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Long-Term Effect of Interferon on Keratinocytes That Maintain Human Papillomavirus Type 31

Chang, Yijan E.; Pena, Loren; Sen, Ganes C.; Park, Jung K.; Laimins, Laimonis A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2002 Português
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The long-term effects of interferon treatment on cell lines that maintain human papillomavirus type 31 (HPV-31) episomes have been examined. High doses and prolonged interferon treatment resulted in growth arrest of HPV-positive cells, with a high percentage of cells undergoing apoptosis. These effects were not seen with interferon treatment of either normal human keratinocytes or cells derived from HPV-negative squamous carcinomas, which exhibited only slight decreases in their rates of growth. Within 2 weeks of the initiation of treatment, a population of HPV-31-positive cells that were resistant to interferon appeared consistently and reproducibly. The resistant cells had growth and morphological characteristics similar to those of untreated cells. Long-term interferon treatment of HPV-positive cells also resulted in a reduction in HPV episome levels but did not significantly decrease the number of integrated copies of HPV. Cells that maintained HPV genomes lacking E5 were sensitive to interferon, while cells expressing only the E6/E7 genes were resistant. In contrast, cells that expressed E2 from a tetracycline-inducible promoter were found to be significantly more sensitive to interferon treatment than parental cells. This suggests that at least a portion of the sensitivity to interferon could be mediated through the E2 protein. These studies indicate that cells maintaining HPV episomes are highly sensitive to interferon treatment but that resistant populations arise quickly.

Effect of interferon on the replication of mink cell focus-inducing virus in murine cells: synthesis, processing, assembly, and release of viral proteins.

Bilello, J A; Wivel, N A; Pitha, P M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1982 Português
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Treatment of mink cell focus-inducing (MCF) virus (isolate AK-13) producing SC-1 cells with mouse fibroblast interferon (150 to 600 U/ml) led to a 100-fold decrease in the release of infectious virus, whereas there was a 2.5- to 10-fold decrease in various parameters of virus particle release. Analysis of labeled virion proteins indicated that a temporal change in virion protein composition occurred after interferon treatment. After a 24-h exposure of chronically infected cells to interferon, the virions produced contained a 85,000-dalton glycoprotein (apparently of nonviral origin) which was in excess of the virus envelope glycoprotein gp70. Particles produced from cells treated with interferon for 32 to 48 h were nearly devoid of gp70 and contained substantially lower quantities of p30. Intracellular processing of viral precursor polyproteins to the mature virion structural proteins was not altered in the presence of interferon. However, an accumulation of the viral p30 and p12E proteins was observed in interferon-treated cells, consistent with an increase in cell-associated virions. Immunoprecipitation analysis of the tissue culture fluids from [35S]methionine-labeled control and interferon-treated cells revealed marked decrease in p30 and p15E/p12E released after interferon treatment. In contrast...

Mouse fibroblast interferon modifies Salmonella typhimurium infection in infant mice.

Bukholm, G; Berdal, B P; Haug, C; Degré, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1984 Português
Relevância na Pesquisa
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The effect of mouse fibroblast interferon on Salmonella typhimurium infection in infant mice was examined. The lethality to mice that had been given S. typhimurium intragastrically was significantly reduced in a dose-dependent manner when the mice were pretreated with fibroblast interferon. Lower doses of interferon delayed the development of disease. Interferon neutralized with anti-interferon globulin did not influence the lethality of S. typhimurium to mice. In mice treated with interferon there was also a reduced invasiveness of S. typhimurium in intestinal epithelial cells in vivo. It was further demonstrated in an in vitro system that interferon pretreatment of mouse L-929 cells inhibited the invasiveness of the bacteria in a dose-dependent manner. The in vitro inhibition was neutralized with anti-interferon globulin. The results indicate that interferon inhibits Salmonella bacteria from invading cells and establishing an intracellular state of infection. This may represent an important factor in the pathogenesis of disease.

Interferon Production by Inactivated Newcastle Disease Virus in Cell Cultures and in Mice

Youngner, Julius S.; Scott, Anne W.; Hallum, Jules V.; Stinebring, Warren R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1966 Português
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Youngner, Julius S. (University of Pittsburgh, Pittsburgh, Pa.), Anne W. Scott, Jules V. Hallum, and Warren R. Stinebring. Interferon production by inactivated Newcastle disease virus in cell cultures and in mice. J. Bacteriol. 92:862–868. 1966.—A comparison was made of the effects of ultraviolet (UV) irradiation or heating at 56 C on the interferon-stimulating capacity of Newcastle disease virus in primary chick embryo fibroblast (CE) cultures, in L-cell cultures, and in the intact mouse. The data obtained indicated the critical importance of the host cell system used for interferon production. Virus inactivated by UV irradiation, as well as infective virus, was an effective stimulus of interferon production in L cells and in mice, and this property persisted on continued irradiation. In contrast, in CE cell cultures, infective virus produced no interferon, whereas UV-irradiated virus produced maximal interferon titers when all infectivity was destroyed; continued irradiation resulted in a rapid loss of the interferon-stimulating capacity of the virus. Virus inactivated at 56 C did not produce interferon in CE or L-cell cultures. In the intact mouse, on the other hand, heat-inactivated virus was capable of stimulating the release of significant levels of circulating interferon.

INTERACTION OF AN INTERFERON WITH L CELLS

Lockart, Royce Z.; Horn, Barbara
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1963 Português
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Lockart, Royce Z., Jr. (The University of Texas, Austin) and Barbara Horn. Interaction of an interferon with L cells. J. Bacteriol. 85:996–1002. 1963.—Data were presented on the effect of time of exposure and concentration of an interferon in provoking viral inhibition in L cells. Populations of L cells which made reduced amounts of Western equine encephalomyelitis virus as a result of treatment with interferon did so at reduced rates proportional to the concentration of interferon used. Virus yields were maximal, however, 25 hr after challenge regardless of the amount of virus produced. Such populations of cells contained a proportion of cells no longer able to produce infective virus, while the average maximal yield of the remainder of the cell population was reduced. It was suggested that only cells which made new virus underwent cytopathic effects. The rate of viral inhibition in monolayers of L cells was dependent on the concentration of interferon added, but inhibition was nearly maximal at 8 hr, regardless of the interferon concentration. Viral inhibition was shown to persist in multiplying cells, but it gradually diminished. The amount of inhibition after either one or two cell divisions was greater in those cultures treated with greater amounts of interferon. Viral inhibition could be passed through cell division with no loss when cells were incubated with a sufficient concentration of interferon. A model of interferon action based on the preceding data was presented.

Gamma interferon induces rapid and coordinate activation of mitogen-activated protein kinase (extracellular signal-regulated kinase) and calcium-independent protein kinase C in human monocytes.

Liu, M K; Brownsey, R W; Reiner, N E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1994 Português
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Gamma interferon plays an important role in regulating the functional properties of mononuclear phagocytes. In the present study, the role of activated protein kinases in the mechanism of action of gamma interferon cell signaling in human peripheral blood monocytes was investigated. Analysis in vitro of 100,000 x g cytosolic fractions from untreated and interferon-treated cells showed that agonist treatment resulted in time- and concentration-dependent increases in phosphotransferase activity when myelin basic protein (MBP) was used as the substrate. Anion-exchange chromatography of high-speed supernatants prepared from detergent extracts of interferon-treated cells revealed two discrete peaks of MBP phosphotransferase activity. Immunoblotting of fractions from these peaks with antiphosphotyrosine antibodies and with antibodies that specifically recognize the family of mitogen-activated protein (MAP) kinases detected a MAP kinase with a subunit M(r) of 42,000 in the earliest-eluting peak (peak 1). Phosphorylation of the 42,000-M(r) protein on tyrosine was observed only after treatment of cells with interferon. The contribution of MAP kinase to the interferon-stimulated activity in peak 1 was confirmed by quantitative immunoprecipitation with anti-MAP kinase and antiphosphotyrosine antibodies. The conclusion that the interferon-activated MBP kinase in peak 1 could be accounted for by an activated MAP kinase was also supported by the finding that fractions from Mono Q peak 1 demonstrated activity towards a MAP kinase-specific substrate. The later-eluting peak of interferon-activated MBP phosphotransferase activity appeared to be accounted for by an activated protein kinase C (PKC). This conclusion is based upon analyses of immunoblotting and immunoprecipitation experiments with antibodies to PKC and was also supported by the observed inhibition of this kinase with a PKC pseudosubstrate peptide. The interferon-stimulated PKC present in Mono Q peak 2 was active in the absence of calcium ions...

Antiviral Action of Mouse Interferon in Heterologous Cells1

Buckler, Charles E.; Baron, Samuel
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1966 Português
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Buckler, Charles E. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), and Samuel Baron. Antiviral action of mouse interferon in heterologous cells. J. Bacteriol. 91:231–235. 1966.—The antiviral action of mouse interferon in cell cultures of mouse, hamster, rat, chicken, and monkey origin was investigated. Using a vesicular stomatitis virus (VSV) plaque reduction test, we found that mouse serum interferon, assayed on closely related rat or hamster cells, exerted 5% of its homologous antiviral activity. This activity was characterized as interferon by its temperature of inactivation, trypsin sensitivity, nonsedimentability, stability at pH 2, lack of inactivation by antibody to virus, and inability to be washed off cells. In the more distantly related chicken and monkey cells, mouse interferon had less than 0.1% of its homologous activity. Conflicting reports of heterologous activity of chicken and mouse interferon preparations may result in part from the observed action of noninterferon inhibitors of vaccinia virus. These inhibitors, like interferon, are stable at pH 2. They are present in mouse serum, mouse lung extracts, and allantoic fluid, and they prevent the development of vaccinia plaques when allowed to remain in contact with cells during virus growth. Unlike interferon the inhibitors are removed by adequate washing of cells prior to virus challenge...

Induction of pulmonary indoleamine 2,3-dioxygenase by interferon.

Yoshida, R; Imanishi, J; Oku, T; Kishida, T; Hayaishi, O
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1981 Português
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Pulmonary indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase(decyclizing)] has been found to be induced (30- to 100-fold) in the mouse after a single intraperitoneal administration of bacterial endotoxin [Yoshida, R. & Hayaishi, O. (1978) Proc. Natl. Acad. Sci. USA 75, 3998-4000] or during in vivo virus infection [Yoshida, R., Urade, Y., Tokuda M. & Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. In the present study, an in vitro system with mouse lung slices was developed in which bacterial endotoxin (5 micrograms/ml)produced an induction (approximately 10-fold) of indoleamine 2,3-dioxygenase. The endotoxin was substituted by interferon from mouse L cells or mouse brain. The pulmonary enzyme activity increased almost linearly for 48 hr after addition of mouse interferon (10(4) units/ml) to lung slices. Interferon from mouse L cells or mouse brain produced a 10- to 15-fold increase in the enzyme activity, whereas that from human leukocytes was all but ineffective. The effect also was observed using highly purified L-cell interferon, prepared by poly(U) affinity column chromatography. When interferon was treated either by heat, alpha-chymotrypsin, or anti-interferon serum, such increase in the enzyme activity was diminished essentially to the same extent as seen in the antiviral activity. The increase in the enzyme activity was blocked when actinomycin D or cycloheximide was added to the slices before interferon treatment. These results suggest that the enzyme induction was produced by interferon and not by possible contaminants in the interferon preparations.

Expression of human interferon genes using the recA promoter of Escherichia coli.

Feinstein, S I; Chernajovsky, Y; Chen, L; Maroteaux, L; Mory, Y
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 11/05/1983 Português
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Interferon beta 1 and three alpha-interferon genes were cloned on Eco RI fragments isolated from a human genomic library into the Eco RI site of a plasmid containing the recA promoter of E. coli. Expression of interferon activity from cells carrying these plasmids was nalidixic acid inducible. The alpha-interferon genes were expressed only when in the same transcriptional orientation as the recA promoter while the beta 1 interferon gene was expressed in either orientation. Interferon activity was also inducibly expressed from the recA promoter in cells containing a plasmid carrying a fusion of the recA gene with the beta 1 interferon gene. This interferon activity was thirty-fold less sensitive to neutralization by polyclonal antibodies than authentic interferon, implying that the change near the amino terminus affects either antibody recognition or specific activity or both.

Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan.

Pfefferkorn, E R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1984 Português
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Treatment of human fibroblasts with human recombinant gamma interferon blocked the growth of Toxoplasma gondii, an obligate intracellular protozoan parasite. Growth of the parasite was measured by a plaque assay 7 days after infection or by the incorporation of [3H]uracil 1 or 2 days after infection. The antitoxoplasma activity induced in the host cells by gamma interferon was strongly dependent upon the tryptophan concentration of the medium. Progressively higher minimal inhibitory concentrations of gamma interferon were observed as the tryptophan concentration in the culture medium was increased. Treatment with gamma interferon did not make the cells impermeable to tryptophan. The kinetics of [3H]tryptophan uptake into the acid-soluble pools of control and gamma interferon-treated cultures were identical during the first 48 sec. Thereafter uptake of [3H]tryptophan into the acid-soluble pool of control fibroblasts reached the expected plateau after 96 sec. In contrast, uptake of [3H]tryptophan continued for at least 12 min in the gamma interferon-treated cultures. At that time, the acid-soluble pool of the gamma interferon-treated cultures contained 8 times the radioactivity of the control cultures. This continued accumulation was the result of rapid intracellular degradation of [3H]tryptophan into kynurenine and N-formylkynurenine that leaked slowly from the cells. These two metabolites were also recovered from the medium of cultures treated for 1 or 2 days with gamma interferon. Human recombinant alpha and beta interferons...

Inhibition of protein synthesis stimulates the transcription of human beta-interferon genes in Chinese hamster ovary cells.

Ringold, G M; Dieckmann, B; Vannice, J L; Trahey, M; McCormick, F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1984 Português
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Using Chinese hamster ovary (CHO) cells transfected with a plasmid carrying the human beta-interferon gene, we find that inhibitors of protein synthesis, in the absence of any other inducer, stimulate the production of interferon RNA; this effect is maintained in cells in which the plasmid sequences have been amplified 25- to 50-fold. Nuclear transcription assays show that a major effect of cycloheximide is to increase the rate of transcription of the interferon gene. This contradicts the generally accepted explanation that inhibitors of protein synthesis augment interferon production by stabilizing interferon mRNA. In addition, we have studied the effects of double stranded RNA [poly(rI) X poly(rC)] on the induction of interferon RNA in the presence and absence of cycloheximide. Our results indicate that poly(rI) X poly(rC) by itself causes a transient increase in interferon RNA; however, in the presence of cycloheximide this effect is prolonged. We do not, however, find an increase in transcription of the interferon gene(s) as an early response to poly(rI) X poly(rC). Finally, we have found that cells treated with cycloheximide or infected with Newcastle disease virus induce large amounts of a secreted 11-kDa protein. This cellular protein is not inducible by poly(rI) X poly(rC). We propose that both interferon and this 11-kDa protein belong to a family of proteins in which production is regulated in a coordinate fashion during viral inhibition of cellular protein synthesis.

Production of immune interferon by an interleukin 2-independent murine T cell line.

Benjamin, W R; Steeg, P S; Farrar, J J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1982 Português
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An interleukin 2-independent murine T cell line (BFS) was isolated that produced immune interferon after stimulation with phorbol 12-myristate 13-acetate. The BFS cell line did not produce detectable levels of interleukin 1, interleukin 2, B cell growth factor, macrophage-granulocyte colony-stimulating factor, macrophage-activating factor, or T cell replacing factor. Maximal interferon was induced 48 hr after stimulation with phorbol myristate acetate at 10-100 ng/ml. Production of interferon by phorbol myristate acetate-stimulated BFS cell cultures was synergistically increased by the addition of EL4 thymoma cell culture supernatants. BFS-derived interferon activity was sensitive to pH 2 treatment and was neutralized with antiserum to immune interferon but was resistant to heating at 56 degrees C and to treatment with antiserum to type I interferon. In addition, the interferon activity was sensitive to trypsin but resistant to RNase. BFS-derived interferon had an apparent molecular weight of 48,000 and a pI of 5.5-6.0. Each of these properties is consistent with the conclusion that the BFS cell line produces immune interferon after stimulation with phorbol myristate acetate.

Human leukocyte interferon: structural and biological relatedness to adrenocorticotropic hormone and endorphins.

Blalock, J E; Smith, E M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1980 Português
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Anti-alpha-corticotropin [anti-ACTH alpha (1-13)](also alpha-melanotropin) and anti-gamma-endorphin antisera neutralized human leukocyte interferon activity but not fibroblast interferon activity. Human leukocyte interferon was not neutralized by anti-human lutenizing hormone (lutropin) or follicle-stimulating hormone (follitropin) antisra. Conversely, antisera to human leukocyte interferon neutralized ACTH activity. The neturalization of human leukocyte interferon by anti-human leukocyte interferon serum was partially blocked by ACTH. These studies show strong antigenic relatedness among human leukocyte interferon, ACTH, and endorphins, implying that there are underlying structural similarities. Structural relatedness is shown by pepsin cleavage of ACTH activity from human leukocyte interferon. The implication for the natural functions of human leukocyte interferon are discussed.

Protective effect of low-dose interferon against neonatal murine cytomegalovirus infection.

Cruz, J R; Dammin, G J; Waner, J L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1981 Português
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Mice were injected with 10 to 5,000 reference units of interferon intraperitoneally or subcutaneously within 24 h of birth and reinoculated intraperitoneally 24 h later with 200 plaque-forming units of murine cytomegalovirus. Mock interferon and virus diluent were the control inocula. Infection of mock interferon-treated mice resulted in significant retardation of growth, accompanied by tissue injury and a depressed blastogenic response of splenic lymphocytes. Prophylactic administration of interferon prevented growth retardation and resulted in lower tissue viral titers and diminished injurious effects of the virus. Intraperitoneal inoculation of interferon was more protective than was subcutaneous, and 10 U of interferon was often as effective as 5,000 U. Accelerated maturation and enhanced activity of lymphoid elements were observed histologically in spleens and lymph nodes of interferon-treated mice; supportive of these findings was the greater incorporation of [3H]thymidine of splenocytes from interferon-treated mice. The protective effect of interferon may, therefore, be due to stimulation or accelerated maturation of cellular immune functions.

Synthesis of type C virus particles from murine-cultured cells induced by iododeoxyuridine. V. Effect of interferon and its interaction with dexamethasone.

Wu, A M; Schultz, A; Gallo, R C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1976 Português
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Previous studies have shown that in certain cell systems dexamethasone may enhance the production of type C viruses. Conversely, interferon has been shown to inhibit their production. Both appear to exert their influence late in the viral replication cycle rather than on the synthesis of viral-specific RNA. In this report dexamethasone and interferon have been used to study some aspects of the mechanisms involved in the synthesis of type C viruses in murine K-BALB cells following induction of virus production by iododeoxyuridine. Interferon inhibited production of xenotropic type C virus induced by iododeoxyuridine from K-BALB cells both in the absence and presence of dexamethasone, but it did not affect production of N-tropic type C virus. Exposure of the cells to interferon for longer than 12 h was required for maximum effect. Two types of inhibitory effects were observed: one diminished by dexamethasone when the steroid was added 24 h after interferon removal, and the second resistant to dexamethasone. The concentration of intracellular group-specific antigen was diminshed after interferon and increased after dexamethasone exposure. When induced cells were treated with both interferon and dexamethasone, the intracellular group-specific protein concentration was slightly increased...

Control of Interferon Synthesis: Effect of Diethyl-aminoethyl-Dextran on Induction by Polyinosinic-Polycytidylic Acid

Vilček, Jan; Barmak, Sandra L.; Havell, Edward A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1972 Português
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Interferon production in cultures of rabbit kidney cells (RKC) stimulated with 10 to 250 μg of polyinosinic-polycytidylic acid (poly I·poly C) per ml peaked at 3 to 4 hr after the exposure of cells to inducer and rapidly declined thereafter. On the other hand, RKC stimulated with poly I·poly C (10 or 2 μg/ml) in the presence of diethylaminoethyl (DEAE)-dextran (100 or 20 μg/ml, respectively) produced a protracted interferon response, with the release of interferon continuing for over 24 hr. The kinetics of interferon production in RKC stimulated with lower concentrations of the mixture of poly I·poly C and DEAE-dextran were similar to the response produced by poly I·poly C alone (10 to 250 μg/ml). Only the responses that terminated early were paradoxically enhanced by treatment with low doses of actinomycin D or with cycloheximide. Cells stimulated with 50 μg of poly I·poly C/ml showed hyporesponsiveness to a second interferon induction with poly I·poly C when restimulated 7 hr after primary induction. This hyporesponsiveness could be overcome by restimulating with higher concentrations of the poly I·poly C-DEAE-dextran complex. The results are compatible with the hypothesis that the early termination of interferon production and hyporesponsiveness to repeated induction with poly I·poly C are due to a cellular repressor exerting negative control on interferon synthesis...

Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier

Lazear, Helen M.; Daniels, Brian P.; Pinto, Amelia K.; Huang, Albert C.; Vick, Sarah C.; Doyle, Sean E.; Gale, Michael; Klein, Robyn S.; Diamond, Michael S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 22/04/2015 Português
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Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1−/− mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1−/− mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1−/− mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance...

Interferon-γ Inhibits Ebola Virus Infection

Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.; Monick, Martha M.; Maury, Wendy
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 12/11/2015 Português
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Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection...

Interferon-induced proteins in human fibroblasts and development of the antiviral state.

Rubin, B Y; Gupta, S L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1980 Português
Relevância na Pesquisa
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Treatment of human fibroblasts with interferon induces the synthesis of several proteins, as detected by incorporation of [35S]methionine followed by analysis of cell extracts by polyacrylamide gel electrophoresis. The induction of these proteins had features in common with the development of the antiviral effect of interferon, such as (i) sensitivity to actinomycin D and cycloheximide when these compounds were added together with interferon, (ii) insensitivity to actinomycin D if the actinomycin D was added 2 h after the addition of interferon, (iii) similar dependence on interferon concentration, and (iv) species specificity for interferon. When interferon treatment was given in the presence of cycloheximide and actinomycin D was added before the removal of cycloheximide, all four proteins were induced, thus suggesting that their inductions are coordinated. Labeling for 2-h periods at varying time intervals after the addition of interferon revealed that the synthesis of these proteins was induced within a few hours, peaked at different time intervals, and was soon followed by a marked decline, suggesting that the mRNA's for these proteins have short half-lives. Moreover, this decline occurred despite the fact that the cells were continuously exposed to interferon...

Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo.

Zoumbos, N C; Gascon, P; Djeu, J Y; Young, N S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1985 Português
Relevância na Pesquisa
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We have investigated interferon as a mediator of hematopoietic suppression in bone marrow failure. Interferon production by stimulated peripheral blood mononuclear cells from patients with aplastic anemia was significantly higher than that observed in controls; spontaneous interferon production by these cells was also high for more than half of aplastic anemia patients. Circulating interferon, not detectable in normal individuals, was detected in 10 of 24 patients. Interferon is a potent inhibitor of hematopoietic cell proliferation and, therefore, may be the mediator of suppression in many in vitro models employing patients' cells and sera. The possible pathogenic importance of interferon in aplastic anemia was suggested by an increase in hematopoietic colony formation in vitro after exposure of bone marrow cells to antiinterferon antisera (277 +/- 71% increase for patients compared to 1.6 +/- 1.6% for normal individuals). Interferon levels in the bone marrow sera of aplastic anemia patients were high (mean = 203 international units (IU)/ml, n = 8), even in comparison to circulating levels in the same patients. Normal bone marrow sera also contained measurable interferon but at lower levels (41 IU/ml, n = 16), indicating that interferon may be a normal bone marrow product. High concentration of bone marrow interferon...