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 monospecific inhibitory antibody directed to phospholipase C (phosphoinositidase C) blocked the antiviral effect of human interferons alpha and beta when tested on human quiescent fibroblasts challenged with the vesicular stomatitis virus. This action was due to specific inhibition of polyphosphoinositide hydrolysis because (a) the F(ab')2 fragment of the antibody molecule was also inhibitory; (b) excess antibodies directed to phospholipase A2 and to a phosphatidylcholine-preferring phospholipase C did not have any inhibitory effect, and (c) the combination of 12-O-tetradecanoyl-phorbol-acetate and calcium ionophore A23187 had an interferon-like antiviral effect which was not influenced by the inhibitory anti-phospholipase C antibodies. To avoid an interferon-like effect due to induction of interferon by second messengers, Vero cells, which lack interferon biosynthesis, were also used. Liposomes containing inositol 1,4,5-triphosphate and 1-oleoyl-2-acetyl-rac-glycerol protected Vero cells against the infection with the vesicular stomatitis virus. These results taken together show that phosphoinositide-derived second messengers are involved in triggering the antiviral effect of interferons alpha and beta.
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PMID:Cell-membrane phospholipase C is involved in inducing the antiviral effect of interferon. 250 82

Treatment of human amniotic cells (UAC) with human interferon-alpha (Hu-IFN alpha) or phorbol myristate acetate (PMA) resulted in translocation of protein kinase C (PK-C) activity from the cytosol fraction to that of the membranes. Analysis of 32P incorporation into phospholipid fractions and studies of alterations in fatty acid content for the major phospholipids of IFN-treated cells suggest that phospholipases C and A2 are activated by Hu-IFN alpha. Addition of neomycin (an inhibitor of phospholipase C), as well as mepacrine (an inhibitor of phospholipase A2) to IFN-treated cells inhibited the antiviral activity of Hu-IFN alpha in the vesicular stomatitis virus (VSV)-UAC system used. These observations indicate that (i) activation of PK-C and (ii) diacylglycerol formation, arachidonic acid and/or lysophosphatidylcholine release are important steps in the mechanism of action of IFN.
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PMID:Phospholipase C and phospholipase A2 are involved in the antiviral activity of human interferon-alpha. 254 50

The vesicular stomatitis virus glycoprotein forms noncovalently linked trimers in the endoplasmic reticulum before being transported to the Golgi apparatus. The experiments reported here were designed to determine if the extracellular domain of the glycoprotein contains structural information sufficient to direct trimer formation. To accomplish this, we generated a construct encoding G protein with the normal transmembrane and anchor sequences replaced with the sequence encoding 53 C-terminal amino acids from the Thy-1.1 glycoprotein. We show here that these sequences were able to specify glycolipid addition to the truncated G protein, probably after cleavage of 31 amino acids derived from Thy-1.1. The glycolipid-anchored G protein formed trimers and was expressed on the cell surface in a form that could be cleaved by phosphoinositol-specific phospholipase C. However, the rate of transport was reduced, compared with that of wild-type G protein. A second form of the G protein was generated by deletion of only the transmembrane and cytoplasmic domains. This mutant protein also formed trimers with relatively high efficiency and was secreted slowly from cells.
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PMID:Oligomerization of glycolipid-anchored and soluble forms of the vesicular stomatitis virus glycoprotein. 255 57

The antiviral effect of human interferons alpha and beta was inhibited in dose-dependent manner by submillimolar concentrations of neomycin, known to block phosphoinositide hydrolysis and therefore the diacylglycerol formation. On the contrary, the synthetic permeant diacylglycerols (1-oleoyl-2-acetyl-sn or rac-glycerol) were able to induce an interferon-like antiviral state when tested against the vesicular stomatitis virus and herpes simplex type I virus. Hidaka's compound H-8 (1.2 microM), expected to inhibit cAMP- and cGMP-dependent protein kinases, did not modify the antiviral effect of interferon. Our data suggest that the phosphoinositide pathway is involved in transducing the interferon antiviral signal, but, since the exogenous phospholipase C (0.1-1 U/ml) failed to induce an antiviral state, this pathway, although implicated, seems not the only one.
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PMID:Interferon-induced antiviral state is inhibited by neomycin and mimicked by diacylglycerols. 283 86

The chemical nature of the binding sites for vesicular stomatitis virus (VSV) was studied by measuring the ability of solubilized rat brain cell membranes (SRBM) to compete with cultured cells for viral binding. SRBM significantly reduced both binding and infectivity of VSV. After separation of protein and lipid components from membranes, VSV infection was unaffected by the protein fraction, whereas the lipid moiety, specifically phospholipids and glycolipids, showed a dose-dependent inhibitory effect. The essential role of phospholipid and sialic acid-containing glycolipid molecules as receptors for VSV was also suggested by the sensitivity of the inhibitory activity of SRBM and lipid components to phospholipase C and neuraminidase digestion.
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PMID:Characterization of rat brain cellular membrane components acting as receptors for vesicular stomatitis virus. Brief report. 283 50

Optical indicators of the cationic, cyanine and anionic oxonol classes were used to evaluate the plasma membrane potential of animal cells in suspension and in monolayer culture. The optical signals were calibrated by using diffusion potentials either of K+ (in the presence of valinomycin) or of H+ (in the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone; FCCP); both classes of dye gave similar values of plasma membrane potential, in the range -40 to -90 mV for different cell types. Addition of haemolytic Sendai virus or Staphylococcus aureus alpha-toxin depolarizes cells and causes them to leak monovalent cations; these effects are antagonized by extracellular Ca2+. Cells infected with vesicular stomatitis or Semliki Forest virus become depolarized during an infectious cycle; infection with other viruses was without affect on plasma membrane potential.
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PMID:Oxonol dyes as monitors of membrane potential: the effect of viruses and toxins on the plasma membrane potential of animal cells in monolayer culture and in suspension. 398 10

The cholesterol and phospholipid composition of the membrane of vesicular stomatitis (VS) virus was altered by growth in a sterol auxotroph Chinese hamster ovary (CHO MI) host cell and by infection of CHO MI and baby hamster kidney (BHK)-21 cells supplemented with fatty acids and dimethylethanolamine. VS virus released from infected CHO MI sterol auxotroph cells grown in delipidated serum had a 50% lower ratio of cholesterol to phospholipid and an 80% drop in infectivity measured by plaque formation on L-929 cells compared with VS virus released from infected CHO MI cells grown in fetal calf serum. When VS virus was harvested from infected BHK-21 cells fed the choline analogue dimethylethanolamine, 29% of the membrane phospholipids were phosphatidyldimethylethanolamine (PDME); 87% of the PDME was located in the external monolayer of the virus membrane as determined by phospholipase C hydrolysis. Exogenous fatty acids added to the medium of cells infected with VS virus comprised up to 30% of the fatty acyl chains of the viral glycerophospholipids. The presence of PDME or unusual fatty acyl chains in the viral membrane had no effect on viral infectivity. These data indicate that the lipid composition of the VS virus membrane is determined primarily by the lipids available in the host cell and that only cholesterol content affects the biological activity of the virus membrane.
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PMID:Alteration of the membrane lipid composition and infectivity of vesicular stomatitis virus by growth in a Chinese hamster ovary cell sterol mutant and in lipid-supplemented baby hamster kidney clone 21 cells. 624 9

The glycoprotein (G) of vesicular stomatitis virus (VSV) was radiolabelled, extracted and purified so that its potential interaction with host cell surfaces could be studied. When BHK-21 cells were incubated with the radiolabelled virus glycoprotein, the virus component rapidly attached to the cell surface. The attachment was shown to be temperature-dependent adn saturated at approx. 3 X 10(5) molecules/cell. The omission of Mg2+ or Ca2+ from the incubation medium had little effect on the glycoprotein binding. Treating the isolated G protein and intact virions with neuraminidase did not significantly decrease their binding to BHK-21 cells. Pre-incubating cells with trypsin did not decrease the attachment of VSV virions nor the binding of purified G protein. Treating cells with phospholipase A or phospholipase C suggested that the binding of the glycoprotein and the intact virion might have been dissimilar. Unlabelled glycoprotein competitively inhibited binding of the labelled molecules although the presence of intact virions did not inhibit attachment of the G protein. Likewise, saturating amounts of the glycoprotein did not decrease binding of VSV to BHK-21 cells. These observations suggested that either the isolated glycoprotein bound to cell surface components that were distinct from the virion receptor or that the manner of the purified glycoprotein attachment differed from the G protein still associated with the intact virion. Chemical crosslinking and diagonal two-dimensional gel electrophoresis were used to identify and to compare the cell surface components responsible for glycoprotein and virion attachment.
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PMID:Isolation of the glycoprotein of vesicular stomatitis virus and its binding to cell surfaces. 625 23

Recently we described a saturable, high-affinity binding site for vesicular stomatitis virus (VSV) on the surface of Vero cells that appears to mediate viral infectivity. To isolate this binding site, we have extracted Vero cells with the detergent, octyl-beta-D-glucopyranoside. The dialyzed detergent extract specifically inhibits the saturable, high-affinity binding of 35S-methionine-labeled VSV to Vero cells. The inhibitory activity is resistant to protease, neuraminidase and heating to 100 degrees C. It is soluble in chloroform-methanol and inactivated by phospholipase C, suggesting that it is a phospholipid. Of various purified lipids tested, only phosphatidylserine was capable of totally inhibiting the high-affinity binding of VSV. The half-maximal inhibitory concentration for phosphatidylserine was 1 microM. Phosphatidylserine also inhibited VSV plaque formation by 80%-90%; Herpes simplex virus plaque formation was unaffected. Centrifugation and electron microscopy studies have shown that phosphatidylserine-containing liposomes bind to VSV. The finding that phosphatidylserine directly binds to VSV and inhibits VSV attachment and infectivity suggests that plasma membrane phosphatidylserine could function as a binding site or portion of a binding site for VSV.
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PMID:Inhibition of VSV binding and infectivity by phosphatidylserine: is phosphatidylserine a VSV-binding site? 629 4

The surface potential of membranes of vesicular stomatitis virus and liposomes was determined by shift of ionization over a wide pH range of the membrane-inserted fluorophore, 4-heptadecyl-7-hydroxycoumarin. Incorporation into sonicated vesicles of negatively charged phosphatidylserine markedly increased the surface potential of uncharged phosphatidylcholine, but no significant effect on surface potential was produced by polar but uncharged glucocerebroside incorporated in phosphatidylcholine vesicles. The membrane of vesicular stomatitis virus was found to have a moderately high surface potential. Contributing to this viral membrane surface potential were glycoprotein spikes and phospholipid headgroups as determined by lowered charge after treatment of intact virions with thermolysin to remove glycoprotein or phospholipase C to remove phospholipid headgroups. The role of viral glycoprotein was confirmed by demonstrating increased surface charge of vesicles reconstituted with both viral glycoprotein and lipids compared with vesicles reconstituted with viral lipids alone. An unexpected finding was the large contribution to surface potential of cholesterol present in viral membrane. Increasing cholesterol concentration in virions by interaction with cholesterol-complexed serum lipoproteins resulted in a marked decrease in surface potential, whereas 75% depletion of virion cholesterol by interaction with sphingomyelin-complexed serum lipoproteins resulted in a significant increase in virion membrane surface potential. Although removal of glycoprotein spikes or depletion of cholesterol causes reduction in infectivity of vesicular stomatitis virus, no direct correlation could be found between alteration in surface charge and infectivity.
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PMID:Lipid and protein contributions to the membrane surface potential of vesicular stomatitis virus probed by a fluorescent pH indicator, 4-heptadecyl-7-hydroxycoumarin. 629 50


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