UMLS:C0038362 - FACTA Search

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Query: UMLS:C0038362 (stomatitis)
8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine polyoma virus (MPyV) is a small DNA virus that induces tumors in multiple tissues of infected host. In this investigation, we show that cell lines derived from wild type virus-induced breast tumors are resistant to the growth inhibitory action of interferon beta (IFN-beta). Furthermore, replication of heterologous viruses such as vesicular stomatitis virus and encephalomyocarditis virus was not inhibited by IFN-beta in these cells. This effect was due to inhibition of IFN-stimulated gene expression by viral T antigen. Activation of IFN-stimulated gene factor 3 was inhibited in cells derived from a tumor induced by wild-type MPyV but not those from a mutant that lacks the pRB binding site of the large T antigen. Similarly IFN-gamma-inducible gene expression was also inhibited in cells transformed by wild-type virus. The levels of components of IFN-stimulated gene factor 3 and signal transducing Janus tyrosine kinases were comparable between the cells transformed by the wild-type and mutant viruses. The viral large T antigen bound to Janus tyrosine kinase 1 and inactivated signaling through IFN receptors. Thus, these studies identify a mechanism of viral resistance to IFN action.
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PMID:The polyoma virus T antigen interferes with interferon-inducible gene expression. 944 89

Oromucosal administration of murine interferon-alpha/beta (IFN-alpha/beta) or individual recombinant species of murine IFN-alpha, IFN-beta, or IFN-gamma or recombinant human IFN-alpha1-8, which is active in the mouse, exerted a marked antiviral activity in mice challenged systemically with a lethal dose of encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV), or varicella zoster virus (VZV). The effects observed were dose dependent and similar in magnitude to those observed following parenteral administration of the same dose of IFN. No antiviral activity was observed after oromucosal administration of murine IFN-alpha/beta in animals in which the IFN receptor had been inactivated by homologous recombination. In contrast to parenteral treatment, oromucosal IFN therapy was found to be ineffective when IFNs were administered before virus infection. Oromucosal administration of IFN-alpha also exerted a marked antitumor activity in mice injected i.v. with highly malignant Friend erythroleukemia cells or other transplantable tumors, such as L1210 leukemia, which has no known viral etiology, the EL4 tumor, or the highly metastatic B16 melanoma. These results show that high doses of IFN can be administered by the oromucosal route apparently without ill effect, raising the possibility that the oromucosal route will prove to be an effective means of administering high doses of IFN that are clinically effective but poorly tolerated.
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PMID:Oromucosal interferon therapy: marked antiviral and antitumor activity. 1009 Apr

Protein arginine N-methyltransferase (PRMT1) is one of the proteins that bind to the intracytoplasmatic domain of the IFNAR-1 chain of the type I interferon (IFN) receptor system. The attachment is specific and is not seen with PRMT2, another member of this protein family. Antisense PRMT1 cDNA constructs expressed under the early cytomegalovirus (CMV) promoter were transfected into HeLa cells, and stable transformants were selected. Antibodies to PRMT1 were used to identify clones with reduced PRMT1 expression. In such clones, IFN-beta inhibited three to five times less the replication of vesicular stomatitis virus (VSV) than in the original HeLa cells. The antiproliferative effect of IFN-beta was also reduced up to fivefold in the clones with low PRMT1 expression. No difference was seen when IFN-gamma was used alone to inhibit cell growth. The protein methylating enzyme, bound to IFNAR-1, appears to regulate positively the biologic activity of type I IFN.
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PMID:Involvement of receptor-bound protein methyltransferase PRMT1 in antiviral and antiproliferative effects of type I interferons. 1009 Apr 4

P56 is the most abundant protein induced by interferon (IFN) treatment of human cells. To facilitate studies on its induction pattern and cellular functions, we expressed recombinant P56 as a hexahistidine-tagged protein in Escherichia coli and purified it to apparent homogeneity using affinity chromatography. A polyclonal antibody raised against this recombinant protein was used to show that P56 is primarily a cytoplasmic protein. Cellular expression of P56 by transfection did not inhibit the replication of vesicular stomatitis virus and encephalomyocarditis virus. P56 synthesis was rapidly induced by IFN-beta, and the protein had a half-life of 6 h. IFN-gamma or poly(A)(+) could not induce the protein, but poly(I)-poly(C) or an 85-bp synthetic double-stranded RNA efficiently induced it. Similarly, infection of GRE cells, which are devoid of type I IFN genes, by vesicular stomatitis virus, encephalomyocarditis virus, or Sendai virus caused P56 induction. Surprisingly, Sendai virus could also induce P56 in the mutant cell line P2.1, which cannot respond to either IFN-alpha/beta or double-stranded RNA. Induction of P56 in the P2.1 cells and the parental U4C cells by virus infection was preceded by activation of IRF-3 as judged by its translocation to the nucleus from the cytoplasm.
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PMID:Induction of the human protein P56 by interferon, double-stranded RNA, or virus infection. 1066 16

We had previously reported that freshly harvested peritoneal macrophages (PM) are in a type I IFN-mediated antiviral state, which is lost during in vitro culture of PM, concomitantly with a progressive decline in the expression of IFN-beta. We report herein that in vitro culture of PM in the presence of IL-4 or IL-10 results in an enhanced decay of the IFN-beta-mediated antiviral state to vesicular stomatitis virus (VSV). Moreover, IL-4 and IL-10 inhibited the production of type I IFN induced by LPS or NDV infection, as assessed by IFN production and induction of IFN-mediated antiviral state. The accumulation and physiological turnover of IFN-beta mRNA was not affected by IL-4 or IL-10. Finally, neither IL-10 nor IL-4 exerted any inhibitory effect on the antiviral activity induced by exogenous type-I IFN. These results suggest that Th2 cytokines, such as IL-4 and IL-10, act as negative regulators of the type I IFN-mediated antiviral response in PM and may represent stop signals for the constitutive or induced type I IFN expression in PM.
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PMID:Inhibition of the constitutive and induced IFN-beta production by IL-4 and IL-10 in murine peritoneal macrophages. 1108 Apr 75

The induction of alpha/beta interferon (IFN-alpha/beta) genes constitutes one of the first responses of the cell to virus infection. The IFN-beta gene is constitutively repressed in uninfected cells and is transiently activated after virus infection. In this work we demonstrate that histone deacetylation regulates the silent state of the murine IFN-beta gene. Using chromatin immunoprecipitation (ChIP) assays, we show a direct in vivo correlation between the transcriptionally silent state and a state of hypoacetylation of histone H4 on the IFN-beta promoter region. Trichostatin A (TSA), a specific inhibitor of histone deacetylases, induced strong, constitutive derepression of the murine IFN-beta promoter stably integrated into a chromatin context, as well as the hyperacetylation of histone H4, without requiring de novo protein synthesis. We also show in this work that TSA treatment strongly enhances the endogenous IFN level and confers an antiviral state to murine fibroblastic L929 cells. Inhibition of histone deacetylation with TSA protected the cells against the lost of viability induced by vesicular stomatitis virus (VSV) and inhibited VSV multiplication. Using antibodies neutralizing IFN-alpha/beta, we show that the antiviral state induced by TSA is due to TSA-induced IFN production. The demonstration of the predominant role of histone deacetylation during the regulation of the constitutive repressed state of the IFN-beta promoter constitutes an interesting advance on the understanding of the negative regulation of this gene and opens up the possibility of new therapeutic perspectives.
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PMID:Inhibition of histone deacetylation induces constitutive derepression of the beta interferon promoter and confers antiviral activity. 1123 70

In the present study we show that malignant human papillomavirus (HPV)-positive cells lost their ability to synthesize endogenous beta interferon (IFN-beta) upon tumor necrosis factor alpha (TNF-alpha) treatment. IFN-beta transcription, however, was reinducible in nonmalignant HPV-positive cells, which was confirmed in functional protection assays against encephalomyocarditis virus or vesicular stomatitis virus infections. Addition of neutralizing antibodies against IFN-beta blocked the antiviral effect, excluding the possibility that other IFN types were involved. Conversely, both malignant and immortalized cells could be protected against viral cytolysis when either IFN-beta, IFN-alpha, or IFN-gamma was added exogenously. This indicates that only the cross talk between TNF-alpha and the IFN-beta pathways, and not IFN-alpha/beta and IFN-gamma signaling in general, is perturbed in cervical carcinoma cells. Notably, full virus protection was restricted exclusively to nonmalignant cells, indicating that the antiviral effect correlates with the growth-inhibitory and virus-suppressive properties of TNF-alpha. The IFN-regulatory factors IRF-1 and p48 (ISGF3gamma) emerged as key regulatory molecules in the differential IFN-beta response, since their transcription was either absent or only inefficiently enhanced in tumorigenic cells upon treatment with TNF-alpha. Inducibility of both genes, however, became reestablished in cervical carcinoma cells, which were complemented to nontumorigenicity after somatic cell hybridization. Complementation was paralleled by the entire reconstitution of cytokine-mediated IFN-beta expression and the ability of TNF-alpha to exert an antiviral state. In contrast, under conditions where tumor suppression was not accomplished upon somatic cell hybridization, neither expression of IRF-1, p48, and IFN-beta nor antiviral activity could be restored.
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PMID:Disturbance of tumor necrosis factor alpha-mediated beta interferon signaling in cervical carcinoma cells. 1173 93

Herpes simplex virus type 1 (HSV-1) is resistant to the antiviral effects of interferon (IFN)-alpha, -beta, or -gamma. The fact that ICP0(-) mutants replicate like wild-type virus in IFN-alpha/beta receptor knockout mice (Leib et al., 1999, J. Exp. Med. 189, 663) suggested that ICP0 may serve a direct role in the resistance of HSV-1 to IFN. To test this hypothesis, the effects of IFN-alpha, -beta, and -gamma were compared against wild-type HSV-1 and an ICP0(-) mutant virus, 7134. In Vero cells, 7134 was more sensitive to inhibition by low doses of type I IFN (-alpha/beta) or type II IFN (-gamma) than vesicular stomatitis virus, a well-studied IFN-sensitive virus. At a concentration of 100 U/ml, IFN-alpha, -beta, or -gamma reduced the efficiency of 7134 plaque formation by 120-, 560-, and 45-fold, respectively. In contrast, none of the IFNs reduced wild-type HSV-1 plaque formation by more than 3-fold. Even when Vero cells were infected with 10 pfu per cell, IFN-alpha and -beta inhibited 7134 replication by over 100-fold, but inhibition by IFN-gamma decreased to less than 10-fold. While IFN-beta efficiently inhibited 7134 replication in primary mouse kidney and SK-N-SH cells, IFN-gamma did not inhibit 7134 to a comparable extent in these cells. ICP0 provided in trans from an adenovirus vector allowed 7134 to replicate efficiently in Vero cells in the presence of IFN-alpha, -beta, or -gamma. While IFN-beta or -gamma efficiently repressed the ICP0 promoter-lacZ reporter gene in 7134 (i.e., approximately 60-fold reduction in beta-galactosidase activity), ICP0 provided in trans almost completely reversed IFN-mediated repression of the lacZ gene in 7134. The results suggest that the rate of ICP0 expression in infected cells in vivo may be critical in determining whether host IFNs repress the HSV-1 genome. This concept is discussed in light of its potential relevance to the establishment of latent HSV-1 infections.
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PMID:The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus to interferon-alpha/beta. 1188 49

The vesicular stomatitis virus (VSV) matrix (M) protein plays a major role in the virus-induced inhibition of host gene expression. It has been proposed that the inhibition of host gene expression by M protein is responsible for suppressing activation of host interferon gene expression. Most wild-type (wt) strains of VSV induce little if any interferon gene expression. Interferon-inducing mutants of VSV have been isolated previously, many of which contain mutations in their M proteins. However, it was not known whether these M protein mutations were responsible for the interferon-inducing phenotype of these viruses. Alternatively, mutations in other genes besides the M gene may enhance the ability of VSV to induce interferons. These hypotheses were tested by transfecting cells with mRNA expressing wt and mutant M proteins in the absence of other viral components and determining their ability to inhibit interferon gene expression. The M protein mutations were the M51R mutation originally found in the tsO82 and T1026R1 mutant viruses, the double substitution V221F and S226R found in the TP3 mutant virus, and the triple substitution E213A, V221F, and S226R found in the TP2 mutant virus. wt M proteins suppressed expression of luciferase from the simian virus 40 promoter and from the beta interferon (IFN-beta) promoter, while M proteins of interferon-inducing viruses were unable to inhibit luciferase expression from either promoter. The M genes of the interferon-inducing mutants of VSV were incorporated into the wt background of a recombinant VSV infectious cDNA clone. The resulting recombinant viruses were tested for their ability to activate interferon gene expression and for their ability to inhibit host RNA and protein synthesis. Each of the recombinant viruses containing M protein mutations induced expression of a luciferase reporter gene driven by the IFN-beta promoter and induced production of interferon bioactivity more effectively than viruses containing wt M proteins. Furthermore, the M protein mutant viruses were defective in their ability to inhibit both host RNA synthesis and host protein synthesis. These data support the idea that wt M protein suppresses interferon gene expression through the general inhibition of host RNA and protein synthesis.
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PMID:Ability of the matrix protein of vesicular stomatitis virus to suppress beta interferon gene expression is genetically correlated with the inhibition of host RNA and protein synthesis. 1266 71

The natural antiviral immunity of human lymphocytes, leukocytes from peripheral blood and whole-blood cultures was studied using the method of infection with two viruses belonging to different taxonomic groups, vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV). The kinetics of virus replication in the kinds of cultures and the dependence of culture infection on pre-infection incubation time were studied. When the cultures were infected immediately after preparation, most of them were found to be resistant to the viruses. However, when they were infected after several (1-5) days of incubation, VSV and EMCV multiplied in the cultures to high titers. The time of losing resistance was individually differentiated. The results indicate the presence of a non-specific antiviral immunity characteristic for individuals. The antiviral immunity of healthy donors was compared with that of people suffering from recurrent infections of the upper respiratory tract. This latter group expressed statistically significant lower innate immunity than healthy donors. However, there were no differences in interferon (IFN) and tumor necrosis factor (TNF) production between these groups. In order to examine the contribution of the endogenous IFNs and TNF-alpha in maintaining innate immunity, specific antibodies against IFN-alpha, IFN-beta, IFN-gamma and TNF-alpha were added to VSV-infected leukocytes resistant to infection. The antibodies reduced the antiviral resistance in 9 of 16 experiments. The results suggest that both endogenous interferons and TNF-alpha may participate in the constitution of innate immunity, though they are not the only mediators of it.
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PMID:Individual differentiation of innate antiviral immunity in humans; the role of endogenous interferons and tumor necrosis factor in the immunity of leukocytes. 1269 4

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