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)

IFN-gamma is a secreted polypeptide product of stimulated T lymphocytes with immunomodulatory properties as well as antiviral activity. We have investigated the effects of IFN-gamma treatment on a neutralizing antibody response to vesicular stomatitis virus (VSV) when administered in conjunction with immunization using purified envelope glycoprotein "G" of VSV. Administration of rIFN-gamma to mice or cattle at the time of primary immunization with VSV G glycoprotein enhanced the magnitude of a secondary virus-neutralizing antibody response after a booster administration of the same Ag without IFN-gamma treatment. Enhancement was statistically significant and occurred at relatively low doses of IFN-gamma in the absence of any additional adjuvants. Furthermore, cattle treated with IFN-gamma at the time of a single primary immunization were more resistant to VSV challenge than those immunized without IFN-gamma treatment. IFN-gamma treatment in conjunction with a single primary immunization may therefore provide a practical means of enhancing protection from a viral challenge without the use of inflammatory adjuvants or booster immunizations.
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PMID:Enhancement of a secondary antibody response to vesicular stomatitis virus "G" protein by IFN-gamma treatment at primary immunization. 283 43

The effects of interferon (IFN)-gamma or IFN-alpha/beta on virus yield, (2'-5')oligo(A) synthetase activation, H-2 antigen expression and proliferation of T lymphocytes have been investigated. Under the culture conditions used, vesicular stomatitis virus or Semliki Forest virus replication in T cells was not impaired by the addition of IFN-gamma, whereas it was completely inhibited by the addition of IFN-alpha/beta. In contrast, B cell lines, macrophage-transformed cell lines and fibroblasts were fully protected by both IFN-gamma as well as IFN-alpha/beta following virus infection. The lack of sensitivity of T lymphocytes to the antiviral effects of IFN-gamma was not due to absence of specific membrane receptors, since in saturation binding experiments with 125I-labeled murine IFN-gamma most T cell lines displayed a number of binding sites and a degree of affinity comparable to those found on B cells, which are fully sensitive to IFN-gamma antiviral activity. Analysis of IFN-induced dsRNA-dependent (2'-5')oligo(A) synthetase activity, one of the biochemical markers for cellular responses to IFN, showed that it was not induced in T lymphocytes after IFN-gamma treatment, whereas IFN-alpha/beta induced high levels. Both IFN-gamma and IFN-alpha/beta enhanced H-2 antigen expression on T cells as well as on cells of different histological type. Moreover, when IFN-gamma was tested for its antiproliferative activity on T cells, it was found to consistently potentiate the response of these cells to mitogens or growth factors, rather than inhibit their proliferation. Taken as a whole these results suggest that on T lymphocytes IFN-gamma should not be regarded as an antiviral agent, but rather as a modulator of T cell growth and functional differentiation, transducing intracellular signals dissimilar to those observed with target cells of different origin.
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PMID:Interferon-gamma is not an antiviral, but a growth-promoting factor for T lymphocytes. 283 46

The molecular basis of the inhibition of vesicular stomatitis virus (VSV) replication by pure recombinant gamma-interferon (IFN-gamma) in human amnion U cells was examined. A saturating concentration of IFN-gamma induced, at maximum, about a two log10 reduction in infectious VSV yield. The kinetics of induction of the antiviral activity by IFN-gamma were first order over the period of about 6-18 h, following a lag of about 3 h, after treatment with a saturating concentration of IFN-gamma. The relationship of the inhibition in VSV infectivity to the early and late events of the VSV multiplication cycle was investigated. IFN-gamma treatment had no detectable effect on the adsorption and penetration of VSV virions or on their uncoating to yield viral nucleocapsids. The polypeptides of adsorbed or uncoated VSV particles were neither preferentially degraded nor detectably altered in IFN-gamma-treated U cells, as compared to untreated U cells. Progeny virions isolated from IFN-gamma-treated U cells, although greatly reduced in number, were found to be equally as infectious as those isolated from untreated U cells. Progeny virions from IFN-gamma-treated cells also possessed the same composition of viral proteins as was observed for virions from untreated cells. These results suggest that conditions of IFN-gamma treatment sufficient to reduce the yield of infectious VSV progeny 100-fold do not detectably affect either the early or the late stages of the VSV multiplication cycle.
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PMID:Mechanism of interferon action: inhibition of vesicular stomatitis virus replication in human amnion U cells by cloned human gamma-interferon. I. Effect on early and late stages of the viral multiplication cycle. 298 1

The effects of recombinant human gamma-interferon (IFN-gamma) on vesicular stomatitis virus (VSV) macromolecular synthesis in human amnion U cells were examined. Saturating concentrations of IFN-gamma caused only a 3 to 5-fold reduction of viral protein synthesis in wild-type VSV-infected cells, an extent insufficient to account for the 100-fold inhibition of viral infectivity. By use of the VSV mutant tsG41, which is competent in RNA transcription but defective in RNA replication at 40 degrees C, it was shown that the apparent IFN-induced inhibition of viral protein synthesis was likely due to a reduction in the synthesis of primary transcripts in IFN-gamma-treated U cells. Dot blot hybridization analysis revealed that saturating concentrations of IFN-gamma reduced both primary (measured with mutant tsG41-infected U cells) and total (measured with wild-type-infected U cells) viral RNA synthesis by about 4-fold, an extent of inhibition comparable to the observed reduction in viral protein synthesis. Analysis of RNA, fractionated by agarose gel electrophoresis after denaturation with glyoxal, with cDNA probes to individual VSV mRNAs did not reveal any detectable difference in the structural integrity of VSV mRNA isolated from IFN-gamma treated as compared to untreated U cells. These results suggest that IFN-gamma treatment causes a small reduction in the efficiency of transcript formation catalyzed by input parental virions. However, the results also indicate that the principal cause of the IFN-gamma-induced inhibition of VSV replication in U cells is the alteration of a step in replication other than viral macromolecular synthesis. This implies that the molecular mechanism of viral inhibition by IFN-gamma is fundamentally different from that of IFN-alpha in human amnion U cells.
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PMID:Mechanism of interferon action: inhibition of vesicular stomatitis virus replication in human amnion U cells by cloned human gamma-interferon. II. Effect on viral macromolecular synthesis. 298 2

The cytotoxic effect of lymphotoxin (LT) and its modulation by interferon (IFN) was quantitatively assessed in uninfected and vesicular stomatitis virus (VSV)-infected cultured cells. Preparations of human LT, which were depleted of IFN, had a significant cytotoxic effect on VSV-infected HeLa, SV-80, WISH, and Vero cells. IFN, most notably IFN-gamma, further potentiated destruction of the infected cells by these LT preparations, when applied on the cells at sub-antiviral IFN concentrations. In contrast, no cytotoxic effect could be observed in any of the examined cells, when applying LT, IFN, or their combination, in the absence of viral infection. Infected cells in which VSV replication was suppressed by treatment with antiviral concentrations of IFN also resisted destruction by LT. These findings indicate that LT cytotoxicity can be selectively directed against virus-infected cells and that IFN can augment this cell-killing mechanism when failing to exert an antiviral effect.
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PMID:Increase of vulnerability to lymphotoxin in cells infected by vesicular stomatitis virus and its further augmentation by interferon. 298 52

The clinical value of interferon (IFN) level determinations has been demonstrated, but a practical assay procedure for routine use in the diagnostic laboratory has not been available. The authors examined the susceptibility of five cell lines (WISH, HEp-2, Vero, A549, and WI-26VA4) to vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV), and compared the response of these cells to the inhibitory activity of IFN-alpha and IFN-gamma for the respective viral cytopathic effect (CPE). The WISH-EMCV system was the most sensitive for IFN-alpha, and was approximately as sensitive as the HEp-2-VSV system for IFN-gamma. WISH cells were found to be significantly more sensitive for both IFN-alpha and IFN-gamma when EMCV, instead of VSV, was used (P less than 0.001). Therefore, the latter system served as the basis for developing a CPE dye-uptake procedure that was found to be considerably more rapid but slightly less sensitive than the conventional technic. However, both procedures were equally reproducible and should be suitable for automation.
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PMID:A practical cytopathic effect/dye-uptake interferon assay for routine use in the clinical laboratory. 298 28

Upon ConA stimulation, peripheral blood mononuclear leukocytes from psoriatic patients show an impaired IFN-gamma production. Normal IFN-gamma values were obtained, however, with PHA or PWM as inducers. Moreover, psoriatic cells responded well to vesicular stomatitis virus as inducer of IFN-alpha. Thus, the defect is not an all-out inability of all lymphocytes to produce IFN, but rather a failure to respond to weak mitogenic stimuli. Possible mechanisms are discussed.
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PMID:Differences in interferon-gamma response of psoriatic lymphocytes to stimulation with various mitogens. 302 30

RD-114 is a cell line which is partially responsive to interferon (IFN). Although both IFN-alpha and IFN gamma inhibit production of the resident retrovirus, they do not inhibit replication of other viruses, such as vesicular stomatitis virus and encephalomyocarditis virus, in these cells. In the studies reported here, we studied the characteristics of induction of seven IFN-inducible mRNAs in RD-114 cells. We observed that mRNAs 561, 6-16, 1-8, 2A, and 6-26 have similar induction characteristics in RD-114 cells and in HeLa cells, a fully responsive line. mRNA 2'-5'-oligo-adenylate synthetase (2-5(A) synthetase), however, was induced more efficiently by IFN-alpha in HeLa cells than in RD-114 cells. The same was true for the induction of metallothionein II mRNA by IFN-gamma. However, the latter mRNA was induced equally strongly in both lines when ZnCl2 was used as the inducer, suggesting that the gene is not defective in RD-114 cells. Although IFN-alpha induced 2-5(A) synthetase mRNA poorly and IFN-gamma did not induce it at all in these cells, a mixture of IFN-alpha and IFN-gamma induced this mRNA quite effectively, to a level of induction comparable to that in HeLa cells. Only 1 U of IFN-gamma per ml was sufficient to elicit this synergism, and the data suggested that an IFN-gamma-inducible protein was needed for this process. Induction of mRNA 561 by IFN-alpha in RD-114 cells, unlike that in HeLa cells, did not need ongoing protein synthesis. Once induced, this mRNA turned over rapidly in both cell lines, and this turnover could be slowed down by inhibiting protein synthesis in either cell line. IFN-induced mRNAs, such as 561 and 1-8, were polysome associated in IFN-treated RD-114 cells, suggesting that they were actively translated. Therefore, it is unlikely that the products of these IFN-inducible genes, by themselves, mediate the inhibition of replication of those viruses which are insensitive to IFN action in RD-114 cells.
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PMID:Expression of interferon-inducible genes in RD-114 cells. 310 49

A human T-lymphoblastoid cell line, TCL-Fuj, produces large amounts of interferon (IFN)-gamma constitutively. A variant cell line, 2M, was derived from it. Both cell lines express similar surface antigen markers, but differ in surface morphology. Compared with the parent TCL-Fuj cell line, 2M produced less IFN-gamma constitutively but more in response to IFN inducers. The IFNs produced constitutively and on stimulation with inducers were analyzed by SDS-polyacrylamide gel electrophoresis. In TCL-Fuj cells, the constitutive and induced IFNs consisted of the same molecular species (22K and 39K). In 2M cells, smaller IFNs were produced constitutively (18K and 32K) and induction resulted in a marked increase of 22K molecules. These two cell lines also differed in sensitivity to the antiviral activity of IFN. Other T-lymphoblastoid cell lines, HPB-ALL and TCL-Fuj 4 cells, which did not produce IFN-gamma were permissive for vesicular stomatitis virus (VSV) replication; its growth was markedly suppressed by IFN-gamma and -alpha. TCL-Fuj cells were also permissive for VSV, but were not susceptible to the antiviral effect of the IFNs. In contrast, in 2M cells the multiplication of VSV was restricted; the viral yield was further reduced by the IFNs and increased by treatment with anti-human IFN-gamma serum. Several clonal cell lines derived from TCL-Fuj and 2M cells had characteristics similar to the respective parent cell lines. The growth of both cell lines was not affected by IFN-gamma or by -alpha. The separation of antiviral and anti-proliferative susceptibilities was peculiar to 2M cells unlike other cell lines.
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PMID:Human T-lymphoblastoid cell lines with high and low abilities to produce interferon-gamma constitutively and their susceptibilities to interferon. 311 50

Variant sublines of Friend erythroleukemia cells (FLC) that do not respond to alpha/beta-interferon (IFN-alpha/beta) by developing an antiviral state but respond partially to IFN-gamma with an induced antiviral state, lack the ability to induce the 2',5'-oligoadenylate (2-5A) synthetase pathway. Exposure of wild-type and variant cells to exogenous 2-5A oligomers made permeable with lysolecithin resulted in 50-70% inhibition of protein synthesis. Further, the replication of vesicular stomatitis virus in IFN-resistant 2-5A synthetase-deficient FLC exposed to 2-5A trimer was inhibited to the same extent as in wild-type cells. Last, a significant cleavage of ribosomal RNA was observed in samples of total RNAs extracted from variant and wild-type permeabilized FLC, but only if they were exposed to 2-5A. These data are compatible with the conclusion that (i) the activation of the 2-5A-dependent endoribonuclease is not impaired in the variant cells, and (ii) the uninducibility of 2-5A synthetase can be bypassed by exogenously introducing its products, which leads to the establishment of a bona fide antiviral state.
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PMID:2',5'-Oligoadenylate synthetase-uninducible alpha/beta-interferon-resistant Friend cells develop an antiviral state when permeabilized with lysolecithin and treated with 2',5'-oligoadenylate oligomers. 346 65


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