1932

Abstract

The interferon system protects mammals against virus infections. There are several types of interferons, which are characterized by their ability to inhibit virus replication and resultant pathogenesis by triggering both innate and cell-mediated immune responses. Virus infection is sensed by a variety of cellular pattern-recognition receptors and triggers the synthesis of interferons, which are secreted by the infected cells. In uninfected cells, cell surface receptors recognize the secreted interferons and activate intracellular signaling pathways that induce the expression of interferon-stimulated genes; the proteins encoded by these genes inhibit different stages of virus replication. To avoid extinction, almost all viruses have evolved mechanisms to defend themselves against the interferon system. Consequently, a dynamic equilibrium of survival is established between the virus and its host, an equilibrium that can be shifted to the host's favor by the use of exogenous interferon as a therapeutic antiviral agent.

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2015-11-09
2024-10-04
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Literature Cited

  1. Isaacs A, Lindenmann J. 1.  1957. Virus interference. I. The interferon. Proc. R. Soc. B 147:258–67 [Google Scholar]
  2. Schneider WM, Chevillotte MD, Rice CM. 2.  2014. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol. 32:513–45 [Google Scholar]
  3. Versteeg GA, Garcia-Sastre A. 3.  2010. Viral tricks to grid-lock the type I interferon system. Curr. Opin. Microbiol. 13:508–16 [Google Scholar]
  4. McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. 4.  2015. Type I interferons in infectious disease. Nat. Rev. Immunol. 15:87–103 [Google Scholar]
  5. de Weerd NA, Nguyen T. 5.  2012. The interferons and their receptors—distribution and regulation. Immunol. Cell Biol. 90:483–91 [Google Scholar]
  6. O'Brien TR, Prokunina-Olsson L, Donnelly RP. 6.  2014. IFN-λ4: the paradoxical new member of the interferon lambda family. J. Interferon Cytokine Res. 34:829–38 [Google Scholar]
  7. Pestka S, Krause CD, Walter MR. 7.  2004. Interferons, interferon-like cytokines, and their receptors. Immunol. Rev. 202:8–32 [Google Scholar]
  8. Fitzgerald-Bocarsly P, Dai J, Singh S. 8.  2008. Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history. Cytokine Growth Factor Rev. 19:3–19 [Google Scholar]
  9. Fung KY, Mangan NE, Cumming H, Horvat JC, Mayall JR. 9.  et al. 2013. Interferon-ε protects the female reproductive tract from viral and bacterial infection. Science 339:1088–92 [Google Scholar]
  10. Hardy MP, Owczarek CM, Jermiin LS, Ejdeback M, Hertzog PJ. 10.  2004. Characterization of the type I interferon locus and identification of novel genes. Genomics 84:331–45 [Google Scholar]
  11. Mordstein M, Neugebauer E, Ditt V, Jessen B, Rieger T. 11.  et al. 2010. Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. J. Virol. 84:5670–77 [Google Scholar]
  12. Sheahan T, Imanaka N, Marukian S, Dorner M, Liu P. 12.  et al. 2014. Interferon lambda alleles predict innate antiviral immune responses and hepatitis C virus permissiveness. Cell Host Microbe 15:190–202 [Google Scholar]
  13. Sommereyns C, Paul S, Staeheli P, Michiels T. 13.  2008. IFN-lambda (IFN-λ) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLOS Pathog. 4e1000017 [Google Scholar]
  14. Der SD, Zhou A, Williams BR, Silverman RH. 14.  1998. Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays. PNAS 95:15623–28 [Google Scholar]
  15. Doyle SE, Schreckhise H, Khuu-Duong K, Henderson K, Rosler R. 15.  et al. 2006. Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes. Hepatology 44:896–906 [Google Scholar]
  16. Decker T, Kovarik P, Meinke A. 16.  1997. GAS elements: a few nucleotides with a major impact on cytokine-induced gene expression. J. Interferon Cytokine Res. 17:121–34 [Google Scholar]
  17. Platanias LC. 17.  2005. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 5:375–86 [Google Scholar]
  18. Pestka S. 18.  2007. The interferons: 50 years after their discovery, there is much more to learn. J. Biol. Chem. 282:20047–51 [Google Scholar]
  19. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M. 19.  et al. 2003. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat. Immunol. 4:69–77 [Google Scholar]
  20. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S. 20.  et al. 2003. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat. Immunol. 4:63–68 [Google Scholar]
  21. Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H. 21.  et al. 2013. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat. Genet. 45:164–71 [Google Scholar]
  22. Key FM, Peter B, Dennis MY, Huerta-Sanchez E, Tang W. 22.  et al. 2014. Selection on a variant associated with improved viral clearance drives local, adaptive pseudogenization of interferon lambda 4 (IFNL4). PLOS Genet. 10:e1004681 [Google Scholar]
  23. Pandey S, Kawai T, Akira S. 23.  2015. Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors. Cold Spring Harb. Perspect. Biol. 7:a016246 [Google Scholar]
  24. Gay NJ, Symmons MF, Gangloff M, Bryant CE. 24.  2014. Assembly and localization of Toll-like receptor signalling complexes. Nat. Rev. Immunol. 14:546–58 [Google Scholar]
  25. Yoneyama M, Onomoto K, Jogi M, Akaboshi T, Fujita T. 25.  2015. Viral RNA detection by RIG-I-like receptors. Curr. Opin. Immunol. 32:48–53 [Google Scholar]
  26. Wu J, Chen ZJ. 26.  2014. Innate immune sensing and signaling of cytosolic nucleic acids. Annu. Rev. Immunol. 32:461–88 [Google Scholar]
  27. Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA. 27.  et al. 2001. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194:863–69 [Google Scholar]
  28. Zarember KA, Godowski PJ. 28.  2002. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J. Immunol. 168:554–61 [Google Scholar]
  29. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. 29.  2001. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413:732–38 [Google Scholar]
  30. Hardarson HS, Baker JS, Yang Z, Purevjav E, Huang CH. 30.  et al. 2007. Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury. Am. J. Physiol. Heart Circ. Physiol. 292:H251–58 [Google Scholar]
  31. Le Goffic R, Balloy V, Lagranderie M, Alexopoulou L, Escriou N. 31.  et al. 2006. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLOS Pathog. 2e53 [Google Scholar]
  32. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G. 32.  et al. 2007. TLR3 deficiency in patients with herpes simplex encephalitis. Science 317:1522–27 [Google Scholar]
  33. Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A. 33.  2007. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315:1398–401 [Google Scholar]
  34. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M. 34.  et al. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–5 [Google Scholar]
  35. Gitlin L, Barchet W, Gilfillan S, Cella M, Beutler B. 35.  et al. 2006. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. PNAS 103:8459–64 [Google Scholar]
  36. Goubau D, Schlee M, Deddouche S, Pruijssers AJ, Zillinger T. 36.  et al. 2014. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5′-diphosphates. Nature 514:372–75 [Google Scholar]
  37. Weber M, Gawanbacht A, Habjan M, Rang A, Borner C. 37.  et al. 2013. Incoming RNA virus nucleocapsids containing a 5′-triphosphorylated genome activate RIG-I and antiviral signaling. Cell Host Microbe 13:336–46 [Google Scholar]
  38. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T. 38.  et al. 2008. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J. Exp. Med. 205:1601–10 [Google Scholar]
  39. Zust R, Cervantes-Barragan L, Habjan M, Maier R, Neuman BW. 39.  et al. 2011. Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat. Immunol. 12:137–43 [Google Scholar]
  40. Bruns AM, Leser GP, Lamb RA, Horvath CM. 40.  2014. The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly. Mol. Cell 55:771–81 [Google Scholar]
  41. Childs KS, Randall RE, Goodbourn S. 41.  2013. LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA. PLOS ONE 8:e64202 [Google Scholar]
  42. Saito T, Hirai R, Loo YM, Owen D, Johnson CL. 42.  et al. 2007. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. PNAS 104:582–87 [Google Scholar]
  43. Krug A, French AR, Barchet W, Fischer JA, Dzionek A. 43.  et al. 2004. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 21:107–19 [Google Scholar]
  44. Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. 44.  2009. RIG-I-dependent sensing of poly (dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat. Immunol. 10:1065–72 [Google Scholar]
  45. Chiu YH, Macmillan JB, Chen ZJ. 45.  2009. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell 138:576–91 [Google Scholar]
  46. Unterholzner L. 46.  2013. The interferon response to intracellular DNA: Why so many receptors?. Immunobiology 218:1312–21 [Google Scholar]
  47. Chattopadhyay S, Sen GC. 47.  2014. Tyrosine phosphorylation in Toll-like receptor signaling. Cytokine Growth Factor Rev. 25:533–41 [Google Scholar]
  48. Sarkar SN, Elco CP, Peters KL, Chattopadhyay S, Sen GC. 48.  2007. Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-κB activation. J. Biol. Chem. 282:3423–27 [Google Scholar]
  49. Sarkar SN, Peters KL, Elco CP, Sakamoto S, Pal S, Sen GC. 49.  2004. Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat. Struct. Mol. Biol. 11:1060–67 [Google Scholar]
  50. Sarkar SN, Smith HL, Rowe TM, Sen GC. 50.  2003. Double-stranded RNA signaling by Toll-like receptor 3 requires specific tyrosine residues in its cytoplasmic domain. J. Biol. Chem. 278:4393–96 [Google Scholar]
  51. Liu L, Botos I, Wang Y, Leonard JN, Shiloach J. 51.  et al. 2008. Structural basis of Toll-like receptor 3 signaling with double-stranded RNA. Science 320:379–81 [Google Scholar]
  52. Yamashita M, Chattopadhyay S, Fensterl V, Saikia P, Wetzel JL, Sen GC. 52.  2012. Epidermal growth factor receptor is essential for Toll-like receptor 3 signaling. Sci. Signal. 5:ra50 [Google Scholar]
  53. Gack MU. 53.  2014. Mechanisms of RIG-I-like receptor activation and manipulation by viral pathogens. J. Virol. 88:5213–16 [Google Scholar]
  54. Maharaj NP, Wies E, Stoll A, Gack MU. 54.  2012. Conventional protein kinase C-α (PKC-α) and PKC-β negatively regulate RIG-I antiviral signal transduction. J. Virol. 86:1358–71 [Google Scholar]
  55. Wies E, Wang MK, Maharaj NP, Chen K, Zhou S. 55.  et al. 2013. Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling. Immunity 38:437–49 [Google Scholar]
  56. Gack MU, Shin YC, Joo CH, Urano T, Liang C. 56.  et al. 2007. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446:916–20 [Google Scholar]
  57. Zeng W, Sun L, Jiang X, Chen X, Hou F. 57.  et al. 2010. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141:315–30 [Google Scholar]
  58. Cai X, Chiu YH, Chen ZJ. 58.  2014. The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. Mol. Cell 54:289–96 [Google Scholar]
  59. Ford E, Thanos D. 59.  2010. The transcriptional code of human IFN-β gene expression. Biochim. Biophys. Acta 1799:328–36 [Google Scholar]
  60. Panne D, Maniatis T, Harrison SC. 60.  2007. An atomic model of the interferon-β enhanceosome. Cell 129:1111–23 [Google Scholar]
  61. Genin P, Vaccaro A, Civas A. 61.  2009. The role of differential expression of human interferon-A genes in antiviral immunity. Cytokine Growth Factor Rev. 20:283–95 [Google Scholar]
  62. Iversen MB, Paludan SR. 62.  2010. Mechanisms of type III interferon expression. J. Interferon Cytokine Res. 30:573–78 [Google Scholar]
  63. Onoguchi K, Yoneyama M, Takemura A, Akira S, Taniguchi T. 63.  et al. 2007. Viral infections activate types I and III interferon genes through a common mechanism. J. Biol. Chem. 282:7576–81 [Google Scholar]
  64. Osterlund PI, Pietila TE, Veckman V, Kotenko SV, Julkunen I. 64.  2007. IFN regulatory factor family members differentially regulate the expression of type III IFN (IFN-λ) genes. J. Immunol. 179:3434–42 [Google Scholar]
  65. Broz P, Monack DM. 65.  2013. Newly described pattern recognition receptors team up against intracellular pathogens. Nat. Rev. Immunol. 13:551–65 [Google Scholar]
  66. Andersen J, VanScoy S, Cheng TF, Gomez D, Reich NC. 66.  2008. IRF-3-dependent and augmented target genes during viral infection. Genes Immun. 9:168–75 [Google Scholar]
  67. Freaney JE, Kim R, Mandhana R, Horvath CM. 67.  2013. Extensive cooperation of immune master regulators IRF3 and NFκB in RNA Pol II recruitment and pause release in human innate antiviral transcription. Cell Rep. 4:959–73 [Google Scholar]
  68. Chattopadhyay S, Marques JT, Yamashita M, Peters KL, Smith K. 68.  et al. 2010. Viral apoptosis is induced by IRF-3-mediated activation of Bax. EMBO J. 29:1762–73 [Google Scholar]
  69. White CL, Chattopadhyay S, Sen GC. 69.  2011. Phosphatidylinositol 3-kinase signaling delays Sendai virus-induced apoptosis by preventing XIAP degradation. J. Virol. 85:5224–27 [Google Scholar]
  70. Chattopadhyay S, Fensterl V, Zhang Y, Veleeparambil M, Yamashita M, Sen GC. 70.  2013. Role of interferon regulatory factor 3-mediated apoptosis in the establishment and maintenance of persistent infection by Sendai virus. J. Virol. 87:16–24 [Google Scholar]
  71. Chattopadhyay S, Yamashita M, Zhang Y, Sen GC. 71.  2011. The IRF-3/Bax-mediated apoptotic pathway, activated by viral cytoplasmic RNA and DNA, inhibits virus replication. J. Virol. 85:3708–16 [Google Scholar]
  72. Ivashkiv LB, Donlin LT. 72.  2014. Regulation of type I interferon responses. Nat. Rev. Immunol. 14:36–49 [Google Scholar]
  73. Schroder K, Hertzog PJ, Ravasi T, Hume DA. 73.  2004. Interferon-γ: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75:163–89 [Google Scholar]
  74. Durbin RK, Kotenko SV, Durbin JE. 74.  2013. Interferon induction and function at the mucosal surface. Immunol. Rev. 255:25–39 [Google Scholar]
  75. Ng SL, Friedman BA, Schmid S, Gertz J, Myers RM. 75.  et al. 2011. IκB kinase ε (IKKε) regulates the balance between type I and type II interferon responses. PNAS 108:21170–75 [Google Scholar]
  76. Rajsbaum R, Versteeg GA, Schmid S, Maestre AM, Belicha-Villanueva A. 76.  et al. 2014. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response. Immunity 40:880–95 [Google Scholar]
  77. Stark GR. 77.  2007. How cells respond to interferons revisited: from early history to current complexity. Cytokine Growth Factor Rev. 18:419–23 [Google Scholar]
  78. Fish EN, Platanias LC. 78.  2014. Interferon receptor signaling in malignancy: a network of cellular pathways defining biological outcomes. Mol. Cancer Res. 12:1691–703 [Google Scholar]
  79. de Weerd NA, Vivian JP, Nguyen TK, Mangan NE, Gould JA. 79.  et al. 2013. Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1. Nat. Immunol. 14:901–7 [Google Scholar]
  80. de Weerd NA, Samarajiwa SA, Hertzog PJ. 80.  2007. Type I interferon receptors: biochemistry and biological functions. J. Biol. Chem. 282:20053–57 [Google Scholar]
  81. Samarajiwa SA, Mangan NE, Hardy MP, Najdovska M, Dubach D. 81.  et al. 2014. Soluble IFN receptor potentiates in vivo type I IFN signaling and exacerbates TLR4-mediated septic shock. J. Immunol. 192:4425–35 [Google Scholar]
  82. Gazziola C, Cordani N, Carta S, De Lorenzo E, Colombatti A, Perris R. 82.  2005. The relative endogenous expression levels of the IFNAR2 isoforms influence the cytostatic and pro-apoptotic effect of IFNα on pleomorphic sarcoma cells. Int. J. Oncol. 26:129–40 [Google Scholar]
  83. Malakhova OA, Kim KI, Luo JK, Zou W, Kumar KG. 83.  et al. 2006. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J. 25:2358–67 [Google Scholar]
  84. Piganis RA, de Weerd NA, Gould JA, Schindler CW, Mansell A. 84.  et al. 2011. Suppressor of cytokine signaling (SOCS) 1 inhibits type I interferon (IFN) signaling via the interferon α receptor (IFNAR1)-associated tyrosine kinase Tyk2. J. Biol. Chem. 286:33811–18 [Google Scholar]
  85. Cheon H, Holvey-Bates EG, Schoggins JW, Forster S, Hertzog P. 85.  et al. 2013. IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. EMBO J. 32:2751–63 [Google Scholar]
  86. Kroczynska B, Mehrotra S, Arslan AD, Kaur S, Platanias LC. 86.  2014. Regulation of interferon-dependent mRNA translation of target genes. J. Interferon Cytokine Res. 34:289–96 [Google Scholar]
  87. Mohr I, Sonenberg N. 87.  2012. Host translation at the nexus of infection and immunity. Cell Host Microbe 12:470–83 [Google Scholar]
  88. Kaur S, Lal L, Sassano A, Majchrzak-Kita B, Srikanth M. 88.  et al. 2007. Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signaling. J. Biol. Chem. 282:1757–68 [Google Scholar]
  89. Gonzalez-Navajas JM, Lee J, David M, Raz E. 89.  2012. Immunomodulatory functions of type I interferons. Nat. Rev. Immunol. 12:125–35 [Google Scholar]
  90. Schoggins JW. 90.  2014. Interferon-stimulated genes: roles in viral pathogenesis. Curr. Opin. Virol. 6:40–46 [Google Scholar]
  91. Karki S, Li MM, Schoggins JW, Tian S, Rice CM, MacDonald MR. 91.  2012. Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity. PLOS ONE 7:e37398 [Google Scholar]
  92. Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT. 92.  et al. 2011. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472:481–85 [Google Scholar]
  93. Schoggins JW, MacDuff DA, Imanaka N, Gainey MD, Shrestha B. 93.  et al. 2014. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature 505:691–95 [Google Scholar]
  94. Fensterl V, Wetzel JL, Ramachandran S, Ogino T, Stohlman SA. 94.  et al. 2012. Interferon-induced Ifit2/ISG54 protects mice from lethal VSV neuropathogenesis. PLOS Pathog. 8:e1002712 [Google Scholar]
  95. Bailey CC, Zhong G, Huang IC, Farzan M. 95.  2014. IFITM-family proteins: the cell's first line of antiviral defense. Annu. Rev. Virol. 1:261–83 [Google Scholar]
  96. Haller O, Staeheli P, Schwemmle M, Kochs G. 96.  2015. Mx GTPases: dynamin-like antiviral machines of innate immunity. Trends Microbiol. 23:154–63 [Google Scholar]
  97. Li J, Ding SC, Cho H, Chung BC, Gale M Jr.. 97.  2013. A short hairpin RNA screen of interferon-stimulated genes identifies a novel negative regulator of the cellular antiviral response. mBio 4:e00385–13 [Google Scholar]
  98. Liu SY, Sanchez DJ, Aliyari R, Lu S, Cheng G. 98.  2012. Systematic identification of type I and type II interferon-induced antiviral factors. PNAS 109:4239–44 [Google Scholar]
  99. Cho H, Shrestha B, Sen GC, Diamond MS. 99.  2013. A role for Ifit2 in restricting West Nile virus infection in the brain. J. Virol. 87:8363–71 [Google Scholar]
  100. Fensterl V, Wetzel JL, Sen GC. 100.  2014. Interferon-induced protein Ifit2 protects mice from infection of the peripheral nervous system by vesicular stomatitis virus. J. Virol. 88:10303–11 [Google Scholar]
  101. MacMicking JD. 101.  2012. Interferon-inducible effector mechanisms in cell-autonomous immunity. Nat. Rev. Immunol. 12:367–82 [Google Scholar]
  102. Sadler AJ, Williams BR. 102.  2008. Interferon-inducible antiviral effectors. Nat. Rev. Immunol. 8:559–68 [Google Scholar]
  103. Chakrabarti A, Jha BK, Silverman RH. 103.  2011. New insights into the role of RNase L in innate immunity. J. Interferon Cytokine Res. 31:49–57 [Google Scholar]
  104. Malathi K, Dong B, Gale M Jr, Silverman RH. 104.  2007. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448:816–19 [Google Scholar]
  105. Fensterl V, Sen GC. 105.  2011. The ISG56/IFIT1 gene family. J. Interferon Cytokine Res. 31:71–78 [Google Scholar]
  106. Fensterl V, Sen GC. 106.  2015. Interferon-induced Ifit proteins: their role in viral pathogenesis. J. Virol. 89:2462–68 [Google Scholar]
  107. Daffis S, Szretter KJ, Schriewer J, Li J, Youn S. 107.  et al. 2010. 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 468:452–56 [Google Scholar]
  108. Habjan M, Hubel P, Lacerda L, Benda C, Holze C. 108.  et al. 2013. Sequestration by IFIT1 impairs translation of 2′O-unmethylated capped RNA. PLOS Pathog. 9:e1003663 [Google Scholar]
  109. Kumar P, Sweeney TR, Skabkin MA, Skabkina OV, Hellen CU, Pestova TV. 109.  2014. Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5′-terminal regions of cap0-, cap1- and 5′ppp- mRNAs. Nucleic Acids Res. 42:3228–45 [Google Scholar]
  110. Pichlmair A, Lassnig C, Eberle CA, Gorna MW, Baumann CL. 110.  et al. 2011. IFIT1 is an antiviral protein that recognizes 5′-triphosphate RNA. Nat. Immunol. 12:624–30 [Google Scholar]
  111. Butchi NB, Hinton DR, Stohlman SA, Kapil P, Fensterl V. 111.  et al. 2014. Ifit2 deficiency results in uncontrolled neurotropic coronavirus replication and enhanced encephalitis via impaired alpha/beta interferon induction in macrophages. J. Virol. 88:1051–64 [Google Scholar]
  112. Blanc M, Hsieh WY, Robertson KA, Kropp KA, Forster T. 112.  et al. 2013. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38:106–18 [Google Scholar]
  113. Civra A, Cagno V, Donalisio M, Biasi F, Leonarduzzi G. 113.  et al. 2014. Inhibition of pathogenic non-enveloped viruses by 25-hydroxycholesterol and 27-hydroxycholesterol. Sci. Rep. 4:7487 [Google Scholar]
  114. Liu SY, Aliyari R, Chikere K, Li G, Marsden MD. 114.  et al. 2013. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38:92–105 [Google Scholar]
  115. Durfee LA, Lyon N, Seo K, Huibregtse JM. 115.  2010. The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15. Mol. Cell 38:722–32 [Google Scholar]
  116. Morales DJ, Lenschow DJ. 116.  2013. The antiviral activities of ISG15. J. Mol. Biol. 425:4995–5008 [Google Scholar]
  117. Lenschow DJ, Lai C, Frias-Staheli N, Giannakopoulos NV, Lutz A. 117.  et al. 2007. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. PNAS 104:1371–76 [Google Scholar]
  118. Morales DJ, Monte K, Sun L, Struckhoff JJ, Agapov E. 118.  et al. 2015. Novel mode of ISG15-mediated protection against influenza A virus and Sendai virus in mice. J. Virol. 89:337–49 [Google Scholar]
  119. Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O. 119.  et al. 2012. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science 337:1684–88 [Google Scholar]
  120. Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD. 120.  et al. 2015. Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature 517:89–93 [Google Scholar]
  121. Liberatore RA, Bieniasz PD. 121.  2011. Tetherin is a key effector of the antiretroviral activity of type I interferon in vitro and in vivo. PNAS 108:18097–101 [Google Scholar]
  122. Neil SJ, Zang T, Bieniasz PD. 122.  2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425–30 [Google Scholar]
  123. Swiecki M, Omattage NS, Brett TJ. 123.  2013. BST-2/tetherin: structural biology, viral antagonism, and immunobiology of a potent host antiviral factor. Mol. Immunol. 54:132–39 [Google Scholar]
  124. Crow MK. 124.  2014. Type I interferon in the pathogenesis of lupus. J. Immunol. 192:5459–68 [Google Scholar]
  125. Gough DJ, Messina NL, Clarke CJ, Johnstone RW, Levy DE. 125.  2012. Constitutive type I interferon modulates homeostatic balance through tonic signaling. Immunity 36:166–74 [Google Scholar]
  126. Karaghiosoff M, Steinborn R, Kovarik P, Kriegshauser G, Baccarini M. 126.  et al. 2003. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat. Immunol. 4:471–77 [Google Scholar]
  127. Davidson S, Crotta S, McCabe TM, Wack A. 127.  2014. Pathogenic potential of interferon αβ in acute influenza infection. Nat. Commun. 5:3864 [Google Scholar]
  128. Teijaro JR, Ng C, Lee AM, Sullivan BM, Sheehan KC. 128.  et al. 2013. Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 340:207–11 [Google Scholar]
  129. Wetzel JL, Fensterl V, Sen GC. 129.  2014. Sendai virus pathogenesis in mice is prevented by Ifit2 and exacerbated by interferon. J. Virol. 88:13593–601 [Google Scholar]
  130. Wilson EB, Yamada DH, Elsaesser H, Herskovitz J, Deng J. 130.  et al. 2013. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science 340:202–7 [Google Scholar]
  131. McCullers JA. 131.  2014. The co-pathogenesis of influenza viruses with bacteria in the lung. Nat. Rev. Microbiol. 12:252–62 [Google Scholar]
  132. Davidson S, Maini MK, Wack A. 132.  2015. Disease-promoting effects of type I interferons in viral, bacterial, and coinfections. J. Interferon Cytokine Res. 35:252–64 [Google Scholar]
  133. Baldridge MT, Nice TJ, McCune BT, Yokoyama CC, Kambal A. 133.  et al. 2015. Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection. Science 347:266–69 [Google Scholar]
  134. Nice TJ, Baldridge MT, McCune BT, Norman JM, Lazear HM. 134.  et al. 2015. Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity. Science 347:269–73 [Google Scholar]
  135. Kernbauer E, Ding Y, Cadwell K. 135.  2014. An enteric virus can replace the beneficial function of commensal bacteria. Nature 516:94–98 [Google Scholar]
  136. Welsch C, Jesudian A, Zeuzem S, Jacobson I. 136.  2012. New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives. Gut 61:Suppl. 1i36–46 [Google Scholar]
  137. Muir AJ, Shiffman ML, Zaman A, Yoffe B, de la Torre A. 137.  et al. 2010. Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 52:822–32 [Google Scholar]
  138. Ramos EL. 138.  2010. Preclinical and clinical development of pegylated interferon-lambda 1 in chronic hepatitis C. J. Interferon Cytokine Res. 30:591–95 [Google Scholar]
  139. Francois-Newton V, Magno de Freitas Almeida G, Payelle-Brogard B, Monneron D, Pichard-Garcia L. 139.  et al. 2011. USP18-based negative feedback control is induced by type I and type III interferons and specifically inactivates interferon α response. PLOS ONE 6:e22200 [Google Scholar]
  140. Makowska Z, Duong FH, Trincucci G, Tough DF, Heim MH. 140.  2011. Interferon-β and interferon-λ signaling is not affected by interferon-induced refractoriness to interferon-α in vivo. Hepatology 53:1154–63 [Google Scholar]
  141. Sarasin-Filipowicz M, Wang X, Yan M, Duong FH, Poli V. 141.  et al. 2009. Alpha interferon induces long-lasting refractoriness of JAK-STAT signaling in the mouse liver through induction of USP18/UBP43. Mol. Cell. Biol. 29:4841–51 [Google Scholar]
  142. Sarasin-Filipowicz M, Oakeley EJ, Duong FH, Christen V, Terracciano L. 142.  et al. 2008. Interferon signaling and treatment outcome in chronic hepatitis C. PNAS 105:7034–39 [Google Scholar]
  143. Terczynska-Dyla E, Bibert S, Duong FH, Krol I, Jorgensen S. 143.  et al. 2014. Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes. Nat. Commun. 5:5699 [Google Scholar]
  144. Urban TJ, Thompson AJ, Bradrick SS, Fellay J, Schuppan D. 144.  et al. 2010. IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology 52:1888–96 [Google Scholar]
  145. Amanzada A, Kopp W, Spengler U, Ramadori G, Mihm S. 145.  2013. Interferon-λ4 (IFNL4) transcript expression in human liver tissue samples. PLOS ONE 8:e84026 [Google Scholar]
  146. Aka PV, Kuniholm MH, Pfeiffer RM, Wang AS, Tang W. 146.  et al. 2014. Association of the IFNL4-ΔG allele with impaired spontaneous clearance of hepatitis C virus. J. Infect. Dis. 209:350–54 [Google Scholar]
  147. Randall RE, Goodbourn S. 147.  2008. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89:1–47 [Google Scholar]
  148. Cardenas WB, Loo YM, Gale M Jr., Hartman AL, Kimberlin CR. 148.  et al. 2006. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J. Virol. 80:5168–78 [Google Scholar]
  149. Krug RM. 149.  2015. Functions of the influenza A virus NS1 protein in antiviral defense. Curr. Opin. Virol. 12:1–6 [Google Scholar]
  150. Santiago FW, Covaleda LM, Sanchez-Aparicio MT, Silvas JA, Diaz-Vizarreta AC. 150.  et al. 2014. Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses. J. Virol. 88:4572–85 [Google Scholar]
  151. Goswami R, Majumdar T, Dhar J, Chattopadhyay S, Bandyopadhyay SK. 151.  et al. 2013. Viral degradasome hijacks mitochondria to suppress innate immunity. Cell Res. 23:1025–42 [Google Scholar]
  152. Horner SM, Gale M Jr. 152.  2013. Regulation of hepatic innate immunity by hepatitis C virus. Nat. Med. 19:879–88 [Google Scholar]
  153. Childs K, Randall R, Goodbourn S. 153.  2012. Paramyxovirus V proteins interact with the RNA helicase LGP2 to inhibit RIG-I-dependent interferon induction. J. Virol. 86:3411–21 [Google Scholar]
  154. Davis ME, Wang MK, Rennick LJ, Full F, Gableske S. 154.  et al. 2014. Antagonism of the phosphatase PP1 by the measles virus V protein is required for innate immune escape of MDA5. Cell Host Microbe 16:19–30 [Google Scholar]
  155. Mesman AW, Zijlstra-Willems EM, Kaptein TM, de Swart RL, Davis ME. 155.  et al. 2014. Measles virus suppresses RIG-I-like receptor activation in dendritic cells via DC-SIGN-mediated inhibition of PP1 phosphatases. Cell Host Microbe 16:31–42 [Google Scholar]
  156. Motz C, Schuhmann KM, Kirchhofer A, Moldt M, Witte G. 156.  et al. 2013. Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to inhibit antiviral signaling. Science 339:690–93 [Google Scholar]
  157. Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC. 157.  et al. 2009. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 5:439–49 [Google Scholar]
  158. Mibayashi M, Martinez-Sobrido L, Loo YM, Cardenas WB, Gale M Jr.. 158.  Garcia-Sastre A. 2007. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J. Virol. 81:514–24 [Google Scholar]
  159. Rajsbaum R, Albrecht RA, Wang MK, Maharaj NP, Versteeg GA. 159.  et al. 2012. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLOS Pathog. 8:e1003059 [Google Scholar]
  160. Gerlier D, Lyles DS. 160.  2011. Interplay between innate immunity and negative-strand RNA viruses: towards a rational model. Microbiol. Mol. Biol. Rev. 75:468–90 [Google Scholar]
  161. Li S, Min JY, Krug RM, Sen GC. 161.  2006. Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. Virology 349:13–21 [Google Scholar]
  162. Sharp TV, Schwemmle M, Jeffrey I, Laing K, Mellor H. 162.  et al. 1993. Comparative analysis of the regulation of the interferon-inducible protein kinase PKR by Epstein-Barr virus RNAs EBER-1 and EBER-2 and adenovirus VAI RNA. Nucleic Acids Res. 21:4483–90 [Google Scholar]
  163. Zhang R, Jha BK, Ogden KM, Dong B, Zhao L. 163.  et al. 2013. Homologous 2′,5′-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. PNAS 110:13114–19 [Google Scholar]
  164. Diamond MS. 164.  2014. IFIT1: a dual sensor and effector molecule that detects non-2′-O methylated viral RNA and inhibits its translation. Cytokine Growth Factor Rev. 25:543–50 [Google Scholar]
  165. Tang Y, Zhong G, Zhu L, Liu X, Shan Y. 165.  et al. 2010. Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein. J. Immunol. 184:5777–90 [Google Scholar]
  166. Elde NC, Child SJ, Geballe AP, Malik HS. 166.  2009. Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature 457:485–89 [Google Scholar]
  167. Navarini AA, Recher M, Lang KS, Georgiev P, Meury S. 167.  et al. 2006. Increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses. PNAS 103:15535–39 [Google Scholar]
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