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

Human fibroblast interferon (Hu IFN beta) was directly introduced with glass micropipets into the cytoplasm of Hela cells. Such an injection of more than 10(4) molecules per cell failed to induce any antiviral state when challenged with vesicular stomatitis virus (VSV). These findings are discussed in relation to the possible role of internalization in the mechanism of antiviral action of interferon.
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PMID:Microinjected interferon does not promote an antiviral response in Hela cells. 630 39

Four hybrid human leukocyte interferon (IFN-alpha) genes have been constructed and expressed in Escherichia coli using molecular cloning methods. Plasmids containing genes encoding human interferons, IFN-alpha A, IFN-alpha D, IFN-alpha I and several hybrids of the different IFN-alpha genes (formed by in vitro recombination at common restriction endonuclease sites located within the DNA sequence encoding mature polypeptides) joined identically to an E. coli trp promoter gave rise to bacterial-produced interferons with distinctly different antiviral activities. The expression plasmid which directs the synthesis of IFN-alpha I was constructed using a gene isolated from a human genomic library in a manner similar to the previous expression of IFN-alpha A and IFN-alpha D cDNA clones. The use of a cell-free transcription-translation system has allowed the calculation of the specific activities of IFN-alpha made from isolated DNA fragments containing these hybrid IFN-alpha genes. These bacterially-derived interferons vary considerably in their ability to inhibit vesicular stomatitis virus (VSV) in different mammalian cells. The results show that the cloned hybrid interferons have unique antiviral activities when compared with the parent interferons, and they demonstrate that more active IFN-alpha s can be made using recombinant DNA techniques.
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PMID:Carboxyterminal region of hybrid leukocyte interferons affects antiviral specificity. 630 84

The kinetics of induction in human amnion U cells of the antiviral activity against vesicular stomatitis virus (VSV) produced by a single molecularly cloned subspecies of human leukocyte interferon (IFN-alpha A) were examined. IFN-alpha A-induced inhibition was found to be biphasic over a period of 24 h with the major extent of VSV inhibition occurring within the first 6 h of IFN treatment. The relationship of this major phase of inhibition to the early and late events of the VSV multiplication cycle was investigated. IFN-alpha A 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-treated cells, as compared to untreated cells. Progeny virions released from IFN-treated cells, although greatly reduced in number, were found to be equally as infectious as those released from untreated cells. Progeny virions from IFN-treated cells also had a normal complement of VSV proteins in the same ratios as were seen in virions from untreated cells; specifically, IFN treatment produced no reduction in the incorporation of G or M protein into assembled virions. These results suggest that conditions of IFN treatment sufficient to reduce the yield of infectious VSV progeny greater than 99% 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 leukocyte interferon. I. Effect on early and late stages of the viral multiplication cycle. 631 34

The effects of a single molecularly cloned subspecies of human leukocyte interferon (IFN-alpha A) on vesicular stomatitis virus (VSV) macromolecular synthesis in human amnion U cells were examined. IFN-alpha A was found to uniformly inhibit VSV protein synthesis to an extent sufficient to account for the overall inhibition of viral infectivity. IFN-alpha A treatment also prevented the shutoff of cellular protein synthesis observed in untreated, VSV-infected U cells. 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 IFN did not significantly inhibit the accumulation of VSV primary transcripts, although the in vivo translation of primary viral transcripts was greatly impaired as a function of IFN treatment. Thus, the major, and possibly only, effect of IFN-alpha A on VSV replication was translation inhibition. Analysis of RNA, separated 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-treated as compared to untreated cells. Likewise, in vitro protein synthesis did not reveal any major difference in the functional integrity of VSV mRNA isolated from IFN-treated as compared to untreated U cells. Viral mRNA isolated from either wild type or tsG41-infected U cells treated with IFN was translated only slightly less efficiently in vitro than viral mRNA from untreated cells. Thus, the principal cause of the IFN-induced inhibition of viral protein synthesis observed in vivo appears to be an alteration of a component of the translational machinery other than the mRNA template.
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PMID:Mechanism of interferon action: inhibition of vesicular stomatitis virus replication in human amnion U cells by cloned human leukocyte interferon. II. Effect on viral macromolecular synthesis. 631 35

The inhibition of virus replication and the induction of protein phosphorylation were examined in human amnion U and human fibroblast GM2767A cells treated with highly purified cloned human leukocyte and immune interferons synthesized in Escherichia coli. Both leukocyte interferon (IFN-alpha A) and immune interferon (IFN-gamma) possessed antiviral activity as measured by the single cycle yield reduction of vesicular stomatitis virus (VSV) in the human U and GM2767A cell lines. By contrast, only IFN-gamma and not IFN-alpha A inhibited the single cycle replication of reovirus in U and GM2767A cells. IFN-alpha A, but not IFN-gamma, efficiently induced the double-stranded RNA-dependent phosphorylation of the ribosome-associated protein P1 and the alpha subunit of protein synthesis initiation factor eIF-2 in U cells. However, neither IFN-alpha A nor IFN-gamma induced the phosphorylation of P1 and eIF-2 alpha in GM2767A cells. The antiviral activities of IFN-alpha A and IFN-gamma were synergistic for the inhibition of VSV but not for the inhibition of reovirus or the induction of protein phosphorylation. These results suggest that human leukocyte and immune interferons differentially regulate the expression of certain genes and induce mechanistically distinct antiviral states in human cells.
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PMID:Mechanism of interferon action: human leukocyte and immune interferons regulate the expression of different genes and induce different antiviral states in human amnion U cells. 631 41

Protein synthesis in interferon-treated HeLa cells infected by different animal RNA viruses has been studied. Synthesis of vesicular stomatitis virus (VSV) proteins was not detected in cells treated with concentrations of HuIFN-alpha (Ly) above 10 IU/ml. No specific inhibition of glycosylation of the G protein was observed. In addition, inhibition of host protein synthesis in IFN-treated cells occurred when high multiplicities of VSV were used, even though no viral protein synthesis was detected. For other viruses, such as Newcastle disease virus, Semliki Forest virus, encephalomyocarditis virus and poliovirus, treatment of cells with interferon also led to inhibition of viral protein synthesis. However, influenza virus and reovirus protein synthesis in interferon-treated cells stayed at control levels. The finding of viral translation in influenza virus and reovirus-infected cells treated with interferon suggests that, at least for these two systems, the antiviral state is not mediated by the bulk inhibition of viral protein synthesis through the dsRNA-activated protein kinase, or the 2'-5' oligo(A) system.
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PMID:Action of human lymphoblastoid interferon on HeLa cells infected with RNA-containing animal viruses. 631 80

The effects of a subsaturating, long treatment (24 h) dose of a highly purified cloned subspecies of human leukocyte interferon (IFN-alpha A) on vesicular stomatitis virus (VSV) primary macromolecular synthesis in tsG41-infected human amnion U cells were examined. IFN-alpha A, under these conditions, was found to inhibit primary VSV protein synthesis ten-fold while producing no detectable effect on the amount or integrity of primary viral message transcripts. There was no selective reduction by IFN-alpha A of the VSV G or M proteins.
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PMID:Mechanism of interferon action. Inhibition of vesicular stomatitis virus in human amnion U cells by cloned human leukocyte interferon. 632 81

The cell sensitivity of recombinant human alpha interferons (rIFN-alpha) of greater than 95% purity (A,D and the hybrid A/D) and crude nature (B and F) was studied in human (WISH, HeLa, AG1732), bovine (MDBK, BT), monkey (Vero), mouse (L), rabbit (RK-13), and hamster (BHK-21) cells. Based on an activity of 100% in WISH cells, the other cells responded to rIFN-alpha A as follows: AG1732 (90%), HeLa (94%), and MDBK and BT cells (170-190%). Rabbit, mouse, and hamster cells had a relative sensitivity of less than 1%. rIFN-alpha B and F were essentially equivalent to rIFN-alpha A in terms of cell sensitivity, but MDBK and BT cells were about 20 times more sensitive to rIFN-alpha D than were WISH cells and rIFN-alpha D was 1/5 to 1/10 as active on L cells as on WISH cells. The activity of the hybrid IFN A/D on bovine, mouse, and human cells was similar. The inhibitory dose50 (U/ml) of rIFN-alpha A, B, D, and F against virus infections in WISH cells were: vesicular stomatitis virus (1-4), rhinovirus types 1 and 42 (2-18), and herpes simplex virus (HSV) type 2 (45-70). Type 1 HSV, Semliki Forest (SFV) and encephalomyocarditis (EMC) viruses were tested against only rIFN-alpha A and D where SFV and EMC were the most sensitive to both IFNs (ID50-SFV, 0.2 U/ml, EMC, 1.2 U/ml) while 13 U/ml of rIFN-alpha A and D inhibited Type 1 HSV. The various rIFN-alpha s did not exhibit different antiviral spectra in vitro. When tested in mice rIFN-alpha A did not protect against infections with SFV, EMC, HSV, or influenza viruses. rIFN-alpha D and A/D protected mice infected with EMC, SFV, or HSV.
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PMID:Cell and virus sensitivity studies with recombinant human alpha interferons. 632 91

HeLa cells show a decrease of susceptibility to the killing by natural killer (NK) cells when treated with IFN-alpha, beta, or gamma. The concentrations at which preparations of IFN-alpha or beta induce the resistance to killing are those which also induce resistance of HeLa cells to infection by vesicular stomatitis virus (VSV). Stimulation of the killing activity of NK cells is also induced at that same range of concentrations of IFN-alpha and beta. In contrast with preparations of IFN-gamma, induction of the resistance to killing occurs at IFN concentrations which have only marginal stimulatory effect on the activity of NK cells and have no antiviral effect against VSV. IFN-gamma, produced with cloned IFN-gamma cDNA, is as effective as lymphocyte-produced IFN in inducing the resistance to natural killing. The potent effect of IFN-gamma on the target cells is, therefore, not due to the function of lymphokines which might contaminate lymphocyte-produced preparations of IFN-gamma, but a genuine property of the IFN itself.
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PMID:Interferon-induced resistance to the killing by NK cells: a preferential effect of IFN-gamma. 640 52

Several hybrid human interferons have now been constructed by recombinant DNA techniques. Two of these hybrid interferons, IFN-alpha AD(Bgl) and IFN-alpha AD(Pvu) differ by only three amino acids, but IFN-alpha AD(Bgl) was fifteen times more potent than IFN-alpha AD(Pvu) in antiviral activity towards infection of mouse L-929 cells by vesicular stomatitis virus. Only the hybrid with the greater antiviral activity in the mouse depressed cytochrome P-450, aminopyrine N-demethylase and benzo[a]pyrene hydroxylase in the liver. These experiments demonstrate that minor changes in amino acid structure not only have a major effect on the antiviral properties of interferon but also influence the ability of interferon to depress cytochrome P-450 in the liver.
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PMID:Relationship between the antiviral effects of interferons and their abilities to depress cytochrome P-450. 650 41


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