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)

We mapped the in vivo phosphorylation sites for the matrix (M) protein of the Orsay and San Juan strains of vesicular stomatitis virus, Indiana serotype, using limited proteolysis and phosphoamino acid analysis. M protein was solubilized from 32P-labeled virions by using detergent and high-salt conditions, then treated with either trypsin or Staphylococcus aureus V8 protease, and analyzed by polyacrylamide gel electrophoresis and autoradiography to determine which fragments contained phosphate residues. The M protein fragment extending from amino acid 20 to the carboxy terminus contained approximately 70% of the control 32P label, while the fragment extending from amino acid 35 to the carboxy terminus had only trace amounts of label. These data indicate that the major phosphorylation site was between amino acids 20 and 34 in the Orsay strain M protein. Phosphoamino acid analysis of M protein by thin-layer electrophoresis showed the presence of phosphothreonine and phosphoserine and that phosphothreonine continued to be released after prolonged vapor-phase acid hydrolysis. These data identify Thr-31 as the primary in vivo phosphate acceptor for M protein of the Orsay strain of vesicular stomatitis virus. The San Juan strain M protein has serine at position 32, which may also be an important phosphate acceptor. In addition, phosphorylation at Ser-2, -3, or -17 occurs to a greater extent in the San Juan strain M protein than in the Orsay strain M protein. The subcellular distribution of phosphorylated M protein was investigated to determine a probable intracellular site(s) of phosphorylation. Phosphorylated M protein was associated primarily with cellular membranes, suggesting phosphorylation by a membrane-associated kinase. Virion M protein was phosphorylated to a greater extent than membrane-bound M protein, indicating that M protein phosphorylation occurs at a late stage in virus assembly. Phosphorylation of wild-type and temperature-sensitive mutant M protein was studied in vivo at the nonpermissive temperature. The data show that phosphorylated M protein was detected only in wild-type virus-infected cells and virions, suggesting that association with nucleocapsids may be required for M protein phosphorylation or that misfolding of mutant M protein at the nonpermissive temperature prevents phosphorylation.
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PMID:Sites of in vivo phosphorylation of vesicular stomatitis virus matrix protein. 132 2

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

Antigenic variants of the New Jersey serotype of vesicular stomatitis virus (VSV-NJ) were isolated and cloned by selecting virus plaques resistant to neutralization by high-titered monoclonal antibodies (MAbs) directed to glycoprotein (G) epitopes V, VI, VII, or VIII. The G proteins of each neutralization-resistant virus variant also exhibited markedly reduced antigenic reactivity with each corresponding epitope-specific MAb as determined by enzyme-linked immuno-absorbent assay and by Western blot analysis. Loss of antigenic reactivity of certain mutant G proteins to a MAb other than the one used to select the mutant virus suggested close antigenic proximity, particularly for epitopes VI and VII. The virion RNAs coding for the entire G gene of the wild-type virus and 10 MAb-induced mutants were sequenced by primer DNA extension using the dideoxy method. Each mutant G gene exhibited only a single nucleotide change, leading in each case to a single amino acid substitution, as follows: Glu210----Lys for all three mutants selected by MAb14 (epitope VII); Pro268----Thr for one mutant selected by MAb12 (epitope VI); Ser277----Lys for all three mutants selected by MAb15 (epitope VIII); and Glu364----Lys for all three mutants selected by MAb11 (epitope V). These neutralizing MAb-selected mutations are clustered in the middle third of the 517-amino acid VSV-NJ G protein, presumably resulting in conformational changes that alter recognition of one or more antigenic determinants by a specific monoclonal antibody.
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PMID:Point mutations in glycoprotein gene of vesicular stomatitis virus (New Jersey serotype) selected by resistance to neutralization by epitope-specific monoclonal antibodies. 245 46

Laboratory and clinical studies on cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, were done. The results obtained are summarized as follows: 1. Absorption and elimination were examined in a total of 5 cases including a case of 10 mg/kg intravenous drip infusion for 30 minutes, 2 cases of 20 mg/kg rapid intravenous injection and 2 cases of 40 mg/kg drip infusion for 30 minutes. Maximum serum levels were attained immediately after drip infusion or rapid injection. Cmax's were 119.2 micrograms/ml for 10 mg/kg, 374.9 micrograms/ml or 255.7 micrograms/ml for 20 mg/kg, and 321.3 micrograms/ml or 431.8 micrograms/ml for 40 mg/kg. These values were determined using an high performance liquid chromatography (HPLC) method. In general, values using the bioassay were higher than those with the HPLC method. T 1/2 (beta)'s were between 1.74 and 1.93 hours using HPLC, and between 1.77 and 2.24 hours using bioassay. Urinary recovery rates were examined in 3 out of 5 cases. Cumulative urinary recovery rates were 57.9-90.6% with HPLC method and 50.4-88.0% with bioassay in a period of 0-8 hours after administration. 2. Clinical efficacy was evaluated in a total of 22 cases including 14 cases of respiratory tract infections, 5 cases of urinary tract infections and 3 cases of cellulitis. Clinical efficacy rate was 95.2%. Bacteriologically, pathogenic organisms were eradicated in 90.0%. As adverse reactions, 1 angular stomatitis, 1 diarrhea and 1 loose stool were noted. Abnormal laboratory test values detected were 1 case of increased GPT and 1 case of increased GOT and GPT.
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PMID:[Laboratory and clinical studies on cefodizime in the pediatric field]. 279 66

The phosphoprotein NS of vesicular stomatitis virus which accumulates within the infected cell cytoplasm is phosphorylated at multiple serine and threonine residues (G. M. Clinton and A. S. Huang, Virology 108:510-514, 1981; Hsu et al., J. Virol. 43:104-112, 1982). Using incomplete chemical cleavage at tryptophan residues, we mapped the major phosphorylation sites to the amino-terminal half of the protein. Analysis of phosphate-labeled tryptic peptides suggests that essentially all of the label is within the large trypsin-resistant fragment predicted from the sequence of Gallione et al. (J. Virol. 39:52-529, 1981). A similar result has been obtained for NS protein isolated from the virus particle by C.-H. Hsu and D. W. Kingsbury (J. Biol. Chem., in press). Analysis of phosphodipeptides utilizing the procedures of C. E. Jones and M. O. J. Olson (Int. J. Pept. Protein Res. 16:135-142, 1980) enabled us to detect as many as six distinct phosphate-containing dipeptides. From these studies, together with the known sequence data, we conclude that the major phosphate residues on cytoplasmic NS protein are located in the amino third of the NS molecule and most probably between residues 35 and 106, inclusive. The studies also provide formal chemical proof that NS protein has a structure consistent with a monomer of the sequence of Gallione et al. as modified by J. K. Rose (personal communication). The low electrophoretic mobility of this protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis is not therefore due to dimerization.
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PMID:Phosphorylation sites on phosphoprotein NS of vesicular stomatitis virus. 298 24

The complete nucleotide sequence of the NS mRNA of vesicular stomatitis virus (New Jersey serotype) was established from two cDNA clones spanning the entire coding region of the mRNA. The gene is 856 nucleotides long and can code for a polypeptide of 274 amino acids. Comparison with the nucleotide sequence of the NS gene of the Indiana serotype revealed only 41% sequence homology. The deduced amino acid sequences of the NS proteins were only 32% homologous, with no identical stretches of more than five amino acids. However, at the C-terminal domain there was a conserved region of 21 amino acids with greater than 90% homology. Surprisingly, relative hydropathicity plots also demonstrated the presence of a large number of hydrophilic amino acids sequestered similarly over the N-terminal half of the protein. In addition, the total number of serine and threonine residues, presumptive phosphorylation sites, was similar and included seven serine and three threonine residues located at identical positions. It appears that during divergent evolution of these two vesicular stomatitis virus serotypes from a common ancestor, considerable mutation occurred in the main body of the gene but the overall structure of the protein was retained. The function of the NS protein in relation to the evolution of the two viruses is discussed.
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PMID:Vesicular stomatitis virus NS proteins: structural similarity without extensive sequence homology. 298 60

Sequences were determined of the coding regions of the M-protein genes of the Glasgow and Orsay strains of vesicular stomatitis virus (Indiana serotype) and of two group III (M-protein) mutants derived from each wild type. Synthetic primers were annealed with viral genomic RNA and extended with reverse transcriptase. The resulting high-molecular-weight cDNA was sequenced directly. Both Glasgow and Orsay wild types differed in 13 bases from a clone of the San Juan strain sequenced by J. K. Rose and C. J. Gallione (J. Virol. 39:519-528, 1981). Six of these base changes caused amino acid changes in each wild type, whereas seven were degenerate. The Orsay and Glasgow sequences resembled each other more closely than either resembled that of Rose and Gallione, differing in eight nucleotides and four amino acids. Each of the four mutants, however, differed from its parent wild type in only one or two point mutations. Every mutation caused a change either from or to a charged amino acid; the change for tsG31 was Lys (position 215) to Glu, the change for tsO23 was Gly (position 21) to Glu, the change for tsO89 was Ala (position 133) to Asp, the changes for tsG33 were Lys (position 204) to Thr and Glu (position 214) to Lys. The charge differences predicted from these amino acid changes was confirmed by nonequilibrium pH gradient electrophoresis for tsG31, tsG33, tsO23, and the two wild types. These mutations affect residues spanning nearly 85% of the linear sequence, although the mutants possess nearly identical phenotypic properties.
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PMID:Sequence alterations in temperature-sensitive M-protein mutants (complementation group III) of vesicular stomatitis virus. 299 21

A full length cDNA copy of the NS mRNA of the Missouri strain (Hazelhurst subtype, New Jersey serotype) of vesicular stomatitis virus (VSV) has been cloned and sequenced. The mRNA is 856 nucleotides long (excluding polyadenylic acid) and encodes a protein of 274 amino acids (mol. wt. 31 000). Comparison with the NS gene of the Ogden strain (Concan subtype, New Jersey serotype) showed 15% difference at the nucleotide level and 10% difference at the amino acid level; the majority of the changes were located in the 3' half of the mRNA. Comparison with the NS genes of two strains representing the Indiana serotype showed about 50% nucleotide and 33% amino acid sequence homology between the serotypes. In a four-way comparison of the proteins, two regions of higher homology were noted which may be of functional importance. Eighteen potential phosphorylation sites (Ser or Thr) were conserved between the four proteins; five of these sites correspond to the residues which have been suggested to be constitutively phosphorylated and may be essential for NS activity.
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PMID:Conservation of potential phosphorylation sites in the NS proteins of the New Jersey and Indiana serotypes of vesicular stomatitis virus. 301 48

The phosphoprotein (NS) gene from the Indiana serotype of vesicular stomatitis virus (VSV; Mudd-Summers strain) was cloned and sequenced. The NS gene encodes a protein of 265 amino acids which was expressed from a simian virus 40 vector in COS cells. The post-translational modification characteristic of viral NS, the extensive phosphorylation of a cluster of serine and threonine residues, was also evident in recombinant NS protein. The NS gene displays a property common to the phosphoprotein genes of negative-strand RNA viruses: the phosphoprotein mRNA has a second open reading frame (ORF) which could encode a small (7500 mol. wt.) protein. Both measles virus and Sendai virus employ the second ORF of their phosphoprotein gene, and the resultant proteins have an amino acid composition similar to that predicted for the VSV ORF. Comparison of phosphoproteins from different VSV strains revealed two conserved domains that we propose are critical for the function of NS in transcription and replication.
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PMID:Cloning and expression of a viral phosphoprotein: structure suggests vesicular stomatitis virus NS may function by mimicking an RNA template. 301 52

The nucleotide sequence of the 3' end of the genome of Chandipura (CHP) virus, including the complete sequences of the nucleocapsid (N) and phosphoprotein (NS) genes was determined, principally from cloned cDNAs of the N and NS mRNAs. The NS mRNA of CHP virus is 908 bases in length and encodes a protein of 293 amino acids. Comparison of the CHP virus NS protein sequence with those of vesicular stomatitis virus of the New Jersey serotype (VSV (NJ)) and of the Indiana serotype (VSV (IND] revealed homologies of only 23 and 21%, respectively, with no consecutive stretches of more than four amino acids identical among the three sequences. As with the two VSV serotypes, the highest homology between the NS proteins of CHP and VSV was in a 20-amino acid region near the carboxy termini of the proteins. Of the potential phosphorylation sites, there are eight conserved serine or threonine residues among the three sequences. Despite the dissimilarity among primary sequences of the NS proteins, their overall structure, as assessed by amino acid composition and by the relative hydropathicities of the sequences, has been conserved throughout evolution. The N mRNA of CHP virus is 1291 bases long and encodes a protein of 422 amino acids. In contrast to the NS protein, the CHP N protein is at least 50% homologous to the N proteins of each of the VSV serotypes. We have identified a region near the center of these N protein sequences which is conserved among members of both the rhabdovirus and paramyxovirus families. This extent of conservation of the N protein sequences underscores the high rate of mutability of the NS protein sequences among the vesiculoviruses.
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PMID:Sequences of Chandipura virus N and NS genes: evidence for high mutability of the NS gene within vesiculoviruses. 302 73


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