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)

Recently accumulated knowledge allows more precise comparison of the structural (and possibly evolutionary) relationships of several different animal rhabdoviruses: vesicular stomatitis virus, rabies virus, Kern Canyon virus, and spring viremia of carp virus. Each virus is composed primarily of a glycoprotein, an RNA-associated nucleoprotein, and one or two membrane proteins. Vesicular stomatitis virus group viruses contain lesser amounts of two additional distinct polypeptides, NS and L. The separate viruses undergo structural polypeptide phosphorylation in vivo according to characteristic patterns. In vesicular stomatitis virus the NS protein is selectively phosphorylated. In rabies group viruses and in spring viremia of carp virus, the nucleoprotein is the predominant phosphoprotein; in these viruses only the phosphorylated moiety is selectively cleaved off with trypsin. In Kern Canyon virus, only membrane protein and glycoprotein are weakly phosphorylated. Each virus possesses a virion-bound protein kinase. Vesicular stomatitis virus group viruses, Kern Canyon virus, and spring viremia of carp virus only contain virion-bound transcriptases of respectively decreasing levels of activity demonstrable in vitro. Vesicular stomatitis and Kern Canyon viruses replicate efficiently in enucleated cells; rabies virus does not. Based upon these observations, it is suggested that vesicular stomatitis virus may represent the most highly evolved of these rhabdoviruses, whereas spring viremia of carp and Kern Canyon viruses may represent "evolutionary links" between the vesicular stomatitis and rabies virus groups.
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PMID:Structure-function relationships and mode of replication of animal rhabdoviruses. 16 94

This study of the physico-chemical properties of bovine ephemeral fever virus was initiated to establish whether or not it should be classified as a rhabdovirus. In contrast to the regular bullet-shaped morphology of some rhabdoviruses the virus particles are often cone-shaped or slight variants from bullet-shaped. The virion contains single-stranded RNA sedimenting at 42S and six proteins with mol. wt. of 164, 101, 64, 53, 43 and 29 x 10(3). The protein P101 is located on the surface of the virus and is glycosylated. It is removed by treatment of the virus particles with trypsin. Protein P64, the nucleoprotein, was found to be a phosphoprotein, like the N protein of rabies virus, whereas in vesicular stomatitis virus NS is the phosphorylated protein. Virus harvests contain defective-interfering particles. The particles are short cone-shaped forms about one-third the length of the infectious virion and similar in morphology to defective-interfering particles of vesicular stomatitis virus. These particles interfere with the replication of bovine ephemeral fever virus but not with the Indiana serotype of vesicular stomatitis virus. They contain single-stranded RNA sedimenting at 18 to 20S. The particles appear to have a protein composition identical to that found in the virus particle. The physico-chemical properties of bovine ephemeral fever virus justify its inclusion in the family Rhabdoviridae. The protein composition differs in detail from that found for vesicular stomatitis and rabies viruses, but is similar to that found for Obodhiang and kotonkan, two rabies serogroup viruses isolated from insects in Africa.
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PMID:The physico-chemical characterization of bovine ephemeral fever virus as a member of the family Rhabdoviridae. 50 40

The phosphoprotein (P) and the large protein (L) constitute the RNA-dependent RNA polymerase of vesicular stomatitis virus (VSV). We show that phosphate-free P protein expressed in bacteria is transcriptionally inactive when reconstituted with L protein and viral N-RNA template free of cellular protein kinase. Phosphorylation of P protein by a cellular kinase(s) was essential for transcription as well as for further phosphorylation by an L-associated kinase, the two kinases acting in a sequential (cascade) manner. Phosphate groups introduced by cell kinase were stable, whereas those due to L kinase underwent a turnover which was coupled to ongoing transcription. We present a model for the phosphorylation pathway of P protein and propose that continued phosphorylation and dephosphorylation of P protein may represent a transcriptional regulatory (on-off) switch of nonsegmented negative-strand RNA viruses.
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PMID:Sequential phosphorylation of the phosphoprotein of vesicular stomatitis virus by cellular and viral protein kinases is essential for transcription activation. 130 93

Encapsidation of presynthesized and nascent (synthesized de novo) vesicular stomatitis virus (VSV) leader RNA in vitro by the nucleocapsid protein (N) and the role of the phosphoprotein (P, previously known as NS) in this process were examined. Presynthesized VSV leader RNAs were derived from the SP6 transcription vectors containing both (+) and (-) leader genes while the nascent RNA was derived from transcription of viral ribonucleoprotein (RNP) complex. The N and the P proteins were made by transcription from SP6 vectors containing the genes, followed by translation of the mRNAs in rabbit reticulocyte lysate. Here, we demonstrate that the N protein alone encapsidated presynthesized VSV leader RNA; however, prior formation of N-P complex totally abolished the encapsidation property of N. On the other hand, encapsidation of nascent RNA by the N protein was stimulated by the N-P complex. These results suggest that encapsidation by the N protein of presynthesized and nascent VSV RNA are separate biochemical processes which can be distinguished by the differential role of the phosphoprotein P in the two reactions.
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PMID:Role of the phosphoprotein (P) in the encapsidation of presynthesized and de novo synthesized vesicular stomatitis virus RNA by the nucleocapsid protein (N) in vitro. 131 45

We have previously shown that phosphorylation of vesicular stomatitis virus (VSV) phosphoprotein P by cellular protein kinase activity is an essential prerequisite for its transcriptional function. We have now purified this protein kinase by monitoring its ability to phosphorylate bacterially expressed, unphosphorylated P protein. Biochemical studies showed that the kinase is indistinguishable from casein kinase II, a ubiquitous cyclic AMP-independent protein kinase present in a wide variety of eukaryotic cells and tissues. Functional VSV transcription could be reconstituted with viral L protein, N-RNA template, and P protein phosphorylated by either purified cellular protein kinase or purified casein kinase II. The unusual role of casein kinase II in the transcription process of a nonsegmented negative-strand RNA virus would have important implications in host-virus interactions and antiviral therapy.
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PMID:Phosphorylation by cellular casein kinase II is essential for transcriptional activity of vesicular stomatitis virus phosphoprotein P. 132 44

The phosphorylated state of the vesicular stomatitis virus phosphoprotein (P), an essential component of the virion-associated RNA polymerase complex, has been shown to be important for the transcriptional activity of the complex. Recent studies indicate that phosphorylation within the acidic domain of the P protein by cellular casein kinase II is necessary for its activity. In an attempt to identify the exact location of the cell kinase-mediated phosphorylation, we altered specific serine and threonine residues within the acidic domain of the New Jersey serotype of P protein by site-directed mutagenesis. The altered P proteins were then tested to determine what effect these mutations had on the phosphorylated state of the protein in vivo as well as its transcriptional activity in vitro. We report that serine residues 59 and 61 within the acidic domain of the P protein must be phosphorylated for it to be functionally active in a reconstituted transcription assay. These results demonstrate the importance of site-specific phosphorylation in the transcriptional activity of a negative-strand RNA viral phosphoprotein and the crucial role played by a cell protein kinase in this process.
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PMID:Phosphorylation of specific serine residues within the acidic domain of the phosphoprotein of vesicular stomatitis virus regulates transcription in vitro. 132 45

As part of a study of transcriptional regulation by viral proteins, we examined whether an acidic region from a regulatory protein of an RNA virus could function as a trans-activator. The NH2-terminal highly acidic domain I of the phosphoprotein (P) of vesicular stomatitis virus (VSV) was fused to the DNA-binding domain of the yeast trans-activator, GAL4. In transient transfection assays, the resulting chimeric protein failed to activate transcription of a reporter CAT gene. However, mutation of basic amino acid residues located at positions 6 and 8 or the alteration of eight amino acids within the acidic domain to eight different amino acids converted the chimeric protein into a transcriptional activator comparable to wild-type GAL4. When subjected to SDS-polyacrylamide gel electrophoresis, the P proteins containing trans-activation-positive mutations in domain I showed an altered mobility, suggesting that these mutations may have caused a conformational change that is critical for trans-activation. Since the acidity of P domain I is not sufficient to activate transcription, additional features of this region must play an important role in GAL4-mediated trans-activation. None of the trans-activation-positive mutants supported VSV RNA transcription in vitro. These results suggest that the amino acid residues within P domain I that can be made to function in the trans-activation of DNA-dependent RNA transcription are distinct from those involved in VSV RNA-dependent RNA transcription.
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PMID:Alteration of specific amino acid residues in the acidic domain I of VSV phosphoprotein (P) converts a GAL4-P(I) hybrid into a transcriptional activator. 165 11

An alternative approach to structure-function analysis of vesicular stomatitis virus (VSV) gene products and their interactions with one another during each phase of the viral life cycle is described. We showed previously by using the vaccinia virus-T7 RNA polymerase expression system that when cells expressing the nucleocapsid protein (N), the phosphoprotein (NS), and the large polymerase protein (L) of VSV were superinfected with defective interfering (DI) particles, rapid and efficient replication and amplification of (DI) particle RNA occurred. Here, we demonstrate that all five VSV proteins can be expressed simultaneously when cells are contransfected with plasmids containing the matrix protein (M) gene and the glycoprotein (G) gene of VSV in addition to plasmids containing the genes for the N, NS, and L proteins. When cells coexpressing all five VSV proteins were superinfected with DI particles, which because of their defectiveness are unable to express any viral proteins or to replicate, DI particle replication, assembly, and budding were observed and infectious DI particles were released into the culture fluids. Omission of either the M or G protein expression resulted in no DI particle budding. The vector-supported DI particles were similar in size and morphology to the authentic DI particles generated from cells coinfected with DI particles and helper VSV and their infectivity could be blocked by anti-VSV or anti-G antiserum. The successful replication, assembly, and budding of DI particles from cells expressing all five VSV proteins from cloned cDNAs provide a powerful approach for detailed structure-function analysis of the VSV gene products in each step of the replicative cycle of the virus.
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PMID:Cells that express all five proteins of vesicular stomatitis virus from cloned cDNAs support replication, assembly, and budding of defective interfering particles. 184 19

The phosphoprotein (P, previously known as NS) genes of vesicular stomatitis virus serotypes New Jersey and Indiana have been cloned in the Escherichia coli expression vector pET-3a. Transcription of P genes in these clones initiated from a phage T7 RNA polymerase promoter, whereas translation was driven by the Shine-Dalgarno sequence and the initiator AUG codon of the T7 gene 10 message. The clones were introduced into an appropriate E. coli strain in which T7 RNA polymerase was expressed under the control of the lac promoter. Under optimal conditions of induction with isopropylthiogalactopyranoside, P protein made in these bacterial strains constituted 5 to 20% of total cellular protein. P protein expressed in bacteria was unphosphorylated and transcriptionally active in an in vitro reconstitution assay with viral L protein and an N-RNA template. However, the P protein was phosphorylated in vitro by the kinase activities associated with L and the N-RNA template.
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PMID:Cloning and expression of the vesicular stomatitis virus phosphoprotein gene in Escherichia coli: analysis of phosphorylation status versus transcriptional activity. 184 4

The entire phosphoprotein (P) and nucleocapsid (N) protein gene sequences and deduced amino acid sequences for 18 selected vesicular stomatitis virus isolates representative of the natural genetic diversity within the New Jersey serotype are reported. Phylogenetic analysis of the data using maximum parsimony allowed construction of evolutionary trees for the individual genes and the combined N, P, and glycoprotein (G) genes of these viruses. Virtually identical rates of nucleotide substitutions were found for each gene, indicating that evolution of these genes occurs at essentially the same rate. Although up to 19 and 17% sequence differences were evident in the P and N genes, respectively, no variation in gene length or evidence of recombinational rearrangements was found. However, striking evolutionary differences were observed among the amino acid sequences of vesicular stomatitis virus New Jersey N, P, and G proteins. The N protein amino acid sequence was the most highly conserved among the different isolates, indicating strong functional and structural constraints. Conversely, the P protein amino acid sequences were highly variable, indicating considerably fewer constraints or greater evolutionary pressure on the P protein. Much of the remarkable amino acid variability of the P protein resided in a hypervariable domain located between amino acids 153 and 205. The variability within this region would be consistent with it playing a structural role as a spacer to maintain correct conformational presentation of the separate active domains of this multifunctional protein. In marked contrast, the adjacent domain I of the P protein (previously thought to be under little evolutionary constraint) contained a highly conserved region. The colocalization of a short, potentially functional overlapping open reading frame to this region may explain this apparent anomaly.
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PMID:Phosphoprotein and nucleocapsid protein evolution of vesicular stomatitis virus New Jersey. 215 27


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