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 lateral mobility of the vesicular stomatitis virus spike glycoprotein (G protein) and various mutant G proteins produced by site-directed mutagenesis of the G cDNA has been measured. Fluorescence recovery after photobleaching results for the wild type G protein in transfected COS-1 cells yielded a mean diffusion coefficient (D) of 8.5 (+/- 1.3) X 10(-11) cm2/s and a mean mobile fraction of 75% (+/- 3%). Eight mutant proteins were also examined: dTM14, lacking six amino acids from the transmembrane domain; TA2, lacking an oligosaccharide in the extracellular domain; QN2, possessing an extra N-linked oligosaccharide in the extracellular domain; CS2, possessing a serine instead of a cysteine at residue 489 in the cytoplasmic domain, preventing palmitate addition to the glycoprotein; TMR-stop, lacking the entire cytoplasmic domain except an arginine at residue 483; and three chimeric proteins, G mu, G23, and GHA, containing in place of the 29 amino acid wild type cytoplasmic domain the cytoplasmic domains from the surface IgM from the spike protein of the infectious bronchitis virus or from the hemagglutinin protein of the influenza virus, respectively. The mean D for the mutant proteins varied over a relatively small range, with the slowest mutant, G23, exhibiting a value of 11.3 (+/- 1.4) X 10(-11) cm2/s and the fastest mutant, GHA, having a D of 28.6 (+/- 4.5) X 10(-11) cm2/s. The mean mobile fraction similarly varied over a small range, extending from 55 to 68%. None of the mutations resulted in the more rapid diffusion characteristic of membrane proteins embedded in artificial bilayers. Therefore, it appears that the cytoplasmic and transmembrane domains themselves contribute little to restraining the lateral mobility of this integral membrane protein when expressed in transfected cells.
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PMID:Effects of mutations in three domains of the vesicular stomatitis viral glycoprotein on its lateral diffusion in the plasma membrane. 303 31

Intravenous injection of polyinosinic acid/polycytidylic acid [(poly rI).(poly rC)] offered significant protection against intranasal challenge of young mice with vesicular stomatitis virus (VSV). Optimal protection was obtained when a single dose was administered 2 hr before virus challenge, but repeated doses were effective when started as late as 3 days after virus challenge. The therapeutic ratio or ratio of maximum tolerated dose to minimum effective dose for a single intravenous injection of (poly rI).(poly rC) 2 hr before virus inoculation was >/=8 mg/kg:0.004 mg/kg or >/=200.Dose-response curves for interferon production and antiviral protection by (poly rI).(poly rC) were closely parallel. Equivalent doses of poly rI or poly rC alone did not exert any interferon-inducing capacity or protective effect on intranasal VSV challenge. Several factors, which are known to potentiate or antagonize interferon production, increased or decreased the interferon-inducing capacity and antiviral protection of either (poly rI).(poly rC) or maleic acid/divinyl ether copolymer (MA/DVE) in parallel. Interferon production and antiviral protection by MA/DVE were enhanced by arginine but abolished by prior treatment with MA/DVE; DEAE-dextran (intraperitoneally), kinetin riboside and isopentenyladenosine, and prior injection of endotoxin reduced both interferon production and antiviral protection by (poly rI).(poly rC). Treatment with exogenous interferon in amounts which closely mimicked the levels of circulating interferon produced endogenously by an effective dose of (poly rI).(poly rC) gave protection against intranasal VSV which was identical with that dose of (poly rI).(poly rC). This strongly suggests that interferon production accounts for the whole protective effect of (poly rI).(poly rC) in the intranasal VSV assay.
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PMID:The role of interferon in the protective effect of a synthetic double-stranded polyribonucleotide against intranasal vesicular stomatitis virus challenge in mice. 431 83

Inhibitory effects of nitric oxide (NO) on vesicular stomatitis virus (VSV) infection were investigated by using a VSV-susceptible mouse neuroblastoma cell line, NB41A3. Productive VSV infection of NB41A3 cells was significantly inhibited by an organic NO donor, S-nitro-N-acetylpenicillamine (SNAP), while the control compound N-acetylpenicillamine (NAP) had no effect. Survival rate of VSV-infected cells was greatly increased by the treatment with SNAP, while the NAP treatment did not have any effect. Adding SNAP 30 min prior to infection resulted in complete inhibition of viral production when a low multiplicity of infection (MOI) was used. Substantial inhibition of viral production was also obtained with treating cells 6 h earlier before infection with a higher MOI. Activating the neuronal NO synthase by treating cells with N-methyl-D-aspartate (NMDA) led to significant inhibition of viral production by cells infected at the three doses of virus tested (MOIs of 0.1, 1, and 5). The inhibitory effect of NMDA on viral infection was totally blocked by the NO synthase inhibitor N-methyl-L-arginine. However, adding hemoglobin, a strong NO-binding protein and thus an inactivator of NO activity, did not reverse the NMDA-induced inhibition of viral production, suggesting that NO might exert its antiviral effects inside the NO-producing cells. Collectively, these data support the anti-VSV effects of NO, which might be one of the important factors of natural immunity in controlling the initial stages of VSV infection in the central nervous system.
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PMID:Inhibition of vesicular stomatitis virus infection by nitric oxide. 753 52

Our long-term goal is to define the catalytic domains of the L protein subunit of the Sendai virus RNA polymerase. An aberrant polyadenylation phenotype in the vesicular stomatitis virus tsG16 L protein mutant has recently been identified as a phenylalanine to serine change at amino acid 1488 (Hunt and Hutchinson, Virology 193, 786-793, 1993). To test if functional domains are conserved in the L proteins of negative-strand RNA viruses, we attempted to create a similar polyadenylation defect in the Sendai virus L protein. Nine different amino acid substitutions at the analogous site in the Sendai L protein (cysteine at amino acid 1571) were constructed by site-directed mutagenesis of the gene. Each mutant L protein was synthesized and bound to the Sendai P protein to form the P-L polymerase complex. While none of these L mutants exhibited a change in polyadenylation, the single amino acid changes yielded a variety of activities in vitro. Mutants containing valine, leucine, or phenylalanine at amino acid 1571, amino acids found naturally in the L proteins of other paramyxoviruses, yielded polymerases that had biological activity equal to or better than the wild-type (WT) polymerase. Serine or threonine substitutions in the L protein at this position also resulted in polymerases with nearly WT synthetic activity. In contrast, a glycine substitution significantly decreased overall polymerase activity, whereas a tyrosine substitution gave decreased transcription, but virtually no DI genome replication in vitro. The tyrosine-substituted polymerase may be unable to carry out the packaging step of replication, since DI leader RNA synthesis was normal in this mutant. Mutant L proteins with basic arginine or histidine substitutions were inactive in all viral RNA synthesis in vitro, although the polymerase complexes could bind the nucleocapsid template.
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PMID:Alternative amino acids at a single site in the Sendai virus L protein produce multiple defects in RNA synthesis in vitro. 764 61

The purpose of the present study was to analyze the post-translational and activation-dependent modifications of the G protein-coupled thrombin receptor. A human receptor cDNA was engineered to encode an epitope tag derived from the vesicular stomatitis virus glycoprotein at the COOH terminus of the receptor and expressed in human embryonic kidney 293 cells. We show here that the mature receptor is a glycosylated protein with an apparent molecular mass ranging from 68 to 80 kDa by SDS-polyacrylamide gel electrophoresis. Removal of asparagine-linked oligosaccharides with N-glycosidase F leads to the appearance of a 36-40-kDa receptor species. The current model for receptor activation by thrombin involves specific hydrolysis of the arginine-41/serine-42 (Arg-41/Ser-42) peptide bond. Cleavage of the receptor by thrombin was demonstrated directly by Western analyses performed on membranes and glycoprotein-enriched lysates from transfected cells. Whereas thrombin treatment of cells results in increased mobility of the receptor in SDS-polyacrylamide gel electrophoresis, we found that their treatment with the thrombin receptor agonist peptide leads to a decrease in thrombin receptor mobility due, in part, to phosphorylation. The serine proteases trypsin and plasmin also cleave and activate the receptor similar to thrombin, whereas chymotrypsin cleaves the receptor at a site distal to Arg-41, thus rendering it unresponsive to thrombin while still responsive to thrombin receptor agonist peptide.
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PMID:Post-translational and activation-dependent modifications of the G protein-coupled thrombin receptor. 771 46

A class of integral membrane glycoproteins specific to lysosomes has been identified, and they are classified into two separate groups depending on whether or not their cytoplasmic sequence contains a tyrosine residue. Lamp-1 and lamp-2 have a tyrosine-containing motif in their cytoplasmic segments, and this motif was found to direct the glycoproteins to lysosomes. Limp II glycoprotein, on the other hand, lacks a tyrosine in its cytoplasmic segment and it must be directed to lysosomes by a different signal (Fukuda, M. (1991) J. Biol. Chem. 266, 21327-21330). In order to elucidate the targeting signal of Limp II, a cDNA encoding its cytoplasmic segment was fused with a reporter molecule, a chimeric protein of human gonadotropin alpha chain-vesicular stomatitis G-protein transmembrane. After various mutations its expression was examined by immunofluorescence. First it was shown that a chimeric protein with a Limp II wild-type tail is transported to lysosomes. Deletion of the three amino acids of the cytoplasmic tail at the carboxyl terminus abolished this sorting to lysosomes. Substitution of individual amino acids revealed that the Leu-Ile motif in the Leu-Ile-Arg-Thr sequence at the carboxyl terminus is crucial to the sorting signal. When this motif was brought closer to the transmembrane domain by deletion of nine amino acids next to the transmembrane domain, this sorting function was abolished. In addition, substitution of alanine for the serine, which is at 5 residues from the transmembrane also abolished the sorting capacity, although there was no evidence that the phosphorylation of serine is involved in sorting. Altered proteins that were not transported to lysosomes were found to accumulate at the cell surface and, unlike proteins with a wild-type cytoplasmic tail, were unable to undergo endocytosis. These results indicate that the carboxyl-terminal amino acid sequence, including the Leu-Ile motif and the sequence that connects the motif to the transmembrane domain, is critical for the sorting of Limp II to lysosomes.
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PMID:Lysosomal targeting of Limp II membrane glycoprotein requires a novel Leu-Ile motif at a particular position in its cytoplasmic tail. 810 3

Using systematic site-directed mutagenesis, the basolateral targeting signal in the cytoplasmic domain of glycoprotein G from vesicular stomatitis virus (VSV G) has been localized to an 11-amino acid sequence, which contains two essential residues and a third that makes a minor contribution. A tyrosine at position 19 of the 29-residue carboxyl-terminal cytoplasmic tail is the most important residue and cannot be replaced by other aromatic amino acids, while an isoleucine at position 22, 3 residues carboxyl-terminal to this tyrosine, is also critical but can be replaced by other aliphatic residues. Additionally, an arginine at position 16 makes a minor contribution. Therefore the crucial elements of this targeting signal can be represented by the sequence Y-X-X-aliphatic. While earlier investigation has suggested similarity between basolateral targeting and internalization signals, alignment of this sequence with other cytoplasmic targeting signals suggests the existence of a broad class of homologous targeting motifs that direct protein delivery to a variety of cellular locations. This in turn suggests the existence of a family of homologous receptors, distributed throughout the cell, which differ in their affinity for subsets of these targeting sequences.
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PMID:The basolateral targeting signal in the cytoplasmic domain of glycoprotein G from vesicular stomatitis virus resembles a variety of intracellular targeting motifs related by primary sequence but having diverse targeting activities. 819 26

We used photocross-linking of peptides to DnaK to identify elements of the peptide binding site of DnaK. We attached a photoactivatable group (N-hydroxysuccinimidyl-4-azido-salicylic acid (NHS-ASA) or N-iodoacetamidobutyl-4-azido-salicylic acid (I-ABASA)) to different positions on peptide C of the vesicular stomatitis virus glycoprotein, 125I-radiolabeled the cross-linker, cross-linked the peptide to DnaK by UV irradiation, and then determined the amino acid residues of DnaK that were cross-linked to the peptide. Limited trypsin digestion of the DnaK-peptide complex revealed that the derivatives modified with photoactivatable cross-linker peptide C cross-linked to a C-terminal fragment of DnaK and that the N-terminal 45-kDa fragment of DnaK was not cross-linked by these modified peptides. The attachment points of the three peptide C derivatives carrying photoactivatable cross-linkers at different locations on the peptide, PepC-ASA, PepC-S7C-ABASA, and PepC-S8C-ABASA, have been identified as Arg-536, Arg-527, and His-541 of DnaK, respectively. Thus all three peptides cross-linked to amino acids located close together in a sequence that includes one end of the long alpha-helix in the NMR-based secondary structure model of the peptide binding domain of Hsp70 family (Morshauser, R., Wang, H., Flynn, G., and Zuiderweg, E. (1995) Biochemistry 34, 6261-6266).
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PMID:Identification of elements of the peptide binding site of DnaK by peptide cross-linking. 870 69

In cells infected by wild-type (wt) vesicular stomatitis virus (VSV) Indiana, host transcription is severely inhibited. DNA cotransfection studies have implicated the VSV matrix (M) protein in this process (B. L. Black and D. S. Lyles, J. Virol. 66:4058-4064, 1992). The M protein inhibited transcription not only from viral promoters in plasmids but also from the chromosomally integrated human immunodeficiency virus type 1 (HIV-1) provirus promoter (S.-Y. Paik, A. C. Banerjea, G. G. Harmison, C.-J. Chen, and M. Schubert, J. Virol. 69:3529-3537, 1995). In this study, we investigated the effect of wt VSV M protein on expression of a reporter gene under control of a cellular promoter (beta-interferon [IFN-beta] promoter), using double transient transfections in BHK and COS-1 cells. The cellular IFN-beta promoter was as susceptible to the inhibitory effect of the M protein as the viral promoters used previously. Viral proteins N, P, and G had no significant effect on reporter gene expression. The M protein gene from VSV mutant T1026R1, which is defective in host transcription inhibition, was cloned and sequenced, and its effect on reporter gene expression was tested. The mutant M protein had a methionine-to-arginine change at position 51 in the protein sequence and did not inhibit transcription from either the IFN-beta promoter or viral promoters. This VSV mutant is a good inducer of IFN, as opposed to the wt virus, which suppresses IFN induction. These results show that the M protein inhibits transcription from cellular as well as viral promoters and that the M protein does not regulate the IFN promoter any differently from viral promoters. While the M protein may play a role in IFN gene regulation, other viral or cellular factors that provide specificity to the induction process must also be involved.
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PMID:The vesicular stomatitis virus matrix protein inhibits transcription from the human beta interferon promoter. 898 59

The antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV), a member of the family Flaviviridae, were investigated in this study. In vitro, inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine macrophages was correlated to cellular NO production. When cocultured with infected murine neuroblastoma N18 cells, gamma interferon-activated RAW 264.7 cells also efficiently hindered JEV replication in contiguous bystanders, and this anti-JEV effect could be reversed by an NO synthase (NOS) inhibitor, N-monomethyl-L-arginine acetate. In vivo, the mortality rate increased as the NOS activity of JEV-infected mice was inhibited by its competitive inhibitor, N-nitro-L-arginine methyl ester. Moreover, when an organic donor, S-nitro-N-acetylpenicillamine (SNAP), was used, the NO-mediated antiviral effect was also observed in primarily JEV-infected N18, human neuronal NT-2, and BHK-21 cells, as well as in persistently JEV-infected C2-2 cells. These data reaffirm that NO has an effective and broad-spectrum antimicrobial activity against diversified intracellular pathogens. Interestingly, the antiviral effect of NO was not enhanced by treatment of N18 cells with SNAP prior to JEV infection, a measure which has been shown to greatly increase the antiviral effect of NO in infection by vesicular stomatitis virus. From biochemical analysis of the impact of NO on JEV replication in cell culture, NO was found to profoundly inhibit viral RNA synthesis, viral protein accumulation, and virus release from infected cells. The results herein thus suggest that NO may play a crucial role in the innate immunity of the host to restrict the initial stage of JEV infection in the central nervous system.
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PMID:Inhibition of Japanese encephalitis virus infection by nitric oxide: antiviral effect of nitric oxide on RNA virus replication. 918 90


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