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Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor.

Gutch, M J; Daly, C; Reich, N C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/12/1992 Português
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The signal transduction pathway of alpha interferon utilizes tyrosine phosphorylation to transmit a signal generated at the cell surface to the transcriptional machinery in the nucleus. Activation of the interferon pathway initiates with the binding of alpha interferon to its cell surface receptor. The ligand-receptor complex signals the activation of a latent cytoplasmic transcription factor. The active form of the interferon-stimulated gene factor (ISGF3) is phosphorylated on tyrosine residues. ISGF3 subsequently translocates to the nucleus and binds to a DNA sequence, the interferon-stimulated response element, found within the promoter of inducible genes. ISGF3 is a multicomponent factor consisting of four proteins of 113 kDa, 91 kDa, 84 kDa, and 48 kDa. Three proteins consistent with sizes of 113 kDa, 91 kDa, and 84 kDa copurify with ISGF3 and are phosphorylated on tyrosine residues after stimulation by alpha interferon. Tyrosine phosphorylation is essential for activation of ISGF3. Genistein, a tyrosine kinase inhibitor, blocks the appearance of ISGF3 and blocks the transcriptional stimulation of interferon-induced genes. This study shows that tyrosine phosphorylation provides a link between the interferon-receptor complex at the plasma membrane and specific activation of gene expression in the nucleus.

Interferon-alpha selectively activates the beta isoform of protein kinase C through phosphatidylcholine hydrolysis.

Pfeffer, L M; Strulovici, B; Saltiel, A R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1990 Português
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The early events that occur after interferon binds to discrete cell surface receptors remain largely unknown. Human leukocyte interferon (interferon-alpha) rapidly increases the binding of [3H]phorbol dibutyrate to intact HeLa cells (ED50 = 100 units/ml), a measure of protein kinase C activation, and induces the selective translocation of the beta isoform of protein kinase C from the cytosol to the particulate fraction of HeLa cells. The subcellular distribution of the alpha and epsilon isoforms is unaffected by interferon-alpha treatment. Activation of protein kinase C by phorbol esters mimics the inhibitory action of interferon-alpha on HeLa cell proliferation and down-regulation of protein kinase C blocks the induction of antiviral activity by interferon-alpha in HeLa cells. Increased phosphatidylcholine hydrolysis and phosphorylcholine production is accompanied by diacylglycerol production in response to interferon. However, inositol phospholipid turnover and free intracellular calcium concentration are unaffected. These results suggest that the transient increase in diacylglycerol, resulting from phosphatidylcholine hydrolysis, may selectively activate the beta isoform of protein kinase C. Moreover, the activation of protein kinase C is a necessary element in interferon action on cells.

Cytomegalovirus Activates Interferon Immediate-Early Response Gene Expression and an Interferon Regulatory Factor 3-Containing Interferon-Stimulated Response Element-Binding Complex

Navarro, Lorena; Mowen, Kerri; Rodems, Steven; Weaver, Brian; Reich, Nancy; Spector, Deborah; David, Michael
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/1998 Português
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Interferon establishes an antiviral state in numerous cell types through the induction of a set of immediate-early response genes. Activation of these genes is mediated by phosphorylation of latent transcription factors of the STAT family. We found that infection of primary foreskin fibroblasts with human cytomegalovirus (HCMV) causes selective transcriptional activation of the alpha/beta-interferon-responsive ISG54 gene. However, no activation or nuclear translocation of STAT proteins was detected. Activation of ISG54 occurs independent of protein synthesis but is prevented by protein tyrosine kinase inhibitors. Further analysis revealed that HCMV infection induced the DNA binding of a novel complex, tentatively called cytomegalovirus-induced interferon-stimulated response element binding factor (CIF). CIF is composed, at least in part, of the recently identified interferon regulatory factor 3 (IRF3), but it does not contain the STAT1 and STAT2 proteins that participate in the formation of interferon-stimulated gene factor 3. IRF3, which has previously been shown to possess no intrinsic transcriptional activation potential, interacts with the transcriptional coactivator CREB binding protein, but not with p300, to form CIF. Activating interferon-stimulated genes without the need for prior synthesis of interferons might provide the host cell with a potential shortcut in the activation of its antiviral defense.

Interferons, Interferon Inducers, and Interferon-Ribavirin in Treatment of Flavivirus-Induced Encephalitis in Mice

Leyssen, Pieter; Drosten, Christian; Paning, Marcus; Charlier, Nathalie; Paeshuyse, Jan; De Clercq, Erik; Neyts, Johan
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2003 Português
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We evaluated the prophylactic and therapeutic efficacy of interferon α-2b, pegylated interferon α-2b, poly(I · C), and Ampligen against Modoc virus encephalitis in an animal model for flavivirus infections. All compounds significantly delayed virus-induced morbidity (paralysis) and mortality (due to progressive encephalitis). Viral load (as measured on day 7 postinfection) was significantly reduced by 80 to 100% in the serum, brain, and spleen in mice that had been treated with either interferon α-2b, pegylated interferon α-2b, poly(I · C), or Ampligen. We also studied whether a combination of interferon α-2b and ribavirin (presently the standard therapy for the treatment of infections with hepatitis C virus) would be more effective than treatment with interferon alone. However, ribavirin did not enhance the inhibitory effect of interferon therapy in this animal model for flavivirus infections.

Attenuation of gamma interferon-induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani: selective inhibition of signaling through Janus kinases and Stat1.

Nandan, D; Reiner, N E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1995 Português
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The induction of gene transcription in response to gamma interferon is impaired in mononuclear phagocytes infected with Leishmania donovani, and the mechanisms involved are not fully understood. The changes in gene expression brought about by gamma interferon are thought to involve transient increases in the activities of cellular protein tyrosine kinases, including the Janus kinases Jak1 and Jak2, leading to tyrosine phosphorylation of the transcription factor Stat1. To investigate the mechanisms accounting for the impaired responses to gamma interferon, a model system for examining overall changes in protein tyrosine phosphorylation, activation of Jak1 and Jak2 and phosphorylation of Stat1 was developed in phorbol 12-myristate 13-acetate-differentiated U-937 cells. Analysis of whole-cell lysates by antiphosphotyrosine immunoblotting showed that incubation with gamma interferon brought about specific increases in phosphotyrosine labeling of several proteins. Increased labeling of these proteins occurred to similar extents in control cells and in cells that had been infected with L. donovani for 16 h. Jak1, Jak2, and Stat1 were immunoprecipitated from control and interferon-treated cells, and tyrosine phosphorylation of these proteins...

Production of high levels of human leukocyte interferon from a continuous human myeloblast cell culture.

Familletti, P C; McCandliss, R; Pestka, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1981 Português
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A myeloblast cell line has proved to be an excellent source of human leukocyte interferon. These cells, primed with interferon and induced with Sendai virus, produced optimal levels of human leukocyte interferon. The cells grew readily in spinner flasks and in medium containing horse serum. Interferon production over several months yielded an average titer of 2 X 10(5) reference units of interferon per 10(7) cells. The interferon produced by these cells appeared to be predominantly species of human leukocyte interferon. Since these cells seemed to consist of myeloblasts, it is clear that cells other than B-lymphocytes can produce leukocyte interferon.

Alpha interferon and acyclovir treatment of herpes simplex virus in lymphoid cell cultures.

Hammer, S M; Kaplan, J C; Lowe, B R; Hirsch, M S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1982 Português
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The T-lymphoblastoid cell line CEM, persistently infected with herpes simplex virus type 1, has been used to examine the antiviral efficacy of human alpha interferon and acyclovir, both alone and in combination. Acyclovir and interferon each produced dose-dependent decreases in virus titer at concentration ranges of 1 to 100 microM (approximately 0.225 to 22.5 micrograms/ml) and 10 to 10,000 U/Ml, respectively. Mean reductions in titer of 1.9 and 4.2 log10 PFU/ml were observed with 100 microM acyclovir and 10,000 U of interferon per ml, respectively, on day 10 of treatment. The combination of 100 microM acyclovir and 10,000 U of interferon per ml produced the most rapid fall in virus titer of all regimens examined and elimination of infections virus by day 7. Prolonged treatment (greater than 10 days) with acyclovir or alpha interferon was accompanied by a gradual return of virus titer to control levels despite the continuous presence of drug. Virus preparations isolated from such cultures were tested for antiviral agent sensitivity by a plaque reduction method. Acyclovir-exposed isolates were found to be acyclovir resistant, with 50% inhibitory doses of greater than 200 microM, and to be thymidine kinase deficient. Alpha interferon-exposed isolates were not interferon resistant. These results suggest that...

Isolation of highly fusogenic variants of simian virus 5 from persistently infected cells that produce and respond to interferon.

Young, D F; Didcock, L; Randall, R E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1997 Português
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A series of experiments were undertaken to examine how interferon and neutralizing antibodies influence the ability of simian virus 5 (SV5) (strain W3) to establish and maintain persistent infections in murine cells. In contrast to the rapid decline in SV5 protein synthesis observed in murine BALB/c fibroblasts (BF cells), which produce and respond to interferon, between 24 and 48 h postinfection there was no inhibition of virus protein synthesis in MSFI- cells, skin fibroblasts derived from alpha/beta-interferon receptor knockout BALB/c mice. Furthermore, the addition of anti-interferon antibodies to the culture medium of infected BF cells significantly reduced the observed decline in virus protein synthesis. Following infection of untreated BF cells, the majority replicated virus but survived the infection and eventually cleared the virus after 8 to 15 days. However, not all the cells were cured, and the cultures became persistently infected. Upon passage of persistently infected cultures, the virus fluxed between active and repressed states as a consequence of interferon production. This resulted in a balance being reached in which only 5 to 20% of the cells were infected at any one time. After 30 passages of the persistently infected cells...

Inhibitory Effect of a Triterpenoid Compound, with or without Alpha Interferon, on Hepatitis C Virus Infection▿†

Watanabe, Takako; Sakamoto, Naoya; Nakagawa, Mina; Kakinuma, Sei; Itsui, Yasuhiro; Nishimura-Sakurai, Yuki; Ueyama, Mayumi; Funaoka, Yusuke; Kitazume, Akiko; Nitta, Sayuri; Kiyohashi, Kei; Murakawa, Miyako; Azuma, Seishin; Tsuchiya, Kiichiro; Oooka, Shiny
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2011 Português
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A lack of patient response to alpha interferon (α-IFN) plus ribavirin (RBV) treatment is a major problem in eliminating hepatitis C virus (HCV). We screened chemical libraries for compounds that enhanced cellular responses to α-IFN and identified a triterpenoid, toosendanin (TSN). Here, we studied the effects and mechanisms of action of TSN on HCV replication and its effect on α-IFN signaling. We treated HCV genotype 1b replicon-expressing cells and HCV-J6/JFH-infected cells with TSN, with or without α-IFN, and the level of HCV replication was quantified. To study the effects of TSN on α-IFN signaling, we detected components of the interferon-stimulated gene factor 3 (ISGF3), phosphorylated signal transducer and activator of transcription 1 (STAT1), and STAT2 by Western blotting analysis; expression levels of mRNA of interferon regulatory factor 9 using real-time reverse transcription-PCR (RT-PCR); and interferon-stimulated response element reporter activity and measured the expression levels of interferon-inducible genes for 2′,5′-oligoadenylate synthetase, MxA, protein kinase R, and p56 using real-time RT-PCR. TSN alone specifically inhibited expression of the HCV replicon (50% effective concentration = 20.6 nM, 50% cytotoxic concentration > 3 μM...

Interferon Impedes an Early Step of Hepatitis Delta Virus Infection

Han, Ziying; Nogusa, Shoko; Nicolas, Emmanuelle; Balachandran, Siddharth; Taylor, John
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 19/07/2011 Português
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Hepatitis delta virus (HDV) infects hepatocytes, the major cell type of the liver. Infection of the liver may be either transient or chronic. The prognosis for patients with chronic HDV infection is poor, with a high risk of cirrhosis and hepatocellular carcinoma. The best antiviral therapy is weekly administration for at least one year of high doses of interferon alpha. This efficacy of interferon therapy has been puzzling in that HDV replication in transfected cell lines is reported as insensitive to administration of interferon alpha or gamma. Similarly, this study shows that even when an interferon response was induced by transfection of poly(IC) into a cell line, HDV RNA accumulation was only modestly inhibited. However, when the HDV replication was initiated by infection of primary human hepatocytes, simultaneous addition of interferons alpha or gamma at 600 units/ml, a concentration comparable to that achieved in treated patients, the subsequent HDV RNA accumulation was inhibited by at least 80%. These interferon treatments were shown to produce significant time-dependent increases of host response proteins such as for Stat-1, phosphoStat-1, Mx1/2/3 and PKR, and yet interferon pretreatment of hepatocytes did not confer an increased inhibition of HDV replication over interferon treatment at the time of (or after) infection. These and other data support the interpretation that interferon action against HDV replication can occur and is largely mediated at the level of entry into primary human hepatocytes. Thus in vivo...

The Anti-interferon Activity of Conserved Viral dUTPase ORF54 is Essential for an Effective MHV-68 Infection

Leang, Ronika Sitapara; Wu, Ting-Ting; Hwang, Seungmin; Liang, Lidia T.; Tong, Leming; Truong, Jennifer T.; Sun, Ren
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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Gammaherpesviruses such as KSHV and EBV establish lifelong persistent infections through latency in lymphocytes. These viruses have evolved several strategies to counteract the various components of the innate and adaptive immune systems. We conducted an unbiased screen using the genetically and biologically related virus, MHV-68, to find viral ORFs involved in the inhibition of type I interferon signaling and identified a conserved viral dUTPase, ORF54. Here we define the contribution of ORF54 in type I interferon inhibition by ectopic expression and through the use of genetically modified MHV-68. ORF54 and an ORF54 lacking dUTPase enzymatic activity efficiently inhibit type I interferon signaling by inducing the degradation of the type I interferon receptor protein IFNAR1. Subsequently, we show in vitro that the lack of ORF54 causes a reduction in lytic replication in the presence of type I interferon signaling. Investigation of the physiological consequence of IFNAR1 degradation and importance of ORF54 during MHV-68 in vivo infection demonstrates that ORF54 has an even greater impact on persistent infection than on lytic replication. MHV-68 lacking ORF54 expression is unable to efficiently establish latent infection in lymphocytes...

The Treatment Response of Chronically Hepatitis C Virus-Infected Patients Depends on Interferon Concentration but Not on Interferon Gene Expression in Peripheral Blood Mononuclear Cells

François, Catherine; Coulouarn, Cédric; Descamps, Véronique; Castelain, Sandrine; Brochot, Etienne; Baron, Agnès; Duchaussoy, Isabelle; Capron, Dominique; Nguyen-Khac, Eric; Duverlie, Gilles
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2012 Português
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The current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined therapy. The interferon concentration was measured in serum by a bioassay. The expression of 93 interferon-regulated genes in peripheral blood mononuclear cells was quantified by real-time quantitative reverse transcription-PCR (RT-PCR) before and after 1 month of treatment. The interferon concentration in the serum was significantly lower in nonresponders than in sustained virological responders. Moreover, a significant correlation was identified between interferon concentration and interferon exposition as well as body weight. The analysis of interferon-inducible genes in peripheral blood mononuclear cells among the genes tested did not permit the prediction of treatment outcome. In conclusion, the better option seems to be to treat patients with weight-adjusted PEG-IFN doses, particularly for patients with high weight who are treated with PEG-IFN-α2a. Although the peripheral blood mononuclear cell samples are the easiest to obtain...

Interferon–β Induces Hepatocyte Growth Factor in Monocytes of Multiple Sclerosis Patients

Molnarfi, Nicolas; Benkhoucha, Mahdia; Bjarnadóttir, Kristbjörg; Juillard, Catherine; Lalive, Patrice H.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 14/11/2012 Português
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Interferon-β is a first-line therapy used to prevent relapses in relapsing-remitting multiple sclerosis. The clinical benefit of interferon-β in relapsing-remitting multiple sclerosis is attributed to its immunomodulatory effects on inflammatory mediators and T cell reactivity. Here, we evaluated the production of hepatocyte growth factor, a neuroprotective and neuroinflammation-suppressive mediator, by peripheral blood mononuclear cells collected from interferon-β−treated relapsing-remitting multiple sclerosis patients, relapsing remitting multiple sclerosis patients not treated with interferon-β, and healthy volunteers. Using intracellular flow cytometry analysis, increased production of hepatocyte growth factor was observed in circulating CD14+ monocytes from patients undergoing long-term treatment with interferon-β versus untreated patients. Complementary in vitro studies confirmed that treatment with interferon-β induced rapid and transient transcription of the hepatocyte growth factor gene in CD14+ monocytes and that intracellular and secreted monocytic hepatocyte growth factor protein levels were markedly stimulated by interferon-β treatment. Additional exploration revealed that “pro-inflammatory” (CD14+CD16+) monocytes produced similar levels of hepatocyte growth factor in response to interferon-β as “classical” (CD14+CD16−) monocytes...

Desordens tireoideanas em pacientes portadores de Hepatite C

Santos, Sandra Regina Xavier
Fonte: Universidade Federal de Uberlândia Publicador: Universidade Federal de Uberlândia
Tipo: Dissertação
Português
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Interferon alfa e Ribaverina são as drogas de primeira escolha para o tratamento da Hepatite C, porém podem desencadear desordens tireoideanas como uma das principais complicações. Diversos estudos têm mostrado uma prevalência muito variável (1% a 35%) desta associação influenciada pela distribuição geográfica, genética e consumo de iodo da população. O objetivo deste estudo foi analisar as desordens tireoideanas em pacientes portadores de Hepatite C em tratamento ou não com Interferon alfa e Ribaverina. Foram avaliadas as frequências e o padrão das desordens tireoideanas em 25 pacientes com Hepatite C em tratamento com Interferon alfa e Ribaverina (G1), 62 pacientes com Hepatite C sem tratamento (G2) e 82 pacientes sem Hepatite C (Grupo Controle), por meio da dosagem do TSH, anticorpos antiperoxidase (anti-TPO) e antitireoglobulina (ATG). O hipotiroidismo foi mais frequente nos pacientes portadores de Hepatite C em tratamento (36%), enquanto a frequência de anticorpos antitireoideanos não foi diferente nos três grupos estudados respectivamente (12% em G1; 8,06% em G2; 17,07% no grupo Controle), com p= 0,955. Não foi possível demonstrar a maior frequência de Doença Autoimune de Tireóide em pacientes portadores de Hepatite C em tratamento com Interferon alfa e Ribaverina...

Interferon induction by adenoviruses.

Béládi, I.; Pusztai, R.; Bakay, M.; Mucsi, I.; Taródi, B.
Fonte: BMJ Group Publicador: BMJ Group
Tipo: Artigo de Revista Científica
Publicado em /02/1979 Português
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All human, simian, bovine and avian adenovirus types tested so far and the canine hepatitis virus induce interferon production in chick cells. This finding indicated this property to be characteristic for viruses belonging to the adenovirus group. Trypsin treatment, which had no effect upon the infectivity, diminished or eliminated the interferon-inducing abilities of crude adenoviruses, and thus the need for a trypsin-sensitive protein in interferon induction was suggested. T antigen and interferon were formed simultaneously in chick embryo fibroblast cells infected with human adenovirus type 12, and therefore the adenovirus-specific T antigen was resistant to the action of endogenous interferon synthetized by the same cells. In chicks inoculated with human types, the appearance of interferon was biphasic: an 'early' and a 'late' interferon could be demonstrated with maximum titre 4 and 10 hr, respectively, after virus infection. In chicks infected with adenoviruses, first interferon production and then a decreased primary immune response to sheep red blood cells was observed. It was assumed that in adenovirus-infected chicks the interferon produced by viral stimulus resulted in a transient immunosuppression.

Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor confers resistance to the antiproliferative effect of interferon-alpha.

Flowers, C. C.; Flowers, S. P.; Nabel, G. J.
Fonte: The Feinstein Institute for Medical Research Publicador: The Feinstein Institute for Medical Research
Tipo: Artigo de Revista Científica
Publicado em /06/1998 Português
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BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a 442 amino acid polypeptide-designated viral interferon regulatory factor (vIRF) that displays homology to members of the interferon regulatory factor (IRF) family that bind to consensus interferon sequences and transactivate cellular genes that can modulate growth inhibition. Studies were conducted to determine whether vIRF affects the growth suppression mediated by interferon-alpha (IFN-alpha) in a human B lymphocyte cell line. MATERIALS AND METHODS: The human B lymphocyte cell line Daudi, which is sensitive to the antiproliferative effects of IFN-alpha, was stably transfected to express vIRF, and the proliferative response of vIRF expressing cells to IFN-alpha was compared with controls. The effect of vIRF on IRF- 1 transactivation was analyzed by co-transfection of an IFN-alpha-responsive chloramphenicol acetyltransferase reporter and expression plasmids encoding IRF-1 and vIRF. Electrophoretic mobility shift assays were conducted to determine whether vIRF interferes with the DNA binding activity of IRF-1. RESULTS: Daudi human B lymphocyte cells expressing vIRF were resistant to the antiproliferative effects of IFN-alpha, whereas wild-type Daudi or Daudi cells transformed with vector DNA were growth inhibited by IFN-alpha. The activation of an interferon-responsive reporter by IFN-alpha or IRF-1 was repressed by expression of vIRF. IRF-1 DNA binding activity was unaffected by vIRF...

Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest.

Tiefenbrun, N; Melamed, D; Levy, N; Resnitzky, D; Hoffman, I; Reed, S I; Kimchi, A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1996 Português
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Alpha interferon is a potent growth inhibitor of Daudi Burkitt's lymphoma cells. We show here that alpha-interferon signaling interacted simultaneously with several components of the basic cell cycle machinery, causing cells to enter into a state that had many features characteristic of the G0 state. Within a few hours after alpha-interferon treatment, cyclin D3 mRNA and protein levels dropped to undetectable levels and, in parallel, the activities of cyclin A- and cyclin E-associated kinases were significantly reduced. The latter resulted from the rapid alpha-interferon-mediated elimination of cdc25A, a phosphatase that is required for antagonism of negative tyrosine phosphorylation of cdk2 in cyclin-cdk complexes. This regulation represents a novel mechanism through which an external inhibitory cytokine interacts with the cell cycle machinery. At later time points after alpha-interferon treatment, the levels of the 55-kDa slowly migrating hyperphosphorylated form of cyclin E and of cyclin A were also reduced. The antiproliferative effects were reversible, and cultures from which alpha interferon was removed reentered S phase after a lag that typically corresponded to approximately two doubling times. During this lag period, the expression of cyclin D3 and cyclin A...

Differential antiviral effects of interferon in three murine cell lines.

Sen, G C; Herz, R E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1983 Português
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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...

Enhancement by interferon of membrane HLA antigens in patients with combined immunodeficiency with defective HLA expression.

Durandy, A; Virelizier, J L; Griscelli, C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1983 Português
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Since interferon is known to enhance HLA A-B expression on lymphocytes from normal donors, we have tested the hypothesis that interferon could reverse the defective membrane expression of HLA antigens observed in some patients with combined immunodeficiency. Leucocytes from four patients with this syndrome, after overnight incubation with preparations of interferon, showed a clear enhancement in the percentage of cells bearing HLA A-B-C and beta 2 microglobulin (but not HLA-DR) antigens as detected by membrane immunofluorescence. Functional HLA-A and B antigens also appeared on patients' T cell blasts treated with interferon, as shown by the ability of these blasts to be destroyed by specific cytotoxic T lymphocytes. Both alpha and beta human interferons were effective. These effects were shown to be mediated by interferon (but not contaminants in our preparations) by the use of specific antiserum to interferon. It is likely that interferon acts on HLA synthesis, since in vitro addition of drugs known to inhibit nucleic acid or protein synthesis completely abolished the enhancing effect of interferon on membrane HLA expression. Interferons can therefore modulate leucocyte HLA expression and synthesis in patients with defective expression of these antigens...

Interferon-α 2b combined with daily ketoprofen administration improves virological response in chronic hepatitis C: a prospective and randomised trial

Munoz, A; Levi, D; Podesta, A; Gorin, J; Gonzalez, J; Bartellini, M; Munne, M; Cabanne, A; Flichman, D; Terg, R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/2000 Português
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BACKGROUND—Less than 15% of patients with chronic hepatitis C show a sustained virological response to interferon treatment.
AIM—To evaluate the efficacy and safety of different doses of ketoprofen combined with interferon-α 2b in the treatment of chronic hepatitis C.
PATIENTS/METHODS—Seventy compensated patients with chronic hepatitis C received interferon-α 2b 3 million units three times a week for six months. They were randomly assigned to: group 1 (n = 23), interferon-α 2b alone; group 2 (n = 23), interferon-α 2b plus 200 mg ketoprofen three times a week; group 3 (n = 24), interferon-α 2b plus 200 mg ketoprofen twice a day. Complete and sustained responses were defined as normal serum alanine aminotransferase levels and negative serum hepatitis C virus RNA at six and 12 months respectively.
RESULTS—Complete and sustained responses were similar in groups 1 and 2: 10% v 5% and 5% v 0% respectively. In group 3, complete response was 29% (p = 0.13 v group 1 and p = 0.04 v group 2) and sustained response was 26% (p = 0.07 v group 1 and p = 0.01 v group 2). Overall, adverse events were similar in the three groups. However, 'flu-like syndrome was less common in group 2 (30%) and group 3 (37%) than in group 1 (77%) (p = 0.01).
CONCLUSIONS—Twice daily ketoprofen administration combined with interferon-α 2b produced an increase in complete and sustained responses. Although the combination of interferon-α 2b with ketoprofen was well tolerated and decreased the incidence of 'flu-like syndrome...