Virus interferon pathway

The naming of cats—and alpha-interferons. Floyd-Smith G. J Cell Biochem. Human T cells elicit IFN-alpha secretion from dendritic cells following cell to cell interationis.

Eur J Immunol. Sequence variability of Borna disease virus: resistance to superinfection may contribute to high genome stability in persistently infected cells. Expression of hepatitis C virus proteins interferes with the antiviral action of interferon independently of PKR-mediated control of protein synthesis.

Human MxA protein inhibits tick-borne Thogoto virus but not Dhori virus. Prevention of vertebrate neuronal death by the crmA gene. Galabru J, Hovanessian A G. Autophosphorylation of the protein kinase dependent on double-stranded RNA.

Gale M, Katze M G. Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. Pharmacol Ther. Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Antiapoptotic and oncogenic potentials of hepatitis C virus are linked to interferon resistance by viral repression of the PKR protein kinase.

Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Translational control of viral gene expression in eukaryotes. Microbiol Mol Biol Rev. An interferon-gamma-activated site GAS is necessary for full expression of the mouse iNOS gene in response to interferon-gamma and lipopolysaccharide.

The role of interferon in influenza virus tissue tropism. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Sendai virus C proteins must interact directly with cellular components to interfere with interferon action. Sendai virus C proteins counteract the interferon-mediated induction of an antiviral state. Analysis of human chromosome correlation of physical and cytogenetic maps: gene and CpG island distributions.

Interferon-gamma protects against herpes simplex virus type 1-mediated neuronal death. Human RNA specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon-inducible. Cell growth regulatory and antiviral effects of the P69 isozyme of A synthetase.

Structure-function relationships. Biologic consequences of Stat1-independent IFN signaling. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med. Genes Dev. Role of interferon and interferon regulatory factors in early protection against Venezuelan equine encephalitis virus infection. Kinetics of cytokine expression and regulation of host protection following infection with molecularly cloned Venezuelan equine encephalitis virus.

Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol. Cytokine-mediated control of viral infections. Cytotoxix T lymphocyes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver.

Viral clearance without destruction of infected cells during acute HBV infection. Guo J, Sen G C. Characterization of the interaction between the interferon-induced protein P56 and the Int6 protein encoded by a locus of insertion of the mouse mammary tumor virus.

A new pathway of translational regulation mediated by eukaryotic initiation factor 3. Induction of human protein P56 by interferon, double-stranded RNA, or virus infection. Mx proteins: mediators of innate resistance to RNA viruses.

Hardwick J M. Viral interference with apoptosis. Cell Dev Biol. A dominant negative mutant of A-dependent RNase suppresses antiproliferative and antiviral effects of interferon. Mutant influenza viruses with a defective NS1 protein cannot block the activation of PKR in infected cells.

The gamma 1 Heim M H. J Receptor Signal Transduction Res. Triggering the interferon response: the role of IRF-3 transcription factor. Hoofnagle J H. Therapy of acute and chronic viral hepatitis. Adv Intern Med. Horvath C M. STAT proteins and transcriptional responses to extracellular signals. Hovanessian A G, Galabru J. The double- stranded RNA-dependent protein kinase is also activated by heparin. Identification of kd and kd forms of A synthetase in interferon-treated human cells by specific monoclonal antibodies.

Characterization of and kDa forms of A-synthetase from interferon-treated human cells. Immune response in mice that lack the interferon-gamma receptor. A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses.

Isaacs A, Lindenmann J. Virus interference. The interferon. When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA.

J Cell Sci. Identification of the murine Mx2 gene: interferon-induced expression of the Mx2 protein from the feral mouse gene confers resistance to vesicular stomatitis virus. Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons. New mouse model for dengue virus vaccine testing. Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Katze M G. Regulation of the interferon-induced PKR: can viruses cope?

Functional expression and RNA binding analysis of the interferon-induced, double-stranded RNA-activated 68, M r protein kinase in a cell-free system. Kerr I M. The A system: a personal view. Kim S, Ponka P. Effects of interferon-gamma and lipopolysaccharide on macrophage iron metabolism are mediated by nitric oxide-induced degradation of iron regulatory protein 2.

Genes Cells. IRF-1 induced cell growth inhibition and interferon induction requires the activity of the protein kinase PKR. Virus-host cell interactions. Kochs G, Haller O. Sendai virus blocks alpha interferon signaling to signal transducers and activators of transcription.

Kon N, Suhadolnik R J. Kostura M, Mathews M B. Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product. Mechanism of interferon action: functional characterization of positive and negative regulatory domains that modulate transcriptional activation of the human RNA-dependent protein kinase Pkr promoter. Structural organization of the human gene PKR encoding an interferon-inducible RNA-dependent protein kinase and differences from its mouse homolog.

Mechanism of interferon action. Mechanism of interferon action: identification of essential positions within the novel base-pair KCS element required for transcriptional activation of the RNA-dependent protein kinase pkr gene. Proc Natl Acad Sci. Regulated nuclear-cytoplasmic localization of interferon regulatory factor 3, a subunit of double-stranded RNA-activated factor 1. Kumar M, Carmichael G G. Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcript.

Mol Biol Evol. Mutagenic analysis of double-stranded RNA adenosine deaminase, a candidate enzyme for RNA editing of glutamate-gated ion channel transcripts. The molecular biology of hepatitis delta virus.

Annu Rev Biochem. The Ifi genes: an emerging family of IFN-inducible genes. Mechanism of interferon action: characterization of the sites of phosphorylation in the interferon-induced phosphoprotein P1 from mouse fibroblasts: evidence for two forms of P1.

Interferon regulatory factor subcellular localization is determined by a bipartite nuclear localization signal in the DNA-binding domain and interaction with cytoplasmic retention factors.

Differential regulation of constitutive major histocompatibility complex class I expression in T and B lymphocytes. Lee S B, Esteban M. The interferon-induced double-stranded RNA-activated human p68 protein kinase inhibits the replication of vaccinia virus.

Mechanism of Interferon Action. Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene.

Gamma interferon impedes the establishment of herpes simplex virus type 1 latent infection but has no impact on its maintenance or reactivation in mice. Lengyel P. Tumor-suppressor genes: news about the interferon connection. The interferon-activatable gene cluster: from structure toward function. Semin Virol. Restoration of interferon responses of adenovirus E1A-expressing HT ell lines by overexpression of p48 protein.

Jaks and STATs: biological implications. Levy D E. Physiological significance of STAT proteins: investigations through gene disruption in vivo.

Cell Mol Life Sci. A role for the A system in attenuation of the interferon response. Double-stranded RNA-specific adenosine deaminase: nucleic acid binding properties. Liu Y, Samuel C E. Mechanism of interferon action: functionally distinct RNA-binding and catalytic domains in the interferon-inducible, double-stranded RNA-specific adenosine deaminase.

Liu T, Chambers T J. Targeted disruption of the interferon gamma receptor 2 gene results in severe immune defects in mice. J Med Virol. Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the eIF-2 translation initiation factor.

Pegylated alpha interferon is an effective treatment for virulent venezuelan equine encephalitis virus and has profound effects on the host immune response to infection. Maas S, Rich A. Changing genetic information through RNA editing.

Identification of nitric oxide synthase as a protective locus against tuberculosis. Nitric oxide and macrophage function. Effects of the route of infection on immunoglobulin G subclasses and specificity of the reovirus-specific humoral immune response. Marie I, Hovanessian A G. The kDa A synthetase is composed of two homologous and adjacent functional domains. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor Differential expression and distinct structure of and kDa forms of A synthetase in human cells treated with interferon.

Inhibition of influenza C viruses by human MxA protein. Virus Res. Mason D, Powrie F. Control of immune pathology by regulatory T cells. Curr Opin Immunol. Neuronal nitric oxide synthase, a modular enzyme formed by convergent evolution: structure studies of a cysteine thiolate-liganded heme protein that hydroxylates L-arginine to produce NO as a cellular signal.

Mechanism of interferon action: inhibition of vesicular stomatitis virus replication in human amnion U cells by cloned human eukocyte interferon. Effect on viral macromolecular synthesis. Mathews M B. Mathews M B, Shenk T. Adenovirus virus-associated RNA and translational control. Inhibition of hepatitis B virus replication during schistosoma mansoni infection in transgenic mice. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C.

Hepatitis Interventional Therapy Group. Escape of human immunodeficiency virus from immune control. Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons. A mammalian RNA editing enzyme. Biochim Biophys Acta. The cellular inhibitor of the PKR protein kinase, P58 IPK , is an influenza virus-activated co-chaperone that modulates heat shockprotein 70 activity.

Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Tumor suppressor function of the interferon-induced double-stranded RNA-activated protein kinase. Constitutive expression of human double-stranded RNA-activated p68 kinase in murine cells mediates phosphorylation of eukaryotic initiation factor 2 and partial resistance to encephalomyocarditis virus growth.

Michel T, Feron O. Nitric oxide synthases: which, where, how, and why? Miller L K. Baculovirus interaction with host apoptotic pathways.

J Cell Physiol. The interferon-inducible p protein as a modulator of transcription: inhibition of NF-kappa B, c-Fos, and c-Jun activities. The type I interferon receptor: structure, function, and evolution of a family business. Monath T P. Dengue: the risk to developed and developing countries. Functional role of type I and type II interferons in antiviral defense. Biosynthesis of reovirus-specified polypeptides. Multiplication rate but not yield of reovirus serotypes 1 and 3 correlates with the level of virus-mediated inhibition of cellular protein synthesis.

Numerous transitions in human parainfluenza virus 3 RNA recovered from persistently infected cells. Nagano Y, Kojima Y. Inhibition de I'infection vaccinale par le virus homologue. Recent human influenza A H1N1 viruses are closely related genetically to strains isolated in Nathan C.

Inducible nitric oxide synthase: what difference does it make? The growing family of interferon regulatory factors. Cytokine Growth Factor Rev. Purification and properties of double-stranded RNA-specific adenosine deaminase from calf thymus.

Activation of the double-stranded-RNA-activated protein kinase and induction of vascular cell adhesion molecule-1 by poly I. Vesicular stomatitis virus defective interfering particles can contain extensive genome sequence rearrangements and base substitutions.

Oldstone M B A. How viruses escape from cytotoxic lymphocyes: molecular parameters and players. Jak2 is essential for signaling through a variety of cytokine receptors. Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase. PACT, a protein activator of the interferon-induced protein kinase. Role of the amino-terminal residues of the interferon-induced protein kinase in its activation by dsRNA and heparin.

Generation of a mutant form of protein synthesis initiation factor eIF-2 lacking the site of phosphorylation of eIF-2 kinases. Expression and regulation by interferon of a double-stranded RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mechanism of interferon action: double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons.

Enhanced virus resistance of transgenic mice expressing the human MxA protein. Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle. Evolution of the hepatitis C virus second envelope protein hypervariable region in chronically infected patients receiving alpha interferon therapy.

Interferon resistance of hepatitis C virus genotype 1b: relationship to nonstructural 5A gene quasispecies mutations. Interferons and their actions.

The A system: modulation of viral and cellular processes through acceleration of RNA degradation. Characterization of the effects of hepatitis C virus nonstructural 5A protein expression in human cell lines and on interferon-sensitive virus replication.

Dominant-negative mutants of human MxA protein: domains in the carboxy-terminal moiety are important for oligomerization and antiviral activity. Prejean C, Colamonici O R. Mice found either homozygous or heterozygous for the null mutation were matched for age 8 to 10 weeks , sex male , and levels of HBeAg in their serum before experimental manipulations. All animals were housed in pathogen-free rooms under strict barrier conditions. Louis, Mo.

Frozen liver tissue was mechanically pulverized under liquid nitrogen, and total genomic DNA and RNA were isolated exactly as previously described A two-tailed nonparametric Wilcoxon test was used to assess the statistical significance of the experimental variation in the intrahepatic content of HBV replicative forms among transgenic mice that were either heterozygous or homozygous for the IRF-1 or PKR null mutation.

HBV transgenic mice from lineage 1. As shown in Fig. The levels of HBV replication observed in all groups of heterozygous control mice were comparable to those observed in wild-type mice from lineage 1. The livers from the mice shown in Fig. As expected, neither message was detected in these uninflamed livers data not shown , and similar results were obtained for saline-injected controls from all lineages Fig. Six age 8 to 10 weeks -, sex male -, and serum HBeAg-matched mice that were either heterozygous or homozygous for the indicated null mutation were sacrificed, and the livers were harvested.

Bands corresponding to the integrated transgene Trans. The integrated transgene can be used to normalize the amount of DNA bound to the membrane. Bands corresponding to integrated transgene Trans. TNF, tumor necrosis factor; IL, interleukin. The results were compared with those observed for livers pooled from 10 age-, sex-, and serum HBeAg-matched transgenic littermates injected with saline NaCl.

The mean sALT activity, measured at the time of autopsy, is indicated for each group and is expressed in units per liter. Mice were bled and sacrificed, and livers were harvested 24 h later, when the antiviral activity of poly I-C is maximal 21 , Results were compared with those observed for livers pooled from six age-, sex-, and serum HBeAg-matched transgenic controls that were sacrificed 24 h after injection with saline.

The most significant reduction involved the single-stranded DNA forms, while the more mature, high-molecular-weight relaxed circular double-stranded DNA forms remained detectable, albeit at levels lower than those detected in control mice Fig. Under these circumstances, single-stranded DNA-containing capsids disappear after RNA-containing capsids but before mature capsids, which are cleared from hepatocytes with slower kinetics As also shown in Fig.

In keeping with the notion that poly I-C inhibits HBV replication noncytopathically 21 , little or no liver disease was observed either histologically data not shown or biochemically Fig.

Again, little or no liver disease was observed either histologically data not shown or biochemically Fig. Furthermore, it was recently shown that although EMCV is susceptible to the antiviral activity of either RNase L or PKR, the simultaneous disruption of both gene products is still associated with residual IFN-dependent antiviral activity 33 ; this result indicates that as-yet-undefined IFN-inducible antiviral pathways are operative in the control of EMCV.

Future research aimed at further defining IFN-induced intracellular molecular events that control HBV is clearly warranted. We thank Monte Hobbs for providing the cytokine gene probes used in the RPA experiments and Margie Chadwell for excellent technical assistance. This work was supported by grants AI to L. National Center for Biotechnology Information , U. Journal List J Virol v. J Virol.

Luca G. Silverman , 2 Bryan R. Williams , 2 and Francis V. Chisari 1. Robert H. Bryan R. Francis V. Author information Article notes Copyright and License information Disclaimer. Torrey Pines Rd. Phone: Fax: E-mail: ude. Received Oct 3; Accepted Dec 5. This article has been cited by other articles in PMC. Biochemical and histological analyses. Statistical analysis. Open in a separate window. TABLE 1. Acknowledgments We thank Monte Hobbs for providing the cytokine gene probes used in the RPA experiments and Margie Chadwell for excellent technical assistance.

Bachmaier, K. Neu, C. Pummerer, G. Duncan, T. Mak, T. Cebulla, C. Viral inhibition of interferon signal transduction. Intervirology 42 , — Goodbourn, S. Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. Garcia-Sastre, A. Microbes Infect. Isaacs, A. Virus interference. The interferon. B , — Haller, O. Mx proteins: mediators of innate resistance to RNA viruses. Bergmann, M. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems.

Inhibition of interferon-mediated antiviral responses by influenza A viruses and other negative-strand RNA viruses. Lee, T. The 58,dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase PKR is a member of the tetratricopeptide-repeat family of proteins.

Jr et al. Melville, M. The cellular inhibitor of the PKR protein kinase, P58 IPK , is an influenza virus-activated co-chaperone that modulates heat-shock protein 70 activity.

Polyak, S. The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity. Wang, X. Geiss, G. Cellular transcriptional profiling in influenza virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza.

This study examined the effects of NS1 protein expression during influenza A virus infection on global cellular mRNA levels using high-density microarrays. It indicated that the cellular IFN response to influenza A virus infection in lung epithelial cells is influenced markedly by the sequence of the NS1 gene, and it characterized a virus that contains the pandemic influenza NS1 gene. Krebs, D. SOCS proteins: negative regulators of cytokine signaling. Stem Cells 19 , — He, Y.

To interfere and to anti-interfere: the interplay between hepatitis C virus and interferon. Viral Immunol. Tan, S. How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A. Virology , 1—12 Taylor, D. Hepatitis C virus and interferon resistance: it's more than just PKR. Hepatology 33 , — Bartenschlager, R. Novel cell-culture systems for the hepatitis C virus.

Antiviral Res. Molecular clones of hepatitis C virus: applications to animal models. ILAR J. PubMed Article Google Scholar. Pawlotsky, J. Hepatitis C virus resistance to antiviral therapy.

Hepatology 32 , — Bukh, J. Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Liver Dis. Enomoto, N. Comparison of full-length sequences of interferon-sensitive and -resistant hepatitis C virus 1b. Sensitivity to interferon is conferred by amino-acid substitutions in the NS5A region.

Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. Nakano, I. Witherell, G.

Statistical analysis of combined substitutions in nonstructural 5A region of hepatitis C virus and interferon response. Lohmann, V. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science , — Blight, K. Frese, M. Guo, J. Sumpter, R. Whitley, R. USA 97 , — Roizman, B. Ankel, H.

Kumar-Sinha, C. Preston, C. Activation of interferon response factor-3 in human cells infected with herpes simplex virus type 1 or human cytomegalovirus. Eidson, K. Expression of herpes simplex virus ICP0 inhibits the induction of interferon-stimulated genes by viral infection. Mossman, K. Harle, P. Jr, Carr, D. He, B. USA 94 , — Cassady, K. The herpes simplex virus type 1 U S 11 protein interacts with protein kinase R in infected cells and requires a amino-acid sequence adjacent to a kinase substrate domain.

Leib, D. Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene. Using recombinant viruses to infect animals that have null mutations in host-defence genes, this study showed that a virus that was attenuated by deletion of ICP Poppers, J. Esposito, J. Moss, B. Cohen, J. Smallpox vaccinations: how much protection remains?

Science , Smith, G. Smallpox: anything to declare? Nature Rev. Alcami, A. Trends Microbiol. McFadden, G. Host-related immunomodulators encoded by poxviruses and herpesviruses. Lalani, A. Use of chemokine receptors by poxviruses.

Cytokine receptors encoded by poxviruses: a lesson in cytokine biology. Today 16 , — Virus-encoded receptors for cytokines and chemokines. Cell Dev.

Colamonici, O. Symons, J. Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity.

Cell 81 , — This study characterized the vaccinia-virus soluble type I IFN receptor encoded by the B18R gene, which has broad species specificity and might have aided vaccinia-virus replication in many host species during evolution.

Verardi, P. Sroller, V. Akkaraju, G. Vaccinia-specific kinase inhibitory factor prevents translational inhibition by double-stranded RNA in rabbit reticulocyte lysate.

Watson, J. Characterization of a vaccinia virus-encoded double-stranded RNA-binding protein that may be involved in inhibition of the double-stranded RNA-dependent protein kinase. Chang, H. The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. USA 89 , — Beattie, E. Davies, M. Massung, R. Analysis of the complete genome of smallpox variola major virus strain Bangladesh Shchelkunov, S. Comparison of the genetic maps of variola and vaccinia viruses.

FEBS Lett. The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms. Sharp, T. Carroll, K. Engagement of soluble resistance-related calcium binding protein sorcin with foot-and-mouth disease virus FMDV VP1 inhibits type I interferon response in cells.

Vet Microbiol , 35—46 Plos Pathog 8 10 , e The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities.

Virology , — Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. PNAS , — Nature , — Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection. J Immunol , — J Virol 85 , — Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor.

Plos Pathog 7 3 , e Plos Pathog 9 , e J Virol 77 , — J Virol 84 , — Emergence in Asia of foot-and-mouth disease viruses with altered host range: characterization of alterations in the 3A protein. J Virol 75 , — Interaction of foot-and-mouth disease virus nonstructural protein 3A with host protein DCTN3 is important for viral virulence in cattle. Membrane topology and cellular dynamics of foot-and-mouth disease virus 3A protein. Plos one 9 , e Identification of a nucleotide deletion in parts of polypeptide 3A in two independent attenuated aphthovirus strains.

A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle. Glycogen synthase kinase 3beta regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1.

Immunity 33 , — Mol Cell 19 , — EMBO J 24 , — Nat Immunol 10 , — Performance of a foot-and-mouth disease virus reverse transcription-polymerase chain reaction with amplification controls between three real-time instruments. J Vet Diagn Invest 19 , 9—20 Support Center Support Center. External link. Please review our privacy policy. Amplification of 3A aa 1— Amplification of 3A aa 52— Amplification of 3A aa — Q-PCR for detection of human ifnb gene.

Q-PCR for detection of human cxcl10 gene. Q-PCR for detection of human isg56 gene. Q-PCR for detection of human rantes gene. Q-PCR for detection of human rig-i gene.