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 matrix (M) protein of vesicular stomatitis virus (VSV) has a major antigenic determinant (epitope 1) that maps to a region extending from amino acids 19 through 43 and transcription-inhibition activity that maps to the first 43 N-terminal amino acids (J.R. Ogden, R. Pal, and R. R. Wagner, J. Virol. 58:860-868, 1986). The M protein of temperature-sensitive mutant tsO23(III) is devoid of epitope 1 and transcription-inhibition activity and substitutes glutamic acid for glycine at amino acid 21 as well as having amino acid substitutions at positions 111 and 227 (K. Morita, R. Vanderoef, and J. Lenard, J. Virol. 61:256-263, 1987). We undertook to map more precisely epitope 1 and the transcription-inhibition region of VSV M protein by means of synthetic oligopeptides generated by an automated solid-phase protein synthesizer. A pentadecapeptide designated PI(wt, Gly21), corresponding to amino acids 17 to 31 of wild-type (wt) M protein, strongly bound monoclonal antibody MAb2 (directed to epitope 1); however, an analogous pentadecapeptide with glutamic acid substituted for glycine at position 21, designated PII(tsO23, Glu21), completely failed to recognize MAb2. Polyclonal antibody raised in rabbits immunized with PI(wt, Gly21) reacted strongly with wt M protein, the homologous pentadecapeptide, and, to a lesser extent, PII(tsO23, Glu21). Anti-PII(tsO23, Glu21) failed to recognize PI(wt, Gly21) or wt M protein. Anti-PI(wt, Gly21) competed efficiently for binding of MAb2 to wt M protein and was as effective as MAb2 in reversing inhibition of VSV transcription by wt M protein. Neither PI(wt, Gly21) nor PII(tsO23, Glu21) exhibited any ability to inhibit VSV transcription. However, a lysine-rich oligopeptide, PII(Met1-Leu20), corresponding to the first 20 N-terminal amino acids of wt M protein, and polylysine itself did inhibit VSV transcription, albeit much less efficiently than native wt M protein. Monospecific polyclonal antibody directed to the 20-mer oligopeptide PIII(Met1-Leu20) reversed transcription inhibition by M protein in a dose-dependent manner almost identical to that of anti-PI(wt, Gly21) and epitope 1-specific MAb2. Examination by circular dichroism spectropolarimetry revealed significant differences in the conformation of the two pentadecapeptides attributable to the Gly in equilibrium Glu amino acid substitution at position 21.
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PMID:Antigenicity, function, and conformation of synthetic oligopeptides corresponding to amino-terminal sequences of wild-type and mutant matrix proteins of vesicular stomatitis virus. 283 87

Phosphorylation of membrane-associated proteins by protein kinases in the membrane fraction from HeLa S3 cells was rapidly increased when the cells were infected with vesicular stomatitis virus (VSV). SDS-PAGE followed by autoradiography revealed polypeptides with molecular sizes of Mr. 53,000, 44,000, 42,000, 35,000, 30,000 and 27,000 in the kinase fraction from uninfected cells to be highly phosphorylated. Virus-coding NS protein (Mr. 40,000) was phosphorylated when the membrane fraction from virus-infected cells was incubated with [gamma-32P]ATP in the presence of histone H1 and Mg2+. Under these conditions, histone H1 functioned as a stimulator for NS protein phosphorylation by the kinases. One (kinase III) of the membrane-associated kinases was partially purified from HeLa S3 cells using FPLC (type Mono Q) after DEAE-cellulose column chromatography. The enzymatic properties of kinase III were similar to those reported for a polypeptide-dependent protein kinase (protein kinase P), because (a) both kinases highly phosphorylated beta-casein, although no phosphorylation was observed with histones; (b) several endogenous substrates from HeLa S3 cell membrane were phosphorylated by the kinases in the presence of basic proteins, such as histones, protamine and poly-Lys; (c) their activity was insensitive to a low concentration (19 micrograms/ml) of heparin, which highly inhibited casein kinase II activity; and (d) the kinases were extractable from the plasma membrane using Triton X-100. In addition, provided evidence suggests that kinase III may play an important role in an early stage of VSV replication through its specific phosphorylation of NS protein and membrane proteins in virus infected cells.
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PMID:Characterization of a polypeptide-dependent membrane protein kinase that specifically phosphorylates NS protein of vesicular stomatitis virus in vitro. 284 89

Short (14 to 20-mer range) synthetic oligodeoxyribonucleotides (oligos) allow to modulate specifically viral or cellular gene expression at various stages thus providing a versatile tool for fundamental studies and a rational approach to antiviral chemotherapy. Several problems, such as metabolic stability and efficient cell internalization of oligos, still limit this approach appreciably, as briefly discussed here. We demonstrate here that the conjugation of 15-mer (beta)-anomeric oligos to poly(L-lysine) allows a specific protection of various cell lines against vesicular stomatitis virus infection at concentrations lower than 1 microM. This can be achieved with oligos complementary to the viral N-protein mRNA initiation site or to viral intergenic sequences, i.e., to untranscribed regions. No antiviral activity can be obtained with (alpha)-anomeric oligos directed against the same targets, although such analogues are much more resistant to nuclease degradation and form stable hybrids, at least in cell-free experiments.
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PMID:Antiviral activity of conjugates between poly(L-lysine) and synthetic oligodeoxyribonucleotides. 285 89

A peptide corresponding to the amino-terminal 25 amino acids of the mature vesicular stomatitis virus glycoprotein has recently been shown to be a pH-dependent hemolysin. In the present study, we analyzed smaller constituent peptides and found that the hemolytic domain resides within the six amino-terminal amino acids. Synthesis of variant peptides indicates that the amino-terminal lysine can be replaced by another positively charged amino acid (arginine) but that substitution with glutamic acid results in the total loss of the hemolytic function. Peptide-induced hemolysis was dependent upon buffer conditions and was inhibited when isotonicity was maintained with mannitol, sucrose, or raffinose. In sucrose, all hemolytic peptides were also observed to mediate hemagglutination. The large 25-amino acid peptide is also a pH-dependent cytotoxin for mammalian cells and appears to effect gross changes in cell permeability. Conservation of the amino terminus of vesicular stomatitis virus and rabies virus suggests that the membrane-destabilizing properties of this domain may be important for glycoprotein function.
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PMID:Biologically active peptides of the vesicular stomatitis virus glycoprotein. 298 56

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

Molecular hybrids were synthesized by coupling (2'-5')(A)n oligoadenylates or 2-5A, an intracellular mediator involved in antiviral activity of interferons (IFNs), with poly(L-lysine) used as a membrane carrier. (2'-5')(A)n in its free form was not taken up by cells, probably because of its ionic character. Conjugation with the polypeptide carrier overcame this problem and enabled its pharmacological properties to be developed. The alpha-glycol group of individual (2'-5')(A)n oligomers was oxidized by periodate oxidation and conjugated by an amino reductive reaction to poly(L-lysine), Mr 14 000, in a molar ratio of 5:1. These hybrid molecules left the biologically active 5' end moiety of the (2'-5')(A)n molecule unchanged, and in particular its triphosphate group, and stabilized the molecule by increasing its resistance to phosphodiesterase hydrolysis. A dose-dependent inhibition of virus growth was observed on concomitant incubation of (2'-5')(A)n-poly(L-lysine) conjugates with vesicular stomatitis virus infected L1210 cell cultures. This was a result of the activation of the (2'-5')(A)n-dependent endoribonuclease (RNase L) by intracellularly delivered (2'-5')(A)n as in some IFN-treated virus-infected cells. Indeed, (2'-5')(A)n-poly(L-lysine) conjugates bind RNase L effectively as can be seen from their ability to compete with authentic (2'-5')(A)n in a cell-free radiobinding assay. Moreover, (2'-5')(A)n-poly(L-lysine) conjugates promote transient inhibition of protein synthesis and a characteristic cleavage pattern of ribosomal RNAs in intact cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of ribonuclease L by (2'-5')(A)4-poly(L-lysine) conjugates in intact cells. 301 97

Earlier studies demonstrated that synthetic peptides corresponding to the amino terminus of the vesicular stomatitis virus glycoprotein (G protein) have a pH-dependent hemolytic activity that is thought to be related to the fusion activity of G protein (R. Schlegel and M. Wade, J. Biol. Chem. 259: 4691-4694, 1984; R. Schlegel and M. Wade, J. Virol. 53: 319-323, 1985). A single amino acid change (lysine to glutamic acid at the amino terminus) abolishes the hemolytic activity of the peptide. Here we used oligonucleotide-directed mutagenesis to create a DNA encoding G protein with this same amino acid change at its amino terminus. The mutant protein encoded by this gene was expressed transiently in a monkey fibroblast cell line (COS) and was found to have a pH-dependent fusion activity indistinguishable from wild-type G protein. This result indicates that the hemolytic activity of the synthetic peptides was not related to the fusion activity of the G protein.
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PMID:Amino-terminal mutation of the vesicular stomatitis virus glycoprotein does not affect its fusion activity. 301 8

The conformations of synthetic peptides Lys-Phe-Phe-Phe-Ile-Ile-Gly-Leu-Ile-Ile-Gly-Leu-Phe-OCH3 and Lys(epsilon-palmitoyl)-Phe-Phe-Phe-Ile-Ile-Gly-Leu-Ile-Ile-Gly-Leu-Phe-O CH3, which constitute a part of the membrane-spanning region of the vesicular stomatitis virus G protein, have been studied by circular dichroism (CD) spectroscopy. Secondary structural features are observed for both peptides in trifluoroethanol, methanol, aqueous mixtures of trifluoroethanol and methanol and in a micellar environment. In trifluoroethanol, the CD spectra indicate the presence of a helical conformation, whereas in aqueous mixtures of organic solvents, both helical and beta-conformations are observed. While fatty acid acylation does not directly modulate peptide conformation, it promotes self-association of the acylated peptide and association with micelles. In a micellar environment, the acylated peptide adopts an alpha-helical conformation.
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PMID:Circular dichroism studies on a synthetic peptide corresponding to the membrane-spanning region of vesicular stomatitis virus G protein and its fatty acyl derivative. 302 85

Antisense oligonucleotides represent an interesting tool for selective inhibition of gene expression, but their efficient introduction within intact cells proved to be difficult to realize. As a step toward this goal, small (13- or 15-mer) synthetic oligodeoxyribonucleotides have been coupled at their 3' ends to epsilon-amino groups of lysine residues of poly(L-lysine) (Mr, 14,000). A 15-mer oligonucleotide-poly(L-lysine) conjugate complementary to the initiation region of vesicular stomatitis virus (VSV) N-protein mRNA specifically inhibits the synthesis of VSV proteins and exerts an antiviral activity against VSV when added in the cell culture medium at doses as low as 100 nM. Neither synthesis of cellular proteins nor multiplication of encephalomyocarditis virus was affected significantly by this oligonucleotide conjugate. The data suggest that oligonucleotide-poly(L-lysine) conjugates might become effective for studies on gene expression regulation and for antiviral chemotherapy.
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PMID:Specific antiviral activity of a poly(L-lysine)-conjugated oligodeoxyribonucleotide sequence complementary to vesicular stomatitis virus N protein mRNA initiation site. 302 96

Adult Beagles failed to respond to high concentrations of interferon (IF) when they were injected with a nuclease-resistant complex poly I:C with poly-L-lysine and carboxymethylcellulose (PICLC), by the IV or intrathecal route. An IV dose of 1 mg of PICLC/kg of body weight was lethal to 1 of 3 adult dogs, but induced IF in only 2 dogs. Smaller doses were less toxic, but also were less effective. The injection of a high dose of a known IF inducer (3 X 10(8) egg LD50 of Newcastle disease virus) also failed to induce IF in Beagles. Interferon could not be induced in vitro when primary cultures of neonatal dog lung or kidney were treated with cultures of neonatal dog lung or kidney were treated with PICLC. When these primary cell cultures were compared with the cell line Madin-Darby canine kidney in an IF assay, no difference in sensitivity to IF-induced protection from infection with vesicular stomatitis virus could be shown. This indicated that the sensitivity of the Madin-Darby cell line was not the only factor in determining the lack of IF response in dogs and indicates that the dogs are poor responders to IF induction.
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PMID:Minimal interferon induction in dogs, using a modified polyriboinosinic-polyribocytidylic acid complex. 616 81


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