1887

Journal of General Virology header logo

Volume 99, Issue 11

Better together: the role of IFIT protein–protein interactions in the antiviral response Open Access

Abstract

The interferon-induced proteins with tetratricopeptide repeats (IFITs) are a family of antiviral proteins conserved throughout all vertebrates. IFIT1 binds tightly to non-self RNA, particularly capped transcripts lacking methylation on the first cap-proximal nucleotide, and inhibits their translation by out-competing the cellular translation initiation apparatus. This exerts immense selection pressure on cytoplasmic RNA viruses to maintain mechanisms that protect their messenger RNA from IFIT1 recognition. However, it is becoming increasingly clear that protein–protein interactions are necessary for optimal IFIT function. Recently, IFIT1, IFIT2 and IFIT3 have been shown to form a functional complex in which IFIT3 serves as a central scaffold to regulate and/or enhance the antiviral functions of the other two components. Moreover, IFITs interact with other cellular proteins to expand their contribution to regulation of the host antiviral response by modulating innate immune signalling and apoptosis. Here, we summarize recent advances in our understanding of the IFIT complex and review how this impacts on the greater role of IFIT proteins in the innate antiviral response.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antiviral response , IFIT and interferon
© 2018 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001149
2018-09-20
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/99/11/1463.html?itemId=/content/journal/jgv/10.1099/jgv.0.001149&mimeType=html&fmt=ahah

References

  1. Liu Y, Zhang YB, Liu TK, Gui JF. Lineage-specific expansion of IFIT gene family: an insight into coevolution with IFN gene family. PLoS One 2013; 8:e66859 [View Article][PubMed]
     [Google Scholar]
  2. Fensterl V, Sen GC. The ISG56/IFIT1 gene family. J Interferon Cytokine Res 2011; 31:71–78 [View Article][PubMed]
     [Google Scholar]
  3. Zhou X, Michal JJ, Zhang L, Ding B, Lunney JK et al. Interferon induced IFIT family genes in host antiviral defense. Int J Biol Sci 2013; 9:200–208 [View Article][PubMed]
     [Google Scholar]
  4. Grandvaux N, Servant MJ, Sen GC, Balachandran S, Barber GN et al. Transcriptional profiling of interferon regulatory factor 3 target genes : direct involvement in the regulation of interferon-stimulated genes transcriptional profiling of interferon regulatory factor 3 target genes : direct involvement in the regulation; 2002; 765532–5539
  5. Pichlmair A, Lassnig C, Eberle CA, Górna MW, Baumann CL et al. IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA. Nat Immunol 2011; 12:624–630 [View Article][PubMed]
     [Google Scholar]
  6. Terenzi F, Hui DJ, Merrick WC, Sen GC. Distinct induction patterns and functions of two closely related interferon-inducible human genes, ISG54 and ISG56. J Biol Chem 2006; 281:34064–34071 [View Article][PubMed]
     [Google Scholar]
  7. Terenzi F, White C, Pal S, Williams BR, Sen GC. Tissue-specific and inducer-specific differential induction of ISG56 and ISG54 in mice. J Virol 2007; 81:8656–8665 [View Article][PubMed]
     [Google Scholar]
  8. Fensterl V, Sen GC. Interferon-induced Ifit proteins: their role in viral pathogenesis. J Virol 2015; 89:2462–2468 [View Article][PubMed]
     [Google Scholar]
  9. Daugherty MD, Schaller AM, Geballe AP, Malik HS. Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals. Elife 2016; 5:1–22 [View Article][PubMed]
     [Google Scholar]
  10. Magor KE, Miranzo Navarro D, Barber MR, Petkau K, Fleming-Canepa X et al. Defense genes missing from the flight division. Dev Comp Immunol 2013; 41:377–388 [View Article][PubMed]
     [Google Scholar]
  11. Li JJ, Wang Y, Yang CW, Ran JS, Jiang XS et al. Genotypes of IFIH1 and IFIT5 in seven chicken breeds indicated artificial selection for commercial traits influenced antiviral genes. Infect Genet Evol 2017; 56:54–61 [View Article][PubMed]
     [Google Scholar]
  12. Santhakumar D, Rohaim M, Hussein HA, Hawes P, Ferreira HL et al. Chicken interferon-induced protein with tetratricopeptide repeats 5 Antagonizes Replication of RNA Viruses. Sci Rep 2018; 8:1–20 [View Article][PubMed]
     [Google Scholar]
  13. Guo J, Hui DJ, Merrick WC, Sen GC. A new pathway of translational regulation mediated by eukaryotic initiation factor 3. EMBO J 2000; 19:6891–6899 [View Article][PubMed]
     [Google Scholar]
  14. Terenzi F, Pal S, Sen GC. Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54. Virology 2005; 340:116–124 [View Article][PubMed]
     [Google Scholar]
  15. Jackson RJ, Hellen CU, Pestova TV. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 2010; 11:113–127 [View Article][PubMed]
     [Google Scholar]
  16. Raychoudhuri A, Shrivastava S, Steele R, Kim H, Ray R et al. ISG56 and IFITM1 proteins inhibit hepatitis C virus replication. J Virol 2011; 85:12881–12889 [View Article][PubMed]
     [Google Scholar]
  17. Abbas YM, Laudenbach BT, Martínez-Montero S, Cencic R, Habjan M et al. Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2'-O methylations. Proc Natl Acad Sci USA 2017; 114:E2106E2115 [View Article][PubMed]
     [Google Scholar]
  18. Hui DJ, Bhasker CR, Merrick WC, Sen GC. Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAi. J Biol Chem 2003; 278:39477–39482 [View Article][PubMed]
     [Google Scholar]
  19. Kumar P, Sweeney TR, A SM, Skabkina O V, Hellen CUT et al. 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 2013; 42:1–18
     [Google Scholar]
  20. Habjan M, Hubel P, Lacerda L, Benda C, Holze C et al. Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA. PLoS Pathog 2013; 9:e1003663 [View Article][PubMed]
     [Google Scholar]
  21. Kimura T, Katoh H, Kayama H, Saiga H, Okuyama M et al. Ifit1 inhibits Japanese encephalitis virus replication through binding to 5' capped 2'-O unmethylated RNA. J Virol 2013; 87:9997–10003 [View Article][PubMed]
     [Google Scholar]
  22. Feng F, Yuan L, Wang YE, Crowley C, Lv Z et al. Crystal structure and nucleotide selectivity of human IFIT5/ISG58. Cell Res 2013; 23:1055–1058 [View Article][PubMed]
     [Google Scholar]
  23. Katibah GE, Lee HJ, Huizar JP, Vogan JM, Alber T et al. tRNA binding, structure, and localization of the human interferon-induced protein IFIT5. Mol Cell 2013; 49:743–750 [View Article][PubMed]
     [Google Scholar]
  24. Abbas YM, Pichlmair A, Górna MW, Superti-Furga G, Nagar B. Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins. Nature 2013; 494:60–64 [View Article][PubMed]
     [Google Scholar]
  25. Johnson B, Vanblargan LA, Xu W, White JP, Shan C et al. Human IFIT3 modulates IFIT1 RNA binding specificity and protein stability. Immunity 2018; 48:487–499 [View Article][PubMed]
     [Google Scholar]
  26. Hyde JL, Gardner CL, Kimura T, White JP, Liu G et al. A viral RNA structural element alters host recognition of nonself RNA. Science 2014; 343:783–787 [View Article][PubMed]
     [Google Scholar]
  27. Reynaud JM, Kim DY, Atasheva S, Rasalouskaya A, White JP et al. IFIT1 differentially interferes with translation and replication of alphavirus genomes and promotes induction of Type I interferon. PLoS Pathog 2015; 11:e1004863 [View Article][PubMed]
     [Google Scholar]
  28. Li SH, Dong H, Li XF, Xie X, Zhao H et al. Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation. J Virol 2013; 87:5812–5819 [View Article][PubMed]
     [Google Scholar]
  29. Daffis S, Szretter KJ, Schriewer J, Li J, Youn S et al. 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 2010; 468:452–456 [View Article][PubMed]
     [Google Scholar]
  30. Szretter KJ, Daniels BP, Cho H, Gainey MD, Yokoyama WM et al. 2'-O methylation of the viral mRNA cap by West Nile virus evades ifit1-dependent and -independent mechanisms of host restriction in vivo. PLoS Pathog 2012; 8:e1002698 [View Article][PubMed]
     [Google Scholar]
  31. Züst R, Dong H, Li XF, Chang DC, Zhang B et al. Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques. PLoS Pathog 2013; 9:e1003521 [View Article][PubMed]
     [Google Scholar]
  32. Menachery VD, Yount BL, Josset L, Gralinski LE, Scobey T et al. Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2'-o-methyltransferase activity. J Virol 2014; 88:4251–4264 [View Article][PubMed]
     [Google Scholar]
  33. Menachery VD, Gralinski LE, Mitchell HD, Dinnon KH, Leist SR et al. Middle east respiratory syndrome coronavirus nonstructural protein 16 is necessary for interferon resistance and viral pathogenesis. mSphere 2017; 2:e00346-17 [View Article][PubMed]
     [Google Scholar]
  34. Fleith RC, Mears HV, Leong XY, Sanford TJ, Emmott E et al. IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA. Nucleic Acids Res 2018; 46:5269–5285 [View Article][PubMed]
     [Google Scholar]
  35. Andrejeva J, Norsted H, Habjan M, Thiel V, Goodbourn S et al. ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis. J Gen Virol 2013; 94:59–68 [View Article][PubMed]
     [Google Scholar]
  36. Young DF, Andrejeva J, Li X, Inesta-Vaquera F, Dong C et al. Human IFIT1 inhibits mRNA translation of rubulaviruses but not other members of the Paramyxoviridae family. J Virol 2016; 90:9446–9456 [View Article][PubMed]
     [Google Scholar]
  37. Pinto AK, Williams GD, Szretter KJ, White JP, Proença-Módena JL et al. Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae families. J Virol 2015; 89:9465–9476 [View Article][PubMed]
     [Google Scholar]
  38. Terenzi F, Saikia P, Sen GC. Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1. EMBO J 2008; 27:3311–3321 [View Article][PubMed]
     [Google Scholar]
  39. Saikia P, Fensterl V, Sen GC. The inhibitory action of P56 on select functions of E1 mediates interferon's effect on human papillomavirus DNA replication. J Virol 2010; 84:13036–13039 [View Article][PubMed]
     [Google Scholar]
  40. Zhang L, Wang B, Li L, Qian DM, Yu H et al. Antiviral effects of IFIT1 in human cytomegalovirus-infected fetal astrocytes. J Med Virol 2017; 89:672–684 [View Article][PubMed]
     [Google Scholar]
  41. Blatch GL, Lässle M. The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays 1999; 21:932–939 [View Article][PubMed]
     [Google Scholar]
  42. Yang Z, Liang H, Zhou Q, Li Y, Chen H et al. Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms. Cell Res 2012; 22:1328–1338 [View Article][PubMed]
     [Google Scholar]
  43. Stawowczyk M, van Scoy S, Kumar KP, Reich NC. The interferon stimulated gene 54 promotes apoptosis. J Biol Chem 2011; 286:7257–7266 [View Article][PubMed]
     [Google Scholar]
  44. Siegfried A, Berchtold S, Manncke B, Deuschle E, Reber J et al. IFIT2 is an effector protein of type I IFN-mediated amplification of lipopolysaccharide (LPS)-induced TNF-α secretion and LPS-induced endotoxin shock. J Immunol 2013; 191:3913–3921 [View Article][PubMed]
     [Google Scholar]
  45. Chen L, Liu S, Xu F, Kong Y, Wan L et al. Inhibition of proteasome activity induces aggregation of IFIT2 in the centrosome and enhances IFIT2-induced cell apoptosis. Int J Biol Sci 2017; 13:383–390 [View Article][PubMed]
     [Google Scholar]
  46. Zhang Y, Kong Y, Liu S, Zeng L, Wan L et al. Curcumin induces apoptosis in human leukemic cell lines through an IFIT2-dependent pathway. Cancer Biol Ther 2017; 18:43–50 [View Article][PubMed]
     [Google Scholar]
  47. Jia H, Song L, Cong Q, Wang J, Xu H et al. The LIM protein AJUBA promotes colorectal cancer cell survival through suppression of JAK1/STAT1/IFIT2 network. Oncogene 2017; 36:2655–2666 [View Article][PubMed]
     [Google Scholar]
  48. Ohsugi T, Yamaguchi K, Zhu C, Ikenoue T, Furukawa Y et al. Decreased expression of interferon-induced protein 2 (IFIT2) by Wnt/β-catenin signaling confers anti-apoptotic properties to colorectal cancer cells. Oncotarget 2017; 8:100176–100186 [View Article][PubMed]
     [Google Scholar]
  49. Tang WG, Hu B, Sun HX, Sun QM, Sun C et al. Long non-coding RNA00364 represses hepatocellular carcinoma cell proliferation via modulating p-STAT3-IFIT2 signaling axis. Oncotarget 2017; 8:102006–102019 [View Article][PubMed]
     [Google Scholar]
  50. Wang Y, Zhang L, Zheng X, Zhong W, Tian X et al. Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR-645-IFIT2 axis. Cancer Lett 2016; 382:137–146 [View Article][PubMed]
     [Google Scholar]
  51. Feng X, Wang Y, Ma Z, Yang R, Liang S et al. MicroRNA-645, up-regulated in human adencarcinoma of gastric esophageal junction, inhibits apoptosis by targeting tumor suppressor IFIT2. BMC Cancer 2014; 14:1–12 [View Article][PubMed]
     [Google Scholar]
  52. Lai KC, Liu CJ, Chang KW, Lee TC. Depleting IFIT2 mediates atypical PKC signaling to enhance the migration and metastatic activity of oral squamous cell carcinoma cells. Oncogene 2013; 32:3686–3697 [View Article][PubMed]
     [Google Scholar]
  53. Tait SW, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 2010; 11:621–632 [View Article][PubMed]
     [Google Scholar]
  54. Hsu YL, Shi SF, Wu WL, Ho LJ, Lai JH. Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. PLoS One 2013; 8:e79518 [View Article][PubMed]
     [Google Scholar]
  55. Perwitasari O, Cho H, Diamond MS, Gale M. Inhibitor of κB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2 proteins define novel innate immune effector pathway against West Nile virus infection. J Biol Chem 2011; 286:44412–44423 [View Article][PubMed]
     [Google Scholar]
  56. Xiao S, Li D, Zhu HQ, Song MG, Pan XR et al. RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins. Proc Natl Acad Sci USA 2006; 103:16448–16453 [View Article][PubMed]
     [Google Scholar]
  57. Li D, Sun J, Liu W, Wang X, Bals R et al. Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB. Oncotarget 2016; 7:66032–66050 [View Article][PubMed]
     [Google Scholar]
  58. Jiang Z, Su C, Zheng C. Herpes simplex virus 1 tegument protein UL41 counteracts IFIT3 antiviral innate immunity. J Virol 2016; 90:11056–11061 [View Article][PubMed]
     [Google Scholar]
  59. Muromoto R, Nakajima M, Hirashima K, Hirao T, Kon S et al. Jun activation domain-binding protein 1 (JAB1) is required for the optimal response to interferons. J Biol Chem 2013; 288:30969–30979 [View Article][PubMed]
     [Google Scholar]
  60. Funchal GA, Jaeger N, Czepielewski RS, Machado MS, Muraro SP et al. Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils. PLoS One 2015; 10:e0124082 [View Article][PubMed]
     [Google Scholar]
  61. Stawowczyk M, Naseem S, Montoya V, Baker DP, Konopka J et al. Pathogenic effects of IFIT2 and interferon-β during fatal systemic Candida albicans infection. MBio 2018; 9:e00365-18 [View Article][PubMed]
     [Google Scholar]
  62. Berchtold S, Manncke B, Klenk J, Geisel J, Autenrieth IB et al. Forced IFIT-2 expression represses LPS induced TNF-alpha expression at posttranscriptional levels. BMC Immunol 2008; 9:75 [View Article][PubMed]
     [Google Scholar]
  63. Reshi ML, Su YC, Hong JR. RNA viruses: ROS-mediated cell death. Int J Cell Biol 2014; 2014:1–16 [View Article][PubMed]
     [Google Scholar]
  64. Ye S, Lowther S, Stambas J. Inhibition of reactive oxygen species production ameliorates inflammation induced by influenza A viruses via upregulation of SOCS1 and SOCS3. J Virol 2015; 89:2672–2683 [View Article][PubMed]
     [Google Scholar]
  65. Liu XY, Chen W, Wei B, Shan YF, Wang C. IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. J Immunol 2011; 187:2559–2568 [View Article][PubMed]
     [Google Scholar]
  66. Zhang B, Liu X, Chen W, Chen L. IFIT5 potentiates anti-viral response through enhancing innate immune signaling pathways. Acta Biochim Biophys Sin 2013; 45:867–874 [View Article][PubMed]
     [Google Scholar]
  67. Hou Z, Zhang J, Han Q, Su C, Qu J et al. Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a. Sci Rep 2016; 6:1–12 [View Article][PubMed]
     [Google Scholar]
  68. Li Y, Li C, Xue P, Zhong B, Mao AP et al. ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response. Proc Natl Acad Sci USA 2009; 106:7945–7950 [View Article][PubMed]
     [Google Scholar]
  69. Zhong B, Yang Y, Li S, Wang YY, Li Y et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 2008; 29:538–550 [View Article][PubMed]
     [Google Scholar]
  70. Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature 2011; 478:515–518 [View Article][PubMed]
     [Google Scholar]
  71. Zhao C, Denison C, Huibregtse JM, Gygi S, Krug RM. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci USA 2005; 102:10200–10205 [View Article][PubMed]
     [Google Scholar]
  72. Wang J, Dai M, Cui Y, Hou G, Deng J et al. Elevated IFIT3 contributes to abnormal overactive cGAS-STING signaling in human systemic lupus erythematosus monocytes. Arthritis Rheumatol 2018 [View Article][PubMed]
     [Google Scholar]
  73. Huang X, Shen N, Bao C, Gu Y, Wu L et al. Interferon-induced protein IFIT4 is associated with systemic lupus erythematosus and promotes differentiation of monocytes into dendritic cell-like cells. Arthritis Res Ther 2008; 10:R91 [View Article][PubMed]
     [Google Scholar]
  74. Zheng C, Zheng Z, Zhang Z, Meng J, Liu Y et al. IFIT5 positively regulates NF-κB signaling through synergizing the recruitment of IκB kinase (IKK) to TGF-β-activated kinase 1 (TAK1). Cell Signal 2015; 27:2343–2354 [View Article][PubMed]
     [Google Scholar]
  75. Napetschnig J, Wu H. Molecular basis of NF-κB signaling. Annu Rev Biophys 2013; 42:443–468 [View Article][PubMed]
     [Google Scholar]
  76. Li X, Zhu M, Brasier AR, Kudlicki AS. Inferring genome-wide functional modulatory network: a case study on NF-κB/RelA transcription factor. J Comput Biol 2015; 22:300–312 [View Article][PubMed]
     [Google Scholar]
  77. Züst R, Cervantes-Barragan L, Habjan M, Maier R, Neuman BW et al. 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 2011; 12:137–143 [View Article][PubMed]
     [Google Scholar]
  78. Cho H, Shrestha B, Sen GC, Diamond MS. A role for Ifit2 in restricting West Nile virus infection in the brain. J Virol 2013; 87:8363–8371 [View Article][PubMed]
     [Google Scholar]
  79. Rabbani MA, Ribaudo M, Guo JT, Barik S. Identification of interferon-stimulated gene proteins that inhibit human parainfluenza virus type 3. J Virol 2016; 90:11145–11156 [View Article][PubMed]
     [Google Scholar]
  80. Fensterl V, Wetzel JL, Ramachandran S, Ogino T, Stohlman SA et al. Interferon-induced Ifit2/ISG54 protects mice from lethal VSV neuropathogenesis. PLoS Pathog 2012; 8:e1002712 [View Article][PubMed]
     [Google Scholar]
  81. Guo J, Peters KL, Sen GC. Induction of the human protein P56 by interferon, double-stranded RNA, or virus infection. Virology 2000; 267:209–219 [View Article][PubMed]
     [Google Scholar]
  82. Schmeisser H, Mejido J, Balinsky CA, Morrow AN, Clark CR et al. Identification of alpha interferon-induced genes associated with antiviral activity in Daudi cells and characterization of IFIT3 as a novel antiviral gene. J Virol 2010; 84:10671–10680 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001149
Loading
Better together: the role of IFIT protein–protein interactions in the antiviral response
J. Gen. Virol. 99, 1463 (2018); https://doi.org/10.1099/jgv.0.001149
/content/journal/jgv/10.1099/jgv.0.001149
/content/journal/jgv/10.1099/jgv.0.001149
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error