Interferon signalling network in innate defence

Interferons (IFNs) elicit multifaceted effects in host innate defence. Accumulating evidence revealed that not only the first identified Jak‐Stat pathway but also other newly found signalling pathways are required for the induction of versatile responses by IFNs. In particular, type I IFNs are inducible by viral infection through the recognition of pathogen‐associated molecules by pattern recognition receptors, and the induction of multiple IFN‐stimulated genes through the activation of type I IFN signalling confers antiviral and immunomodulatory activities. Any step in this process is often targeted by viruses for their immuno‐evasion. The regulatory function of constitutive IFN‐α/β signalling has been recognized in terms of its boosting effect on cellular responsiveness in host defence systems. Further comprehensive understanding of IFN signalling may offer a better direction to unravelling the complex signalling networks in the host defence system, and may contribute to their more effective therapeutic applications.

[1]  B. Beutler,et al.  TYPE I INTERFERONS (/) IN IMMUNITY AND AUTOIMMUNITY , 2005 .

[2]  B. Zhivotovsky,et al.  Interferon (cid:1) -induced Apoptosis in Tumor Cells Is Mediated through the Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Signaling Pathway* , 2022 .

[3]  E. Fish,et al.  Diversity and relatedness among the type I interferons. , 2004, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[4]  J. Darnell,et al.  Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene , 1991, Molecular and cellular biology.

[5]  G. Lutfalla,et al.  Genetic transfer of a functional human interferon α receptor into mouse cells: Cloning and expression of its c-DNA , 1990, Cell.

[6]  L. Platanias,et al.  The Rac1/p38 mitogen-activated protein kinase pathway is required for interferon alpha-dependent transcriptional activation but not serine phosphorylation of Stat proteins. , 2000, The Journal of biological chemistry.

[7]  S. Akira,et al.  Toll-like receptors in innate immunity. , 2004, International immunology.

[8]  T. Taniguchi,et al.  CD8 (+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-α/β signaling , 2000 .

[9]  I. Gresser.  Biologic effects of interferons. , 1990, The Journal of investigative dermatology.

[10]  X. Mo,et al.  Host response to Sendai virus in mice lacking class II major histocompatibility complex glycoproteins , 1995, Journal of virology.

[11]  R. Buller,et al.  Induction of cytotoxic T-cell responses in vivo in the absence of CD4 helper cells , 1987, Nature.

[12]  Stanley M Lemon,et al.  Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  T. Taniguchi,et al.  Cross talk of the interferon‐α/β signalling complex with gp130 for effective interleukin‐6 signalling , 2001 .

[14]  B. Williams,et al.  Identification and characterization of an interferon (IFN)-stimulated response element-IFN-stimulated gene factor 3-independent signaling pathway for IFN-alpha. , 1994, The Journal of biological chemistry.

[15]  B. Williams,et al.  Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays , 1998 .

[16]  H. S. Warren,et al.  Toll-like receptors. , 2005, Critical care medicine.

[17]  D. Levy,et al.  The virus battles: IFN induction of the antiviral state and mechanisms of viral evasion. , 2001, Cytokine & growth factor reviews.

[18]  T. Taniguchi,et al.  Positive feedback regulation of type I IFN genes by the IFN‐inducible transcription factor IRF‐7 , 1998, FEBS letters.

[19]  T. Taniguchi,et al.  IRF family of transcription factors as regulators of host defense. , 2001, Annual review of immunology.

[20]  J. Farrar,et al.  Frontline: Absence of functional STAT4 activation despite detectable tyrosine phosphorylation induced by murine IFN‐α , 2004, European journal of immunology.

[21]  T. Taniguchi,et al.  New aspects of IFN‐α/β signalling in immunity, oncogenesis and bone metabolism , 2003 .

[22]  M. Esteban,et al.  Interferon treatment inhibits early events in vaccinia virus gene expression in infected mice. , 1991, Virology.

[23]  D. Levy,et al.  ISGF3 gamma p48, a specificity switch for interferon activated transcription factors. , 1996, Cytokine & growth factor reviews.

[24]  G. Stark,et al.  A protein tyrosine kinase in the interferon alpha/beta signaling pathway. , 1992, Cell.

[25]  A. Alcamí,et al.  Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species soecificity , 1995, Cell.

[26]  H. W. Chang,et al.  The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Michael G. Katze,et al.  Viruses and interferon: a fight for supremacy , 2002, Nature Reviews Immunology.

[28]  A. Bowie,et al.  A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[29]  T. Taniguchi,et al.  Distinct and Essential Roles of Transcription Factors IRF-3 and IRF-7 in Response to Viruses for IFN-α/β Gene Induction , 2000 .

[30]  J. Gugenheim,et al.  Interferon messenger RNA is produced constitutively in the organs of normal individuals. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[31]  K. Honda,et al.  Negative regulation of IFN-alpha/beta signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  G. Karupiah,et al.  Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication , 1995, Journal of virology.

[33]  S. Kotenko,et al.  The Class II cytokine receptor (CRF2) family: overview and patterns of receptor-ligand interactions. , 2004, Cytokine & growth factor reviews.

[34]  C. D. Krause,et al.  Interferons, interferon‐like cytokines, and their receptors , 2004, Immunological reviews.

[35]  R. Buller,et al.  Vaccinia Virus B18R Gene Encodes a Type I Interferon-binding Protein That Blocks Interferon α Transmembrane Signaling (*) , 1995, The Journal of Biological Chemistry.

[36]  B. Williams,et al.  Transcriptional regulation of interferon-stimulated genes. , 1991, European journal of biochemistry.

[37]  A. Alcamí,et al.  Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity , 1995, Journal of virology.

[38]  G. Stark,et al.  How cells respond to interferons. , 1998, Annual review of biochemistry.

[39]  T. Taniguchi,et al.  Requirement of the IFN‐α/β‐induced CXCR3 chemokine signalling for CD8+ T cell activation , 2002, Genes to cells : devoted to molecular & cellular mechanisms.

[40]  Ralf Bartenschlager,et al.  Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus , 2005, Nature.

[41]  S. Pestka.  The human interferon alpha species and receptors. , 2000, Biopolymers.

[42]  A. Alcamí,et al.  Analysis of an Interaction between the Soluble Vaccinia Virus-Coded Type I Interferon (IFN)-Receptor and Human IFN-α1 and IFN-α2 , 1997 .

[43]  E. Petricoin,et al.  Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins. , 1995, Science.

[44]  Polly Matzinger,et al.  A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell , 1998, Nature.

[45]  A. Verma,et al.  Protein Kinase C-δ (PKC-δ) Is Activated by Type I Interferons and Mediates Phosphorylation of Stat1 on Serine 727* , 2002, The Journal of Biological Chemistry.

[46]  A. García-Sastre.  Mechanisms of inhibition of the host interferon α/β-mediated antiviral responses by viruses , 2002 .

[47]  B. Williams,et al.  p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons , 1999, The EMBO journal.

[48]  J. Darnell,et al.  Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. , 1995, Annual review of biochemistry.

[49]  D. Lew.  Cytoplasmic activation ofGAF,an IFN-'y-regulated DNA-binding factor , 1991 .

[50]  Yong‐jun Liu,et al.  IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. , 2005, Annual review of immunology.

[51]  L. Platanias,et al.  Association of the Interferon- dependent Tyrosine Kinase Tyk-2 with the Hematopoietic Cell Phosphatase (*) , 1995, The Journal of Biological Chemistry.

[52]  R. Roberts,et al.  The Evolution of the Type I Interferons1 , 1998 .

[53]  William Lee,et al.  Chronic Hepatitis B Virus Infection: Treatment Strategies for the Next Millennium , 2000, Annals of Internal Medicine.

[54]  M. White,et al.  The Type I Interferon Receptor Mediates Tyrosine Phosphorylation of Insulin Receptor Substrate 2 (*) , 1996, The Journal of Biological Chemistry.

[55]  B. Williams,et al.  Identification and characterization of an interferon (IFN)-stimulated response element-IFN-stimulated gene factor 3-independent signaling pathway for IFN-α , 1994 .

[56]  J. Darnell,et al.  Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons , 1991, Molecular and cellular biology.

[57]  J. Darnell,et al.  Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. , 1994, Science.

[58]  L. Platanias,et al.  Activation of the p 38 Mitogen-activated Protein Kinase by Type I Interferons , 1999 .

[59]  S. Hida,et al.  Defective development of splenic and epidermal CD4+ dendritic cells in mice deficient for IFN regulatory factor-2. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[60]  R. Zinkernagel,et al.  Immune response in mice that lack the interferon-gamma receptor. , 1993, Science.

[61]  Shizuo Akira,et al.  Toll-like receptor signalling , 2004, Nature Reviews Immunology.

[62]  M. Gale,et al.  Evasion of intracellular host defence by hepatitis C virus , 2005, Nature.

[63]  L. Platanias,et al.  Activation of a CrkL-Stat5 Signaling Complex by Type I Interferons* , 1999, The Journal of Biological Chemistry.

[64]  T. Kasahara,et al.  [Interleukin-1 receptor]. , 1997, Nihon rinsho. Japanese journal of clinical medicine.

[65]  Y. Matsuzawa,et al.  Limitin: An interferon-like cytokine that preferentially influences B-lymphocyte precursors , 2000, Nature Medicine.

[66]  I. Kerr,et al.  Jaks and Stats in signaling by the cytokine receptor superfamily. , 1995, Trends in genetics : TIG.

[67]  C. Coban,et al.  Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction , 2005, The Journal of experimental medicine.

[68]  S. Harroch,et al.  Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN‐alpha and IFN‐beta. , 1994, The EMBO journal.

[69]  K. Honda,et al.  Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[70]  A. Alcamí,et al.  Receptors for gamma-interferon encoded by poxviruses: implications for the unknown origin of vaccinia virus. , 1996, Trends in microbiology.

[71]  I. Kerr,et al.  Differential responses to IFN-alpha subtypes in human T cells and dendritic cells. , 2003, Journal of immunology.

[72]  J. Darnell,et al.  Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. , 1992, Science.

[73]  O. Elroy-Stein,et al.  The vaccinia virus K3L gene product potentiates translation by inhibiting double-stranded-RNA-activated protein kinase and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 , 1992, Journal of virology.

[74]  M. Esteban,et al.  Interferon-γ Severely Inhibits DNA Synthesis of Vaccinia Virus in a Macrophage Cell Line , 1994 .

[75]  Hideo Negishi,et al.  IRF-7 is the master regulator of type-I interferon-dependent immune responses , 2005, Nature.

[76]  M. Esteban,et al.  Interferon-gamma severely inhibits DNA synthesis of vaccinia virus in a macrophage cell line. , 1994, Virology.

[77]  Kozo Nakamura,et al.  RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β , 2002, Nature.

[78]  I. Kerr,et al.  Janus Kinase-dependent Activation of Insulin Receptor Substrate 1 in Response to Interleukin-4, Oncostatin M, and the Interferons* , 1997, The Journal of Biological Chemistry.

[79]  D. Levy,et al.  ISGF3γ p48, a specificity switch for interferon activated transcription factors , 1996 .

[80]  T. Taniguchi,et al.  A weak signal for strong responses: interferon-alpha/beta revisited , 2001, Nature Reviews Molecular Cell Biology.

[81]  J. Hoofnagle,et al.  Pathogenesis, Natural History, Treatment, and Prevention of Hepatitis C , 2000, Annals of Internal Medicine.

[82]  J. Vilček.  Novel interferons , 2003, Nature Immunology.

[83]  R. Roberts,et al.  Current TopicTrophoblast Interferons , 1999 .

[84]  M. Biffi,et al.  References Subscriptions Permissions Email Alerts The Role of Stat4 in Species-Specific Regulation of Th Cell Development by Type I , 2013 .

[85]  Z. Zhai,et al.  VISA is an adapter protein required for virus-triggered IFN-beta signaling. , 2005, Molecular cell.

[86]  M Aguet,et al.  The IFN gamma receptor: a paradigm for cytokine receptor signaling. , 1997, Annual review of immunology.

[87]  K. Honda,et al.  Spatiotemporal regulation of MyD88–IRF-7 signalling for robust type-I interferon induction , 2005, Nature.

[88]  F. Belardelli,et al.  The essential role of endogenous IFN α/β in the anti‐metastatic action of sensitized T lymphocytes in mice injected with friend erythroleukemia cells , 1995 .

[89]  M. White,et al.  Interferon-α Engages the Insulin Receptor Substrate-1 to Associate with the Phosphatidylinositol 3′-Kinase (*) , 1995, The Journal of Biological Chemistry.

[90]  D. Levy,et al.  Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. , 1990, Genes & development.

[91]  S. Akira,et al.  TLR signaling. , 2006, Current topics in microbiology and immunology.

[92]  Scott R. Presnell,et al.  IL-28, IL-29 and their class II cytokine receptor IL-28R , 2002, Nature Immunology.

[93]  C. Horvath.  Silencing STATs: lessons from paramyxovirus interferon evasion. , 2004, Cytokine & growth factor reviews.

[94]  T. Decker,et al.  Cytoplasmic activation of GAF, an IFN‐gamma‐regulated DNA‐binding factor. , 1991, The EMBO journal.

[95]  D. Lejeune,et al.  Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3. , 2003, The Biochemical journal.

[96]  Hiroaki Ikeda,et al.  The roles of IFN gamma in protection against tumor development and cancer immunoediting. , 2002, Cytokine & growth factor reviews.

[97]  S. Pestka,et al.  Other Kinases Can Substitute for Jak2 in Signal Transduction by Interferon-γ* , 1996, The Journal of Biological Chemistry.

[98]  B. Williams,et al.  Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[99]  Amit Verma,et al.  The p38 MAPK Pathway Mediates the Growth Inhibitory Effects of Interferon-α in BCR-ABL-expressing Cells* , 2001, The Journal of Biological Chemistry.

[100]  T. Taniguchi.  Cytokine signaling through nonreceptor protein tyrosine kinases. , 1995, Science.

[101]  M. Gale,et al.  CARD games between virus and host get a new player. , 2006, Trends in immunology.

[102]  T. Taniguchi,et al.  The interferon-α/β system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors , 2002 .

[103]  L. Pfeffer,et al.  Interferon α/β Promotes Cell Survival by Activating Nuclear Factor κB through Phosphatidylinositol 3-Kinase and Akt* , 2001, The Journal of Biological Chemistry.

[104]  Z. Zhai,et al.  VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling , 2005 .

[105]  D. Levy,et al.  Differential viral induction of distinct interferon‐α genes by positive feedback through interferon regulatory factor‐7 , 1998, The EMBO journal.

[106]  R. Roberts,et al.  Trophoblast interferons. , 1999, Placenta.

[107]  Osamu Takeuchi,et al.  IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction , 2005, Nature Immunology.

[108]  G. Karupiah,et al.  Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. , 1993, Science.

[109]  G. Karupiah,et al.  Importance of interferons in recovery from mousepox , 1993, Journal of virology.

[110]  I. Kerr,et al.  Differential Responses to IFN-α Subtypes in Human T Cells and Dendritic Cells 12 , 2003, The Journal of Immunology.

[111]  T. Taniguchi,et al.  Cross talk between interferon-gamma and -alpha/beta signaling components in caveolar membrane domains. , 2000, Science.

[112]  M. Brunda,et al.  Interferons and Other Cytokines , 1997 .

[113]  S. Pestka,et al.  A species of human alpha interferon that lacks the ability to boost human natural killer activity. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[114]  Zhijian J. Chen,et al.  Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. , 2005, Cell.

[115]  G. Kochs,et al.  Inverse interference: how viruses fight the interferon system. , 2004, Viral immunology.

[116]  J. Lord,et al.  Inhibition of Neutrophil Apoptosis by Type 1 IFN Depends on Cross-Talk Between Phosphoinositol 3-Kinase, Protein Kinase C-δ, and NF-κB Signaling Pathways1 , 2003, The Journal of Immunology.

[117]  M. Rubinstein,et al.  The interferon receptors. , 1986, CRC critical reviews in biochemistry.

[118]  M. Kohonen-Corish,et al.  Immunodeficient mice recover from infection with vaccinia virus expressing interferon‐γ , 1990, European journal of immunology.

[119]  A. García-Sastre.  Mechanisms of inhibition of the host interferon alpha/beta-mediated antiviral responses by viruses. , 2002, Microbes and infection.

[120]  B. Cohen,et al.  The human interferon alpha/beta receptor: characterization and molecular cloning. , 1994, Cell.

[121]  Shizuo Akira,et al.  The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses , 2004, Nature Immunology.

[122]  G. Stark,et al.  Roles of Phosphatidylinositol 3-Kinase in Interferon-γ-dependent Phosphorylation of STAT1 on Serine 727 and Activation of Gene Expression* , 2001, The Journal of Biological Chemistry.

[123]  L. Pfeffer,et al.  STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor. , 1997, Science.

[124]  K. Murphy,et al.  Issues in T‐helper 1 development – resolved and unresolved , 2004, Immunological reviews.

[125]  I. Haga,et al.  Vaccinia virus protein A46R targets multiple Toll-like–interleukin-1 receptor adaptors and contributes to virulence , 2005, The Journal of experimental medicine.

[126]  C. Biron,et al.  Natural killer cells in antiviral defense: function and regulation by innate cytokines. , 1999, Annual review of immunology.

[127]  T. Taniguchi,et al.  Constitutive IFN-a/ Signal for Efficient IFN-a/ Gene Induction by Virus , 2001 .

[128]  S. Baron,et al.  The interferons. Mechanisms of action and clinical applications. , 1991, JAMA.

[129]  P. Moore,et al.  Interferon-κ, a Novel Type I Interferon Expressed in Human Keratinocytes* , 2001, The Journal of Biological Chemistry.

[130]  Lloyd J. Old,et al.  The roles of IFNγ in protection against tumor development and cancer immunoediting , 2002 .

[131]  B. Williams,et al.  Signal transduction in the interferon system. , 1998, Seminars in oncology.

[132]  C. Schindler,et al.  Dysregulated Sonic hedgehog signaling and medulloblastoma consequent to IFN-α–stimulated STAT2-independent production of IFN-γ in the brain , 2003 .

[133]  M. Woodruff,et al.  Immune Response , 1969, Nature.

[134]  G. Lutfalla,et al.  Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA. , 1990, Cell.

[135]  K C Zoon,et al.  Interferons and their actions. , 1987, Annual review of biochemistry.

[136]  P. Heinrich,et al.  Principles of interleukin (IL)-6-type cytokine signalling and its regulation. , 2003, The Biochemical journal.

[137]  S. Goodbourn,et al.  The V Protein of Simian Virus 5 Inhibits Interferon Signalling by Targeting STAT1 for Proteasome-Mediated Degradation , 1999, Journal of Virology.

[138]  M. Katze,et al.  To interfere and to anti-interfere: the interplay between hepatitis C virus and interferon. , 2002, Viral immunology.

[139]  R. Roberts,et al.  The evolution of the type I interferons. , 1998, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[140]  R. Schreiber,et al.  A critical function for type I interferons in cancer immunoediting , 2005, Nature Immunology.

[141]  S. Taki.  Type I interferons and autoimmunity: lessons from the clinic and from IRF-2-deficient mice. , 2002, Cytokine & growth factor reviews.

[142]  Hideo Negishi,et al.  Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence , 2003, Nature.

[143]  L. Platanias,et al.  Interferon-dependent activation of the serine kinase PI 3'-kinase requires engagement of the IRS pathway but not the Stat pathway. , 2000, Biochemical and biophysical research communications.

[144]  Zhijian J. Chen,et al.  Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3 , 2005, Cell.

[145]  S. Akira,et al.  The RNA Helicase Lgp2 Inhibits TLR-Independent Sensing of Viral Replication by Retinoic Acid-Inducible Gene-I1 , 2005, The Journal of Immunology.

[146]  J. Prieto,et al.  Interferon beta promotes survival in primary astrocytes through phosphatidylinositol 3-kinase , 2003, Journal of Neuroimmunology.

[147]  S. Goodbourn,et al.  The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[148]  L. Pfeffer,et al.  Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt. , 2001, The Journal of biological chemistry.

[149]  K. Honda,et al.  Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells , 2004 .

[150]  Shizuo Akira,et al.  Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity1 , 2005, The Journal of Immunology.

[151]  E. Demaeyer,et al.  Interferons and other regulatory cytokines , 1988 .

[152]  D. Levy,et al.  Interferon-induced nuclear signalling by Jak protein tyrosine kinases , 1993, Nature.

[153]  B. Beutler,et al.  Type I interferons (alpha/beta) in immunity and autoimmunity. , 2005, Annual review of immunology.

[154]  D. Haig.  Poxvirus interference with the host cytokine response. , 1998, Veterinary immunology and immunopathology.

[155]  S. Goodbourn,et al.  Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. , 2000, The Journal of general virology.

[156]  C. Coban,et al.  Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6 , 2004, Nature Immunology.

[157]  M Aguet,et al.  Functional role of type I and type II interferons in antiviral defense. , 1994, Science.

[158]  V. Bocci.  The physiological interferon response. , 1985, Immunology today.

[159]  A. Alcamí,et al.  Soluble interferon-gamma receptors encoded by poxviruses. , 1996, Comparative immunology, microbiology and infectious diseases.

[160]  M. Guillomot,et al.  Interferon-delta: the first member of a novel type I interferon family. , 1998, Biochimie.

[161]  L. Pfeffer,et al.  STAT3 complements defects in an interferon-resistant cell line: evidence for an essential role for STAT3 in interferon signaling and biological activities. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[162]  I. Haga,et al.  Evasion of innate immunity by vaccinia virus , 2005, Parasitology.

[163]  T. Taniguchi,et al.  Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development , 1993, Cell.

[164]  C Upton,et al.  Encoding of a homolog of the IFN-gamma receptor by myxoma virus. , 1992, Science.

[165]  M. White,et al.  Interferon-alpha engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3'-kinase. , 1995, The Journal of biological chemistry.

[166]  J. Ihle.  The Janus protein tyrosine kinases in hematopoietic cytokine signaling. , 1995, Seminars in immunology.

[167]  G. Karupiah,et al.  Interferon gamma is involved in the recovery of athymic nude mice from recombinant vaccinia virus/interleukin 2 infection , 1990, The Journal of experimental medicine.

[168]  A. Lewis-Antes,et al.  IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. , 2003, Nature immunology.

[169]  A. Alcamí,et al.  Soluble interferon-γ receptors encoded by poxviruses , 1996 .