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 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

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

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

Cationic phthalocyanines with either aluminum or silicon as the central metal were evaluated for their ability to inactivate viruses in red blood cell concentrates (RBCC) photodynamically. In addition, the virucidal potential of a substituted anionic phthalocyanine, aluminum dibenzodisulfophthalocyanine hydroxide (A1N2SB2POH) was evaluated and compared with that of the much studied anionic aluminum tetrasulfophthalocyanine hydroxide (A1PcS4OH). Based on the rate of inactivation of the lipid-enveloped vesicular stomatitis virus (VSV), the virucidal potential of these phthalocyanines was: HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) = SiPc[OSi(CH3)2-(CH2)3N+(CH3)3I-]2 (Pc 6) > A1PcOSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I- (Pc 21) = A1N2SB2POH = A1PcS4 > HOSiPc[OSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I-]2 (Pc 14) > A1PcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 2). Phthalocyanine ligand 14 and Pc 21 are new phthalocyanines, made by quaternizing known amino analogues. Compared to VSV, the rate of inactivation of Sindbis virus (another model lipid-enveloped virus) was identical when treated in red blood cells (RBC) with Pc 5 and slightly higher when treated with Pc 6 and A1PcS4OH. Treatment of RBCC containing cell-free human immunodeficiency virus (HIV-1) with Pc 5 or A1PcS4OH required 15 min of irradiation to inactivate (> 5 log10 reduction) the virus. The extent of HIV-1 inactivation with A1N2SB2POH was 3.7 log10 after 60 min of red light exposure. The RBC integrity after photosensitization was measured by the ability of the cells to bind to plates coated with poly-L-lysine, (which reflects the retention of the RBC surface negative charges) and hemolysis of the cells over a 7 day storage period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New phthalocyanines for photodynamic virus inactivation in red blood cell concentrates. 793 15

Recently, the vesicular stomatitis virus matrix (M) protein has been shown to be capable of inhibition of host cell-directed transcription in the absence of other viral components (B. L. Black and D. S. Lyles, J. Virol. 66:4058-4064, 1992). M protein is a major structural protein that is known to play a critical role in virus assembly by binding the helical ribonucleoprotein core of the virus to the cytoplasmic surface of the cell plasma membrane during budding. In this study, two M protein mutants were tested to determine whether the inhibition of host transcription by M protein is an indirect effect of its function in virus assembly or whether it represents an independent function of M protein. The mutant M protein of the conditionally temperature-sensitive (ts) vesicular stomatitis virus mutant, tsO82, was found to be defective in its ability to inhibit host-directed gene expression, as shown by its inability to inhibit expression of a cotransfected target gene encoding chloramphenicol acetyltransferase. The ability of the tsO82 M protein to function in virus assembly was similar to that of wild-type M protein, as shown by its ability to complement the group III ts M protein mutant, tsO23. Another mutant, MN1, which lacks amino acids 4 to 21 of M protein demonstrated that the abilities of M protein to inhibit chloramphenicol acetyltransferase gene expression and to localize to the nucleus were unaffected by deletion of this lysine-rich amino-terminal region but that the ability to function in virus assembly was ablated. Thus, the two M protein mutants examined in this study exhibited complementary phenotypes: tsO82 M protein functioned in virus assembly but was defective in inhibition of host-directed gene expression, while MN1 M protein functioned in inhibiting gene expression but was unable to function in virus assembly. These data demonstrate that the role of M protein in inhibition of host transcription can be separated genetically from its role in virus assembly.
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PMID:The role of vesicular stomatitis virus matrix protein in inhibition of host-directed gene expression is genetically separable from its function in virus assembly. 839 15

A direct antiviral role of the interferon-induced human protein kinase p68 has been shown only against encephalomyocarditis virus (EMCV) and vaccinia virus (VV). To determine if p68 kinase (PKR) has a broad antiviral effect, we have used coinfections between VV recombinants expressing p68 kinase under regulation of the lac I operator/repressor elements of Escherichia coli and two RNA viruses, vesicular stomatitis virus (VSV) and poliovirus. In cells coinfected with VV recombinants and VSV, induction with isopropyl-B-D-thiogalactoside (IPTG) of wild-type p68 kinase or a mutant lacking the dsRNA binding domain resulted in inhibition of both VV and VSV protein synthesis. This inhibition is not observed in cells infected with a catalytically inactive point mutant lys-arg296 of p68 kinase. When cells are coinfected with VV recombinants and poliovirus, induction of active p68 kinase resulted in a decrease in VV proteins but not in poliovirus proteins or poliovirus yields. Immunoblot analysis revealed that p68 kinase was expressed during mixed infections. Our results demonstrate a differential effect of p68 kinase on the replication of VV, VSV, and poliovirus. We suggest that in a particular virus-cell system, the different sensitivity of a virus to p68 kinase is probably due to levels of active enzyme.
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PMID:Regulated expression of the interferon-induced protein kinase p68 (PKR) by vaccinia virus recombinants inhibits the replication of vesicular stomatitis virus but not that of poliovirus. 897 11

The existence of specific rabies virus (RV) glycoprotein (G) binding sites on the surfaces of neuroblastoma cells is demonstrated. Spodoptera frugiperda (Sf21) cells expressing G of the RV strain CVS (Gcvs-Sf21 cells) bind specifically to neuroblastoma cells of different species but not to any other cell type (fibroblast, myoblast, epithelial, or glioma). Attachment to mouse neuroblastoma NG108-15 cells is abolished by previous treatment of Gcvs-Sf2 cells with anti-G antibody. Substitutions for lysine at position 330 and for arginine at position 333 in RV G greatly reduce interaction between Gcvs-Sf21 cells and NG108-15 cells. These data are consistent with in vivo results: an avirulent RV mutant bearing the same double mutation is not able to infect sensory neurons or motoneurons (P. Coulon, J.-P. Ternaux, A. Flamand, and C. Tuffereau, J. Virol. 72:273-278, 1998) after intramuscular inoculation into a mouse. Furthermore, infection of NG108-15 cells by RV but not by vesicular stomatitis virus leads to a reduction of the number of binding sites at the neuronal-cell surface. Our data strongly suggest that these specific attachment sites on neuroblastoma cells represent a neuronal receptor(s) used by RV to infect certain types of neurons in vivo.
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PMID:Neuronal cell surface molecules mediate specific binding to rabies virus glycoprotein expressed by a recombinant baculovirus on the surfaces of lepidopteran cells. 944 3

The IFN-tau are type I IFN expressed by the early trophoblast of cattle and sheep but have activity on human cells and have been predicted to have potential therapeutic value. We have compared a series of mutant bovine and ovine IFN-tau with regard to their ability to inhibit the proliferation of Daudi cells and to evoke an antiviral (AV) response in WISH cells. Whereas Daudi cell growth was inhibited by Bo-IFN-tau1 in the 1 nM range, WISH cells were much less responsive, requiring exposure to 150 nM for protection against vesicular stomatitis virus. Replacement of lysines at positions 34, 107, 121, and 132 in Bo-IFN-tau, which are in regions predicted to interact with the type I receptor, led to modest but significant alterations in antiproliferative (AP) and AV activities. Replacement of the lysine residues at 160 and 164 had marked effects on biopotency, with K160 being particularly important. The different IFN-tau were able to activate the transcription factors ISGF3 and AAF (GAF) in Daudi cells at concentrations that correlated reasonably well with their AP potencies. Stat activation occurred in WISH cells in response to approximately 2 nM Bo-IFN-tau1, but ISGF3 formation could not be demonstrated even at the 100-fold higher IFN-tau concentrations that gave viral protection. Pretreatment of WISH cells with Hu-IFN-gamma allowed ISGF3 formation to be observed in response to subsequent treatment with Bo-IFN-tau1 or type I human IFN but did not increase the AV responsiveness of the cells. No evidence was found that IFN-tau elicit uniquely different responses on human cells than type I Hu-IFN, except they are much less potent. The data emphasize the importance of a region near the carboxyl terminus for the functional activity of type I IFN, and that although ISFG3 formation may be necessary, its mere presence is not sufficient to provide an antiviral response.
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PMID:The antiproliferative and antiviral activities of IFN-tau variants in human cells. 945 65


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