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)

Antiviral effects of prostaglandins of the A series (PGAs) on Sendai, vaccinia and vesicular stomatitis viruses have previously been reported and a relationship between the antiviral actions of PGAs and interferons has been suggested. We have investigated the antiviral activity of PGAs on encephalomyocarditis (EMC) virus. Using single-cycle assays of virus replication our results indicate that PGAs only inhibit when present in the culture medium after the cells are infected, and that they are most effective during incubation periods including from 3 to 5 h post-infection. Furthermore, viral RNA synthesis is blocked in infected cells treated with PGA and, as a result, viral antigens are greatly reduced in the cytoplasm of the cells 5 h post-infection. Since the antiviral effect of PGAs is unperturbed by actinomycin D, when cellular RNA synthesis is greatly reduced, it appears unlikely that induction of new cellular proteins is the reason for the antiviral activity of PGAs. In separate experiments we were unable to demonstrate directly the induction of interferon, or of the two dsRNA-dependent enzymes, 2',5'-oligoadenylate synthetase and protein kinase, which are greatly increased in interferon-treated cells. Thus, we conclude that the antiviral activity of PGAs is unrelated to the antiviral action of interferons and involves a unique mechanism independent of cellular protein synthesis.
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PMID:Antiviral activity of prostaglandin A on encephalomyocarditis virus-infected cells: a unique effect unrelated to interferon. 241 95

The C3H/HeJ mouse strain bears an autosomal gene defect, Lpsd, which results in a greatly diminished capacity to respond to endotoxin, the ubiquitous lipopolysaccharide derived from the cell walls of gram-negative bacteria. These mice also exhibit greater susceptibility to a variety of viral and bacterial infections than syngeneic, fully lipopolysaccharide-responsive (Lpsn) mouse strains and possess macrophages with defects in differentiation which are reversed by treatment with exogenous interferon (IFN). To test directly the hypothesis that C3H/HeJ macrophages are deficient in endogenous IFN levels, macrophages from C3H/HeJ (Lpsd) and C3H/OuJ (Lpsn) mice were compared for sensitivity to vesicular stomatitis virus. At a multiplicity of infection of 0.1, C3H/OuJ macrophages were completely refractory to infection, whereas C3H/HeJ macrophages were permissive for replication, and infection resulted in 100% cytopathic effect. These findings were confirmed with a second inbred Lpsn and Lpsd strain pair. Levels of 2',5'-oligoadenylate synthetase were significantly higher in Lpsn cells. C3H/HeJ macrophages, derived from bone marrow precursors under the influence of macrophage colony-stimulating factor, shown previously to induce IFN in macrophages, were as refractory as C3H/OuJ macrophages. Exposure of nonpermissive macrophages to anti-IFN-alpha/beta antibody prior to infection rendered cells permissive. Our findings suggest that endotoxin provides a primary stimulus for the maintenance of normal macrophage differentiation and innate resistance via the induction of endogenous IFN by macrophages.
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PMID:Macrophages from endotoxin-hyporesponsive (Lpsd) C3H/HeJ mice are permissive for vesicular stomatitis virus because of reduced levels of endogenous interferon: possible mechanism for natural resistance to virus infection. 243 68

The human rhabdomyosarcoma cell line RD-114 is partially responsive to interferons (IFNs). In these cells, alpha interferon (IFN-alpha) or gamma interferon (IFN-gamma) inhibits the replication of some viruses but not of others. Similarly, some of the IFN-inducible mRNAs are induced poorly, whereas others are induced well. Here we report the isolation of clonal derivatives of this line which display different spectra of responses to IFNs. Among the eight extensively characterized clonal lines, one, C10, did not respond to IFN-alpha or IFN-gamma at all. Retrovirus production by each of the seven other lines was inhibited by both IFN-alpha and IFN-gamma. Replication of vesicular stomatitis virus was inhibited strongly by IFN-alpha in clone B1 but not in others, whereas it was not appreciably affected by IFN-gamma in any clone. Replication of encephalomyocarditis virus was inhibited strongly by IFN-gamma in clones A1, A2, A3, B3, and B8 and by IFN-alpha in clone A2. Neither IFN inhibited the multiplication of these clones greatly, although their doubling times were slightly increased. Five mRNAs were induced by IFNs to varying degrees in the seven clones. mRNA 2A was most strongly induced by IFN-gamma in clone A3. mRNA 1-8 was strongly induced by IFN-alpha in clone A1 and by either IFN in clones A2 and A3. The highest concentrations of 2',5'-oligoadenylate synthetase mRNA, mRNA 561, and mRNA 6-16 were in IFN-alpha-treated clones A1 and A2. These results demonstrated the existence of clonal heterogeneity in IFN responses in a cell line and strengthened the view that IFN treatment of cells generates multiple signals leading to a variety of IFN-induced phenotypes.
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PMID:Clonal derivatives of the RD-114 cell line differ in their antiviral and gene-inducing responses to interferons. 244 Oct 75

Interferons, in addition to their antiviral activity, induce a multiplicity of effects on different cell types. Interferon (IFN)-gamma exerts a unique regulatory effect on cells of the mononuclear phagocyte lineage. To investigate whether the antiviral and antiproliferative effects of IFN-gamma in macrophages can be genetically dissociated, and whether IFN-alpha and IFN-gamma use the same cellular signals and/or effector mechanisms to achieve their biologic effects, we have derived a series of somatic cell genetic variants resistant to the antiproliferative and/or antiviral activities of IFN-gamma. Two different classes of variants were found: those resistant to the antiproliferative and antiviral effects of IFN-gamma against vesicular stomatitis virus (VSV) and those resistant to the antiproliferative effect, but protected against VSV and encephalomyocarditis virus (EMCV) lysis by IFN-gamma. In addition, a third class of mutants was obtained that was susceptible to the growth inhibitory activity, but resistant to the antiviral activity of IFN-gamma. Analysis of these mutants has provided several insights regarding the regulatory mechanisms of IFN-gamma and IFN-alpha on the murine macrophage cell lines. The antiproliferative activity of IFN-gamma on these cells, in contrast to that of IFN-alpha, is mediated by a cAMP-independent pathway. The antiproliferative and antiviral activities of IFN-gamma were genetically dissociated. Variants were obtained that are growth resistant but antivirally protected, or are growth inhibited but not antivirally protected against VSV or EMCV. The genetic analysis indicated that IFN-alpha and IFN-gamma regulate the induction of the dsRNA-dependent P1/eIF-2 alpha protein kinase and 2',5'-oligoadenylate synthetase enzymatic activities via different pathways. Finally, a unique macrophage mutant was obtained that was protected by IFN-gamma against infection by VSV, but not EMCV, suggesting that antiviral mechanisms involved in protection against these different types of RNA viruses must be distinct at some level.
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PMID:Regulation of macrophage growth and antiviral activity by interferon-gamma. 254 78

Infectious leukemia virus production by two chronically infected NIH/MOL lines was strongly inhibited by interferon treatment of the cells. The corresponding degree of inhibition in JLSV-11 cells was much lower. Multiplication of encephalomyocarditis virus in all three cell lines was barely affected by interferon treatment. Replication of vesicular stomatitis virus, on the other hand, was highly sensitive to interferon in the JLSV-11 line and in one NIH/MOL line but was practically insensitive in the other NIH/MOL line. Anticellular actions of interferon were more pronounced in the JLSV-11 line than in the others. In response to interferon treatment, 2',5'-oligoadenylate synthetase activity was induced to a high level in JLSV-11 cells and to lower levels in the NIH/MOL lines. We failed to detect any 2',5'-oligoadenylate-dependent endonuclease activity in extracts of these cells. Double-stranded RNA-dependent protein kinase activity was present in extracts of interferon-treated NIH/MOL cells, but it was barely detectable in extracts of interferon-treated JLSV-11 cells. The above studies demonstrated that interferon could differentially affect the replication of three different viruses in three different cell lines, including two seemingly identical NIH/MOL lines, and that certain tentative conclusions can be drawn regarding the roles of different interferon-inducible enzyme markers in the different antiviral actions of interferons.
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PMID:Differential antiviral effects of interferon in three murine cell lines. 618 40

An ex vivo antiviral assay was established which uses hepatocytes from mice given recombinant mouse interferon-beta (rmIFN-beta). Assay results were compared with results obtained with a 2',5'-oligoadenylate synthetase (2-5AS) assay. rmIFN-beta was intraperitoneally administered to C3H mice and the antiviral state of their liver parenchymal cells was evaluated in an in vitro cytopathic effect assay. In this assay, cells are infected with vesicular stomatitis virus (VSV) and surviving cells are determined colorimetrically. The antiviral state was measured as the resistance of hepatocytes to VSV infection with increasing doses of rmIFN-beta. The antiviral state correlated well with the dose-dependent increase in hepatic 2-5AS activity. This good correlation suggests that induction of 2-5AS mediates the antiviral action of interferon in liver tissue. This ex vivo assay could be a useful tool for estimating the ability of hepatocytes to resist hepatitis virus infection.
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PMID:An ex vivo assay for estimating the antiviral state of hepatocytes. 773 17

Interleukin-8 (IL-8), a proinflammatory chemokine, is induced by viruses and appears in circulation during viral infections. We found that IL-8 enhanced cytopathic effect induced by the positive strand RNA virus, encephalomyocarditis virus (EMCV), in the human WISH cell line. The enhancement was dependent on IL-8 dose and virus dose and was reversible by specific monoclonal antibodies to IL-8. The chemokine was also able to increase EMC viral RNA synthesis and infectious virus yield. This IL-8 enhancing action was not observed in the case of the negative strand RNA virus, vesicular stomatitis virus (VSV), in WISH cells. We examined the activity of constitutive 2',5'-oligoadenylate synthetase (OAS), a pathway that was implicated in protection from EMCV but not VSV. The IL-8 action in EMCV-infected cells, unlike VSV-infected cells, was associated with decreased OAS activity in a manner that was independent of OAS gene expression. Understanding mechanisms of cytokine enhancement of viral activity may lead to novel ways to control viral infections.
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PMID:Interleukin-8 selectively enhances cytopathic effect (CPE) induced by positive-strand RNA viruses in the human WISH cell line. 920 37

Hepatitis B, C, and D viruses can infect liver cells and in some individuals establish a chronic phase of infection. Presently, relatively little information is available on the antiviral mechanisms in liver cells. Because no good in vitro model infection systems for hepatitis viruses are available, we have used influenza A, Sendai, and vesicular stomatitis (VSV) viruses to characterize interferon (IFN) responses and IFN-induced antiviral mechanisms in human hepatoma cell lines. HepG2 or HuH7 cells did not show any detectable IFN-alpha/beta production in response to influenza A or Sendai virus infections. Treatment of cells with IFN-alpha resulted in upregulation of IFN-alpha-inducible Mx, 2',5'-oligoadenylate synthetase (OAS) and HLA class I gene expression but only with exceptionally high levels of IFN-alpha (>/=100 IU/ml). Accordingly, high pretreatment levels of IFN-alpha, 1000 IU/ml for influenza A and VSV and 100 IU/ml for Sendai virus, were required before any detectable antiviral activity against these viruses was seen. IFN-gamma had some antiviral effect against influenza A virus but appeared to be ineffective against VSV and Sendai virus. IFN-gamma upregulated HLA class I protein expression, whereas Mx or OAS expression levels were not increased. There was a modest upregulation of HLA class I expression during Sendai virus infection, whereas influenza A virus infection resulted, after an initial weak upregulation, in a clear decrease in HLA class I expression at late times of infection. The results suggest that hepatoma cells may have intrinsically poor ability to produce and respond to type I IFNs, which may contribute to their inability to efficiently resist viral infections.
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PMID:Impaired antiviral response in human hepatoma cells. 1054 9

Nine interferon-alpha subtypes, IFN-alpha1, IFN-alpha2, IFN-alpha5, IFN-alpha7, IFN-alpha8, IFN-alpha10, IFN-alpha14, IFN-alpha17, and IFN-alpha21, were separated from purified human lymphoblastoid IFN. We tested their inhibitory effects on cell growth and replication of Semliki Forest virus (SFV) and vesicular stomatitis virus (VSV) and their induction of 2',5'-oligoadenylate synthetase (2', 5'-OAS) in ACHN renal cell carcinoma cells. In terms of all three activities, the nine subtypes had similar relative activities, with IFN-alpha10 the most active and IFN-alpha1 the least. Their relative effects on cell growth were similar in two other human cell lines, SK-LU-1 lung cancer cells and KU-2 renal cell carcinoma cells, whereas cells of the Daudi Burkitt lymphoma line behaved quite differently, being highly sensitive to all the nine subtypes. The relative effects with ACHN cells correlated well with their relative binding affinities. However, each of the subtypes bound to both ACHN and Daudi cells to almost the same extent. This suggests that their profound inhibitory effects on the growth of Daudi cells are amplified at some stage in the signal transduction pathway or in the expression of genes that results from binding to the IFN-alpha receptor.
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PMID:Biologic and binding activities of IFN-alpha subtypes in ACHN human renal cell carcinoma cells and Daudi Burkitt's lymphoma cells. 1063 3

Control of viral replication by interferon (IFN) is thought to be principally mediated by the 2',5'-oligoadenylate synthetase (OAS)/RNAse L, double-stranded dependent protein kinase (PKR), and myxovirus resistance protein (Mx) pathways. In this study, we monitored the constitutive and IFN-induced antiviral activity in mouse embryo fibroblasts lines derived from mice with targeted disruption of either PKR or PKR/RNAse L genes. At high multiplicity of infection (moi = 10), the absence of PKR had no effect on replication of vesicular stomatitis virus (VSV) but moderately enhanced encephalomyocarditis virus (EMCV) growth and greatly increased replication of herpes simplex virus-1 (HSV-1). Replication of EMCV, HSV-1, and VSV was modestly higher in PKR-/- RNAse L-/- fibroblasts when compared with control cells. Although the antiviral action of IFN-alpha was unaffected by the absence of PKR, IFN action was significantly impaired in the double knockout cells but was dependent on the stage of the virus cycle. At early stages, it appeared that anti-EMCV and anti-HSV-1 action of IFN-alpha was significantly compromised, although weak residual antiviral activity was seen. The action of IFN-alpha against VSV was specifically compromised at a late stage of virus replication. The results showed that PKR is an important mediator in constitutive resistance against HSV-1 and that RNAse L is also necessary for the full antiviral activity of IFN against a variety of viruses. These results supported the existence of novel pathways aimed toward specific stages of the virus life cycle.
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PMID:Effect of deficiency of the double-stranded RNA-dependent protein kinase, PKR, on antiviral resistance in the presence or absence of ribonuclease L: HSV-1 replication is particularly sensitive to deficiency of the major IFN-mediated enzymes. 1092 8


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