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)

A specific endoribonucleolytic activity was detected when detergent-lysed vesicular stomatitis of Sendai virus was incubated with the precursor to Escherichia coli tRNA Tyr. The cleavage products produced and the characteristics of the reaction were similar to those previously reported for human KB cell RNase NU. Like RNase NU, the virus-associated reaction generates 5'-hydroxyl and 3'-phosphate groups at the cleavage sites. At protein concentrations similar to those used to test vesicular stomatitis and Sendai viruses, virions of Sindbis virus and poliovirus also exhibited endoribonucleolytic activity, but reovirus, simian virus 40, and minute virus of mice did not. This endoribonuclease may be of physiological relevance to some of the viruses we tested.
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PMID:Endoribonuclease activity associated with animal RNA viruses. 20 40

The biosynthesis of a secretory protein and a transmembrane viral glycoprotein are compared by two different experimental approaches. (a) NH2-terminal sequence analysis has been performed on various forms of the transmembrane glycoprotein of vesicular stomatitis virus synthesized in cell-free systems. The sequence data presented demonstrate that the nascent precursor of the glycoprotein contains a "signal sequence" of 16 amino acids at the NH2 terminus, whose sequence is Met-Lys-Cys-Leu-Leu-Tyr-Leu-Ala-Phe-Leu-Phe-Ile-(His-Val-Asn)-Cys. This signal sequence is proteolytically cleaved during the process of insertion into microsomal membranes prior to chain completion. The new NH2 terminus of the inserted, cleaved, and glycosylated membrane protein is located within the lumen of the microsomal vesicles and is identical to that of the authentic glycoprotein from virions. (b) Nascent chain competition experiments were performed between this glycoprotein, bovine pituitary prolactin (a secretory protein), and rabbit globin (a cytosolic protein). It was found that the nascent membrane glycoprotein, but not nascent globin, competed with nascent prolactin for membrane sites involved in the early biosynthetic event of transfer across membranes. These data suggest that an initially common pathway is involved in the biogenesis of secretory proteins and at least one class of integral membrane proteins.
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PMID:A signal sequence for the insertion of a transmembrane glycoprotein. Similarities to the signals of secretory proteins in primary structure and function. 21 27

This study describes an analysis of the interaction of individual amino acid residues of the vesicular stomatitis virus (VSV) nucleocapsid antigenic octapeptide (N52-59; Arg-Gly-Tyr-Val-Tyr-Gln-Gly-Leu) with the H-2Kb molecule and T-cell receptors (TCRs). Tyr-3, Tyr-5, and Leu-8 were the positions in the peptide found to be H-2Kb contact residues by analyzing single alanine-substituted peptides in a competition assay with a Kb-restricted antigenic nonapeptide of Sendai virus. Arg-1, Gly-2, Val-4, Gln-6, and Gly-7 of the peptide were identified as putative TCR contact residues by testing the peptide analogs for their capacity to sensitize targets for VSV-specific cytolytic T-lymphocyte clones. The octamer N52-59 was the optimal length of the peptide required for binding to Kb. This peptide length requirement and the finding of an irregular interspersing of major histocompatibility complex and TCR contact residues are most consistent with the conclusion that the peptide is in an extended conformation in the antigen binding groove. Furthermore, data on binding of truncated peptides show that, although the Arg-1 side chain has been assigned as a TCR contact residue, the main-chain atoms of the N-terminal amino group are most likely involved in interacting with the major histocompatibility complex molecule. A panel of H-2Kb point mutants was constructed to explore the effect of altered amino acid residues on the binding of N52-59. Mutants with amino acid substitutions along the floor of the groove all bound the VSV peptide but modulated its interaction with Kb, apparently causing subtle changes in the spatial arrangement of some specific TCR contact residues in the peptide.
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PMID:Vesicular stomatitis virus antigenic octapeptide N52-59 is anchored into the groove of the H-2Kb molecule by the side chains of three amino acids and the main-chain atoms of the amino terminus. 131 83

To study the structure of a homogenous major histocompatibility complex (MHC) class I molecule containing a single bound peptide, a complex of recombinant mouse H-2Kb, beta 2-microglobulin (beta 2m), and a fragment of the vesicular stomatitis virus (VSV) nuclear capsid protein, VSV-(N52-59) octapeptide (Arg-Gly-Tyr-Val-Tyr-Gln-Gly-Leu), was prepared by exploiting a high-yield bacterial expression system and in vitro cocomplex formation. The structure of mouse H-2Kb revealed its similarity to three human class I HLA molecules, consistent with the high primary sequence homology and common function of these peptide-presenting molecules. Electron density was located in the peptide-binding groove, to which a single peptide in a unique conformation was unambiguously fit. The peptide extends the length of the groove, parallel to the alpha-helices, and assumes an extended, mostly beta-strand conformation. The peptide is constrained within the groove by hydrogen bonding of its main-chain atoms and by contacts of its side chains with the H-2Kb molecule. The amino-terminal nitrogen atom of the peptide forms a hydrogen bond with the hydroxyl group of Tyr-171 of H-2Kb at one end of the groove, while the carboxyl-terminal oxygen forms a hydrogen bond with the hydroxyl group of Tyr-84 at the other end. Since the amino acids at both ends are conserved among human and mouse MHC molecules, this anchoring of each end of the peptide appears to be a general feature of peptide-MHC class I molecule binding and imposes restrictions on its length. The side chains of residues Tyr-3, Tyr-5, and Leu-8 of the VSV octapeptide fit into the interior of the H-2Kb molecule with no appreciable surface exposure, a finding in support of previous biological studies that showed the importance of these residues for binding. Thus, the basis for binding of specific peptide sequences to the MHC class I molecule is the steric restriction imposed on the peptide side chains by the architecture of the floor and sides of the groove. The side chains of Arg-1, Val-4, and Gln-6 and the main-chain of Gly-7 of the octapeptide are exposed on the surface of the complex, thus confirming their availability for T-cell receptor contact, as previously demonstrated by T-cell recognition experiments.
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PMID:Crystal structure of the major histocompatibility complex class I H-2Kb molecule containing a single viral peptide: implications for peptide binding and T-cell receptor recognition. 132 57

To define the effects of pp60v-src activity at different intracellular sites, we have constructed chimeric molecules which target the pp60v-src kinase to specific intracellular locations. pp60v-src was targeted to the nucleus by insertion of the SV40 large T antigen nuclear localization signal. Nuclear pp60v-src was active as a tyrosine kinase and phosphorylated nuclear proteins at tyrosine. However, cells expressing the nuclear pp60v-src were phenotypically normal by a number of criteria, and nuclear src kinase did not induce the expression of an mRNA (CEF-4) whose induction is characteristic of transformation by wild-type v-src. pp60v-src was targeted to perinuclear membranes by fusion to rat growth hormone and vesicular stomatitis G protein sequences. Cells expressing this chimeric molecule were phenotypically normal by most criteria. However the perinuclear src protein did induce elevated levels of CEF-4 mRNA, indicating that the v-src kinase expressed at this site induces partial transformation. The v-src and activated c-src kinases were targeted to adhesion plaques by fusion to the talin-binding sequence of vinculin. Cells expressing these fusion proteins were transformed by morphological, physiological and biochemical criteria, although the foci induced by these viruses were distinct from those induced by wild-type v-src. A chimeric protein which targeted c-src to adhesion plaques was not transforming. Thus targeting pp60src to adhesion plaques, although not sufficient to activate the transforming capacity of c-src, is sufficient to allow transformation by v-src.
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PMID:Intracellular targeting of pp60src expression: localization of v-src to adhesion plaques is sufficient to transform chicken embryo fibroblasts. 133 49

A 100 plaque forming unit (pfu) dose of a temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV), tsG31 KS5, engendered a slowly progressive paralytic central nervous system (CNS) disease that killed all BALB/c nude mice within 28 days. Reconstitution of nude mice with 10(7) syngeneic splenocytes 24 h before intracerebral inoculation with tsG31 KS5 VSV, however, protected 92% of the animals from death. When these reconstituted animals were injected intracerebroventricularly with 14 pmol of beta-endorphin 24 h after reconstitution with splenocytes and 24 h before inoculation with tsG31 KS5 VSV, only 72% of the animals survived. Furthermore, whereas 40% of the afflicted reconstituted nude mice given intracerebroventricular injections of sterile water were able to recover from the symptoms of disease, those surviving animals which received beta-endorphin were unable to do so. A single intravenous injection of 14 pmol beta-endorphin, or repeated postinfection administration of 28 pmol of beta-endorphin intravenously into nude mice reconstituted with syngeneic splenocytes, which were pretreated with beta-endorphin, did not alter the course of CNS disease induced by tsG31 KS5 VSV. The effect induced by intracerebroventricular injection of beta-endorphin was antagonized by naloxone, but not by the neuropeptide fragment beta-endorphin-(1-27). A simultaneous intracerebroventricular injection of reconstituted nude mice with 1220 pmol of naloxone and 14 pmol of beta-endorphin resulted in a 89% survival rate, and 33% of the afflicted animals were able to overcome the symptoms of the disease induced by tsG31 KS5 VSV. Intracerebroventricular injection of reconstituted nude mice with 330 pmol of beta-endorphin-(1-27) and 14 pmol of beta-endorphin resulted in a 72% survival rate and the surviving animals were unable to improve appreciably the clinical status of their disease. Injection of reconstituted nude mice with either 1220 pmol of naloxone or 330 pmol of beta-endorphin-(1-27) alone did not alter the course of the CNS disease in any way. A single intracerebroventricular injection of 29 pmol of another psychoactive peptide, [Des-Tyr]-endorphin, 24 h after reconstitution of nude mice with splenocytes and 24 h prior to infection with virus, resulted in 74% survival; and 39% of the afflicted animals were able to recover from the clinical symptoms.
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PMID:Beta-endorphin alters the course of central nervous system disease induced by a temperature-sensitive vesicular stomatitis virus in reconstituted nude mice. 216 Apr 76

Full-length cDNA copies of mRNAs coding for the matrix (M) proteins of vesicular stomatitis virus and its mutant tsO23(III) were cloned in pBSM13- (BlueScribe). The authenticity of these clones was demonstrated by restriction enzyme mapping, DNA sequencing, and in vitro transcription and translation to identify the two M proteins by Western immunoblotting with epitope-specific monoclonal antibodies. Site-directed mutants were constructed by primer extension of synthetic oligodeoxynucleotides with one or two nucleotide changes to alter the glycine at amino acid 21 of the wild-type (wt) M gene to glutamic acid, alanine, or proline. Similarly, a revertant was created in the M gene of mutant tsO23 by a Glu-21----Gly substitution. A series of wt- and mutant-M-gene chimeras was also constructed to create mutant and revertant clones with Leu----Phe and His----Tyr alterations at amino acids 111 and 227, respectively. We then moved the wt and tsO23 M genes and their site-specific mutants and chimeras cloned in pBSM13- into the eucaryotic expression vector pTF7 directed by the T7 bacteriophage RNA polymerase of the vaccinia virus recombinant vTF1-6,2. Western blot analysis of the M proteins transiently expressed in CV-1 cells by plasmids carrying M genes altered at amino acid 21 revealed that the critical antigenic determinant (epitope 1) is expressed only by the Gly-21 M protein and not by Glu-21, Ala-21, or Pro-21 M proteins. Of particular interest is an apparent conformational change, evidenced by slightly but significantly retarded electrophoretic migration, in plasmid-expressed M proteins with amino acids substituted for glycine at position 21. The glutamic acid at position 21 of tsO23 is not responsible for its temperature-sensitive phenotype, because a tsO23 revertant plasmid with glycine substituted at position 21 fails to rescue tsO23 virus in cells infected at the restrictive temperature; conversely, plasmids expressing wt M protein with substitutions of glutamic acid, alanine, or proline at position 21 are just as effective in marker rescue of tsO23 as is the Gly-21 wt M protein. Marker rescue experiments with wt- and mutant-M-gene chimeras support the hypothesis of K. Morita, R. Vanderoef, and J. Lenard (J. Virol. 61:256-263, 1987) that the temperature-sensitive phenotype of tsO23 is due to a phenylalanine substituted for leucine at amino acid 111, rather than the His-227----Tyr substitution or the Gly-21----Glu substitution, which independently accounts for the loss of epitope 1 in the mutant M protein of tsO23.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Site-specific mutations in vectors that express antigenic and temperature-sensitive phenotypes of the M gene of vesicular stomatitis virus. 245 88

We have carried out an exhaustive search for amino acid sequence similarities between vesicular stomatitis virus (VSV) proteins and database entries. Unexpectedly, we found that the L polymerase protein contains two blocks of sequence (residues 725-1102 and 1291-1671) with distant but statistically significant similarity to the catalytic domain of tyrosine-specific protein kinases. The first kinase-like region is most similar to members of the Abl subfamily, Fes and Fps (26.6% and 27.3% identity, respectively), whereas the second region is closest to members of the platelet-derived growth factor receptor (PDGFR) subfamily, PDGFR and Kit (30.4% and 25.9% identity, respectively). Multiple alignment of the catalytic domain of these kinases to all three rhabdovirus L protein sequences available (VSV Indiana, VSV New Jersey, and rabies) revealed that the polymerases contain many but not all residues well conserved in the protein kinase family. Similarity was highest for VSV Indiana and lowest for rabies. We conclude that the kinase-like regions in the rhabdoviral L proteins are probably very distantly related to the protein kinase family. The similarities could either reflect contemporary protein kinase activity or represent some other function(s) associated with these large multifunctional polymerase proteins. Our findings also shed new light on questions of the origins and evolution of RNA viruses.
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PMID:Two domains distantly related to protein-tyrosine kinases in the vesicular stomatitis virus polymerase. 254 20

In this report, we have investigated the contribution of primary sequence to the carbohydrate requirement for intracellular transport of two closely related glycoproteins, the G proteins of the San Juan and Orsay strains of vesicular stomatitis virus. We used site-directed mutagenesis of the coding sequence to eliminate the two consensus sites for glycosylation in the Orsay G protein. Whereas the nonglycosylated San Juan G protein required at least one of its two asparagine-linked oligosaccharides for transport to the plasma membrane at 37 degrees C, a fraction of the Orsay G protein was transported without carbohydrate. Of the 10 amino acid differences between these two proteins, residue 172 (tyrosine in San Juan, aspartic acid in Orsay) played the major role in determining the stringency for the carbohydrate requirement. The rates at which the glycosylated and nonglycosylated Orsay G proteins were transported to the cell surface were the same, although a smaller fraction of the nonglycosylated protein was transported. These results suggest that the carbohydrate does not promote intracellular transport directly but influences a polypeptide folding or oligomerization step which is critical for transport.
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PMID:A single-amino-acid substitution eliminates the stringent carbohydrate requirement for intracellular transport of a viral glycoprotein. 276 Sep 84

We describe the isolation and characterization of conditional lethal amber nonsense mutants of vesicular stomatitis virus (VSV), Indiana serotype. The mutants were isolated from a chemically mutagenized stock of wild-type virus by their ability to grow on genetically engineered cells which express a Xenopus laevis amber suppressor tyrosine tRNA gene (su+ cells) but not on the non-suppressor parental cells (su- cells). Five mutations were assigned to complementation group I (the L gene) and one to complementation group V (the G gene) by complementation analysis using temperature-sensitive mutants representing each of the five VSV cistrons. Four of the group I mutants were observed to synthesize a novel polypeptide species in su+ cells. Immunoprecipitation and immunoblotting studies using monospecific antisera directed against the N and C termini of the VSV L protein showed that the novel polypeptide species contain N terminal- but not C terminal-specific sequences and can thus be considered to be truncated versions of the L protein. In addition a protein which again contained N terminal- but not C terminal-specific sequences could be identified for the fifth group I mutant. Revertants of four of the group I mutants were isolated on the su- cells. The revertants all synthesized normal L protein but not the putative truncated version.
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PMID:Isolation and characterization of conditional lethal amber nonsense mutants of vesicular stomatitis virus. 282 48


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