kinetics identical to wild-type virus. The amounts of viral mRNAs and proteins synthesized were indistinguishable in mutant and wild-type virus infected cells as were the yields and composition of mutant and wild-type virus particles. The kinetics of host protein-synthesis shut-off were also identical for both viruses. Although the C and C' proteins were dispensable for VSV growth in tissue culture, they are known to be conserved in all vesiculoviruses, and thus perhaps play a role in viral pathogenesis or transmission by insect vectors.
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PMID:Normal replication of vesicular stomatitis virus without C proteins. 860 60

Phosphorylation by casein kinase II at three specific residues (S-60, T-62, and S-64) within the acidic domain I of the P protein of Indiana serotype vesicular stomatitis virus has been shown to be critical for in vitro transcription activity of the viral RNA polymerase (P-L) complex. To examine the role of phosphorylation of P protein in transcription as well as replication in vivo, we used a panel of mutant P proteins in which the phosphate acceptor sites in domain I were substituted with alanines or other amino acids. Analyses of the alanine-substituted mutant P proteins for the ability to support defective interfering RNA replication in vivo suggest that phosphorylation of these residues does not play a significant role in the replicative function of the P protein since these mutant P proteins supported replication at levels > or = 70% of the wild-type P-protein level. However, the transcription function of most of the mutant proteins in vivo was severely impaired (2 to 10% of the wild-type P-protein level). The level of transcription supported by the mutant P protein (P(60/62/64)) in which all phosphate acceptor sites have been mutated to alanines was at best 2 to 3% of that of the wild-type P protein. Increasing the amount of P(60/62/64) expression in transfected cells did not rescue significant levels of transcription. Substitution with other amino acids at these sites had various effects on replication and transcription. While substitution with threonine residues (P(TTT)) had no apparent effect on transcription (113% of the wild-type level) or replication (81% of the wild-type level), substitution with phenylalanine (P(FFF)) rendered the protein much less active in transcription (< 5%). Substitution with arginine residues led to significantly reduced activity in replication (6%), whereas glutamic acid substituted P protein (P(EEE)) supported replication (42%) and transcription (86%) well. In addition, the mutant P proteins that were defective in replication (P(RRR)) or transcription (P(60/62/64)) did not behave as transdominant repressors of replication or transcription when coexpressed with wild-type P protein. From these results, we conclude that phosphorylation of domain I residues plays a major role in in vivo transcription activity of the P protein, whereas in vivo replicative function of the protein does not require phosphorylation. These findings support the contention that different phosphorylated states of the P protein regulate the transcriptase and replicase functions of the polymerase protein, L.
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PMID:Phosphorylation within the amino-terminal acidic domain I of the phosphoprotein of vesicular stomatitis virus is required for transcription but not for replication. 934 67