1932

Abstract

Most cells respond to viral infections by activating innate immune pathways that lead to the induction of antiviral restriction factors. One such factor, viperin, was discovered almost two decades ago based on its induction during viral infection. Since then, viperin has been shown to possess activity against numerous viruses via multiple proposed mechanisms. Most recently, however, viperin was demonstrated to catalyze the conversion of cytidine triphosphate (CTP) to 3′-deoxy-3′,4′-didehydro-CTP (ddhCTP), a previously unknown ribonucleotide. Incorporation of ddhCTP causes premature termination of RNA synthesis by the RNA-dependent RNA polymerase of some viruses. To date, production of ddhCTP by viperin represents the only activity of viperin that links its enzymatic activity directly to an antiviral mechanism in human cells. This review examines the multiple antiviral mechanisms and biological functions attributed to viperin.

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2020-09-29
2024-12-08
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Literature Cited

  1. 1. 
    Gizzi AS, Grove TL, Arnold JJ, Jose J, Jangra RK et al. 2018. A naturally occurring antiviral ribonucleotide encoded by the human genome. Nature 558:610–14
    [Google Scholar]
  2. 2. 
    Zhu H, Cong JP, Shenk T 1997. Use of differential display analysis to assess the effect of human cytomegalovirus infection on the accumulation of cellular RNAs: induction of interferon-responsive RNAs. PNAS 94:13985–90
    [Google Scholar]
  3. 3. 
    Chin K-C, Cresswell P. 2001. Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus. PNAS 98:15125–30
    [Google Scholar]
  4. 4. 
    Grewal TS, Genever PG, Brabbs AC, Birch M, Skerry TM 2000. Best5: a novel interferon-inducible gene expressed during bone formation. FASEB J 14:523–31
    [Google Scholar]
  5. 5. 
    Boudinot P, Massin P, Blanco M, Riffault S, Benmansour A 1999. vig-1, a new fish gene induced by the rhabdovirus glycoprotein, has a virus-induced homologue in humans and shares conserved motifs with the MoaA family. J. Virol. 73:1846–52
    [Google Scholar]
  6. 6. 
    Boudinot P, Riffault S, Salhi S, Carrat C, Sedlik C et al. 2000. Vesicular stomatitis virus and pseudorabies virus induce a vig1/cig5 homologue in mouse dendritic cells via different pathways. J. Gen. Virol. 81:2675–82
    [Google Scholar]
  7. 7. 
    Green TJ, Speck P, Geng L, Raftos D, Beard MR, Helbig KJ 2015. Oyster viperin retains direct antiviral activity and its transcription occurs via a signalling pathway involving a heat-stable haemolymph protein. J. Gen. Virol. 96:3587–97
    [Google Scholar]
  8. 8. 
    Lei M, Liu H, Liu S, Zhang Y, Zhang S 2015. Identification and functional characterization of viperin of amphioxus Branchiostoma japonicum: implications for ancient origin of viperin-mediated antiviral response. Dev. Comp. Immunol. 53:293–302
    [Google Scholar]
  9. 9. 
    Eslamloo K, Ghorbani A, Xue X, Inkpen SM, Larijani M, Rise ML 2019. Characterization and transcript expression analyses of Atlantic cod viperin. Front. Immunol. 10:311
    [Google Scholar]
  10. 10. 
    Goossens KE, Karpala AJ, Rohringer A, Ward A, Bean AG 2015. Characterisation of chicken viperin. Mol. Immunol. 63:373–80
    [Google Scholar]
  11. 11. 
    Milic NL, Davis S, Carr JM, Isberg S, Beard MR, Helbig KJ 2015. Sequence analysis and characterisation of virally induced viperin in the saltwater crocodile (Crocodylus porosus). Dev. Comp. Immunol. 51:108–15
    [Google Scholar]
  12. 12. 
    Xu Y, Johansson M, Karlsson A 2008. Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized in mitochondria. J. Biol. Chem. 283:1563–71
    [Google Scholar]
  13. 13. 
    Kambara H, Niazi F, Kostadinova L, Moonka DK, Siegel CT et al. 2014. Negative regulation of the interferon response by an interferon-induced long non-coding RNA. Nucleic Acids Res 42:10668–80
    [Google Scholar]
  14. 14. 
    El-Diwany R, Soliman M, Sugawara S, Breitwieser F, Skaist A et al. 2018. CMPK2 and BCL-G are associated with type 1 interferon–induced HIV restriction in humans. Sci. Adv. 4:eaat0843
    [Google Scholar]
  15. 15. 
    Hinson ER, Cresswell P. 2009. The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic α-helix. PNAS 106:20452–57
    [Google Scholar]
  16. 16. 
    Hinson ER, Cresswell P. 2009. The N-terminal amphipathic α-helix of viperin mediates localization to the cytosolic face of the endoplasmic reticulum and inhibits protein secretion. J. Biol. Chem. 284:4705–12
    [Google Scholar]
  17. 17. 
    Steinbusch MMF, Caron MMJ, Surtel DAM, van den Akker GGH, van Dijk PJ et al. 2019. The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion. J. Biol. Chem. 294:5121–36
    [Google Scholar]
  18. 18. 
    Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O et al. 2011. Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Immunity 34:352–63
    [Google Scholar]
  19. 19. 
    Helbig KJ, Carr JM, Calvert JK, Wati S, Clarke JN et al. 2013. Viperin is induced following dengue virus type-2 (DENV-2) infection and has anti-viral actions requiring the C-terminal end of viperin. PLOS Neglected Trop. Dis. 7:e2178
    [Google Scholar]
  20. 20. 
    Helbig KJ, Eyre NS, Yip E, Narayana S, Li K et al. 2011. The antiviral protein viperin inhibits hepatitis C virus replication via interaction with nonstructural protein 5A. Hepatology 54:1506–17
    [Google Scholar]
  21. 21. 
    Eom J, Kim JJ, Yoon SG, Jeong H, Son S et al. 2019. Intrinsic expression of viperin regulates thermogenesis in adipose tissues. PNAS 116:17419–28
    [Google Scholar]
  22. 22. 
    Seo JY, Cresswell P. 2013. Viperin regulates cellular lipid metabolism during human cytomegalovirus infection. PLOS Pathog 9:e1003497
    [Google Scholar]
  23. 23. 
    Seo JY, Yaneva R, Hinson ER, Cresswell P 2011. Human cytomegalovirus directly induces the antiviral protein viperin to enhance infectivity. Science 332:1093–97
    [Google Scholar]
  24. 24. 
    Duschene KS, Broderick JB. 2010. The antiviral protein viperin is a radical SAM enzyme. FEBS Lett 584:1263–67
    [Google Scholar]
  25. 25. 
    Shaveta G, Shi J, Chow VT, Song J 2010. Structural characterization reveals that viperin is a radical S-adenosyl-L-methionine (SAM) enzyme. Biochem. Biophys. Res. Commun. 391:1390–95
    [Google Scholar]
  26. 26. 
    Fenwick MK, Li Y, Cresswell P, Modis Y, Ealick SE 2017. Structural studies of viperin, an antiviral radical SAM enzyme. PNAS 114:6806–11
    [Google Scholar]
  27. 27. 
    Haldar S, Paul S, Joshi N, Dasgupta A, Chattopadhyay K 2012. The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin. PLOS ONE 7:e31797
    [Google Scholar]
  28. 28. 
    Van der Hoek KH, Eyre NS, Shue B, Khantisitthiporn O, Glab-Ampi K et al. 2017. Viperin is an important host restriction factor in control of Zika virus infection. Sci. Rep. 7:4475
    [Google Scholar]
  29. 29. 
    Upadhyay AS, Vonderstein K, Pichlmair A, Stehling O, Bennett KL et al. 2014. Viperin is an iron-sulfur protein that inhibits genome synthesis of tick-borne encephalitis virus via radical SAM domain activity. Cell. Microbiol. 16:834–48
    [Google Scholar]
  30. 30. 
    Hanzelmann P, Schindelin H. 2006. Binding of 5′-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism. PNAS 103:6829–34
    [Google Scholar]
  31. 31. 
    Hanzelmann P, Schindelin H. 2004. Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans. PNAS 101:12870–75
    [Google Scholar]
  32. 32. 
    Marcotte EM, Pellegrini M, Ng HL, Rice DW, Yeates TO, Eisenberg D 1999. Detecting protein function and protein-protein interactions from genome sequences. Science 285:751–53
    [Google Scholar]
  33. 33. 
    Holliday GL, Akiva E, Meng EC, Brown SD, Calhoun S et al. 2018. Atlas of the radical SAM superfamily: divergent evolution of function using a “plug and play” domain. Methods Enzymol 606:1–71
    [Google Scholar]
  34. 34. 
    Minnihan EC, Nocera DG, Stubbe J 2013. Reversible, long-range radical transfer in E. coli class Ia ribonucleotide reductase. Acc. Chem. Res. 46:2524–35
    [Google Scholar]
  35. 35. 
    Schwarz HA, Dodson RW. 1989. Reduction potentials of CO2 and the alcohol radicals. J. Phys. Chem. 93:409–14
    [Google Scholar]
  36. 36. 
    Silakov A, Grove TL, Radle MI, Bauerle MR, Green MT et al. 2014. Characterization of a cross-linked protein nucleic acid substrate radical in the reaction catalyzed by RlmN. J. Am. Chem. Soc. 136:8221–28
    [Google Scholar]
  37. 37. 
    Grove TL, Radle MI, Krebs C, Booker SJ 2011. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement and radical generation. J. Am. Chem. Soc. 133:19586–89
    [Google Scholar]
  38. 38. 
    Grove TL, Livada J, Schwalm EL, Green MT, Booker SJ, Silakov A 2013. A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr. Nat. Chem. Biol. 9:422–27
    [Google Scholar]
  39. 39. 
    Fenwick MK, Su D, Dong M, Lin H, Ealick SE 2020. Structural basis of substrate selectivity of viperin. Biochemistry 59:652–62
    [Google Scholar]
  40. 40. 
    Honarmand Ebrahimi K, Carr SB, McCullagh J, Wickens J, Rees NH et al. 2017. The radical-SAM enzyme Viperin catalyzes reductive addition of a 5′-deoxyadenosyl radical to UDP-glucose in vitro. . FEBS Lett 591:2394–405
    [Google Scholar]
  41. 41. 
    Chakravarti A, Selvadurai K, Shahoei R, Lee H, Fatma S et al. 2018. Reconstitution and substrate specificity for isopentenyl pyrophosphate of the antiviral radical SAM enzyme viperin. J. Biol. Chem. 293:14122–33
    [Google Scholar]
  42. 42. 
    Eom J, Yoo J, Kim JJ, Lee JB, Choi W et al. 2018. Viperin deficiency promotes polarization of macrophages and secretion of M1 and M2 cytokines. Immune Netw 18:e32
    [Google Scholar]
  43. 43. 
    Severa M, Coccia EM, Fitzgerald KA 2006. Toll-like receptor-dependent and -independent viperin gene expression and counter-regulation by PRDI-binding factor-1/BLIMP1. J. Biol. Chem. 281:26188–95
    [Google Scholar]
  44. 44. 
    Weiss G, Rasmussen S, Zeuthen LH, Nielsen BN, Jarmer H et al. 2010. Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism. Immunology 131:268–81
    [Google Scholar]
  45. 45. 
    Luo F, Liu H, Yang S, Fang Y, Zhao Z et al. 2019. Nonreceptor tyrosine kinase c-Abl- and Arg-mediated IRF3 phosphorylation regulates innate immune responses by promoting type I IFN production. J. Immunol. 202:2254–65
    [Google Scholar]
  46. 46. 
    Olofsson PS, Jatta K, Wagsater D, Gredmark S, Hedin U et al. 2005. The antiviral cytomegalovirus inducible gene 5/viperin is expressed in atherosclerosis and regulated by proinflammatory agents. Arterioscler. Thromb. Vasc. Biol. 25:e113–113
    [Google Scholar]
  47. 47. 
    Lazear HM, Schoggins JW, Diamond MS 2019. Shared and distinct functions of type I and type III interferons. Immunity 50:907–23
    [Google Scholar]
  48. 48. 
    Pervolaraki K, Rastgou Talemi S, Albrecht D, Bormann F, Bamford C et al. 2018. Differential induction of interferon stimulated genes between type I and type III interferons is independent of interferon receptor abundance. PLOS Pathog 14:e1007420
    [Google Scholar]
  49. 49. 
    Zhou Z, Hamming OJ, Ank N, Paludan SR, Nielsen AL, Hartmann R 2007. Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases. J. Virol. 81:7749–58
    [Google Scholar]
  50. 50. 
    Duschene KS, Broderick JB. 2012. Viperin: a radical response to viral infection. Biomol. Concepts 3:255–66
    [Google Scholar]
  51. 51. 
    Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S et al. 2009. Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity 30:802–16
    [Google Scholar]
  52. 52. 
    Keller AD, Maniatis T. 1991. Identification and characterization of a novel repressor of beta-interferon gene expression. Genes Dev 5:868–79
    [Google Scholar]
  53. 53. 
    Mattijssen S, Hinson ER, Onnekink C, Hermanns P, Zabel B et al. 2011. Viperin mRNA is a novel target for the human RNase MRP/RNase P endoribonuclease. Cell. Mol. Life Sci. 68:2469–80
    [Google Scholar]
  54. 54. 
    Rivieccio MA, Suh H-S, Zhao Y, Zhao M-L, Chin KC et al. 2006. TLR3 ligation activates an antiviral response in human fetal astrocytes: a role for viperin/cig5. J. Immunol. 177:4735–41
    [Google Scholar]
  55. 55. 
    Grandvaux N, Servant MJ, tenOever B, Sen GC, Balachandran S et al. 2002. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J. Virol. 76:5532–39
    [Google Scholar]
  56. 56. 
    Chan Y-L, Chang T-H, Liao C-L, Lin Y-L 2008. The cellular antiviral protein viperin is attenuated by proteasome-mediated protein degradation in Japanese encephalitis virus-infected cells. J. Virol. 82:10455–64
    [Google Scholar]
  57. 57. 
    DeFilippis VR, Robinson B, Keck TM, Hansen SG, Nelson JA, Früh KJ 2006. Interferon regulatory factor 3 is necessary for induction of antiviral genes during human cytomegalovirus infection. J. Virol. 80:1032–37
    [Google Scholar]
  58. 58. 
    Ashley CL, Abendroth A, McSharry BP, Slobedman B 2019. Interferon-independent upregulation of interferon-stimulated genes during human cytomegalovirus infection is dependent on IRF3 expression. Viruses 11:246
    [Google Scholar]
  59. 59. 
    White LK, Sali T, Alvarado D, Gatti E, Pierre P et al. 2011. Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff. J. Virol. 85:606–20
    [Google Scholar]
  60. 60. 
    Stirnweiss A, Ksienzyk A, Klages K, Rand U, Grashoff M et al. 2010. IFN regulatory factor-1 bypasses IFN-mediated antiviral effects through viperin gene induction. J. Immunol. 184:5179–85
    [Google Scholar]
  61. 61. 
    Vazquez C, Horner SM. 2015. MAVS coordination of antiviral innate immunity. J. Virol. 89:6974–77
    [Google Scholar]
  62. 62. 
    Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C et al. 2010. Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141:668–81
    [Google Scholar]
  63. 63. 
    Odendall C, Dixit E, Stavru F, Bierne H, Franz KM et al. 2014. Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nat. Immunol. 15:717–26
    [Google Scholar]
  64. 64. 
    Sommereyns C, Paul S, Staeheli P, Michiels T 2008. IFN-lambda (IFN-λ) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLOS Pathog 4:e1000017
    [Google Scholar]
  65. 65. 
    Forero A, Ozarkar S, Li H, Lee CH, Hemann EA et al. 2019. Differential activation of the transcription factor IRF1 underlies the distinct immune responses elicited by type I and type III interferons. Immunity 51:451–64
    [Google Scholar]
  66. 66. 
    Yamane D, Feng H, Rivera-Serrano EE, Selitsky SR, Hirai-Yuki A et al. 2019. Basal expression of interferon regulatory factor 1 drives intrinsic hepatocyte resistance to multiple RNA viruses. Nat. Microbiol. 4:1096–104
    [Google Scholar]
  67. 67. 
    Panda D, Gjinaj E, Bachu M, Squire E, Novatt H et al. 2019. IRF1 maintains optimal constitutive expression of antiviral genes and regulates the early antiviral response. Front. Immunol. 10:1019
    [Google Scholar]
  68. 68. 
    Hinson ER, Joshi NS, Chen JH, Rahner C, Jung YW et al. 2010. Viperin is highly induced in neutrophils and macrophages during acute and chronic lymphocytic choriomeningitis virus infection. J. Immunol. 184:5723–31
    [Google Scholar]
  69. 69. 
    Bai L, Dong J, Liu Z, Rao Y, Feng P, Lan K 2019. Viperin catalyzes methionine oxidation to promote protein expression and function of helicases. Sci. Adv. 5:eaax1031
    [Google Scholar]
  70. 70. 
    Wang X, Hinson ER, Cresswell P 2007. The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe 2:96–105
    [Google Scholar]
  71. 71. 
    Upadhyay AS, Stehling O, Panayiotou C, Rösser R, Lill R, Överby AK 2017. Cellular requirements for iron–sulfur cluster insertion into the antiviral radical SAM protein viperin. J. Biol. Chem. 292:13879–89
    [Google Scholar]
  72. 72. 
    Seo JY, Yaneva R, Cresswell P 2011. Viperin: a multifunctional, interferon-inducible protein that regulates virus replication. Cell Host Microbe 10:534–39
    [Google Scholar]
  73. 73. 
    Hee JS, Cresswell P. 2017. Viperin interaction with mitochondrial antiviral signaling protein (MAVS) limits viperin-mediated inhibition of the interferon response in macrophages. PLOS ONE 12:e0172236
    [Google Scholar]
  74. 74. 
    Yuan Y, Miao Y, Qian L, Zhang Y, Liu C et al. 2019. Targeting UBE4A revives viperin protein in epithelium to enhance host antiviral defense. Mol. Cell 77:734–47
    [Google Scholar]
  75. 75. 
    Jiang D, Guo H, Xu C, Chang J, Gu B et al. 2008. Identification of three interferon-inducible cellular enzymes that inhibit the replication of hepatitis C virus. J. Virol. 82:1665–78
    [Google Scholar]
  76. 76. 
    Jiang D, Weidner JM, Qing M, Pan X-B, Guo H et al. 2010. Identification of five interferon-induced cellular proteins that inhibit West Nile virus and dengue virus infections. J. Virol. 84:8332–41
    [Google Scholar]
  77. 77. 
    Panayiotou C, Lindqvist R, Kurhade C, Vonderstein K, Pasto J et al. 2018. Viperin restricts Zika virus and tick-borne encephalitis virus replication by targeting NS3 for proteasomal degradation. J. Virol. 92:e02054-17
    [Google Scholar]
  78. 78. 
    Wang S, Wu X, Pan T, Song W, Wang Y et al. 2012. Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33. J. Gen. Virol. 93:83–92
    [Google Scholar]
  79. 79. 
    Vanwalscappel B, Gadea G, Despres P 2019. A viperin mutant bearing the K358R substitution lost its anti-ZIKA virus activity. Int. J. Mol. Sci. 20:1574
    [Google Scholar]
  80. 80. 
    Mikulecky P, Andreeva E, Amara P, Weissenhorn W, Nicolet Y, Macheboeuf P 2018. Human viperin catalyzes the modification of GPP and FPP potentially affecting cholesterol synthesis. FEBS Lett 592:199–208
    [Google Scholar]
  81. 81. 
    Teng TS, Foo SS, Simamarta D, Lum FM, Teo TH et al. 2012. Viperin restricts chikungunya virus replication and pathology. J. Clin. Invest. 122:4447–60
    [Google Scholar]
  82. 82. 
    Vonderstein K, Nilsson E, Hubel P, Nygård Skalman L, Upadhyay A et al. 2018. Viperin targets flavivirus virulence by inducing assembly of noninfectious capsid particles. J. Virol. 92:e01751-17
    [Google Scholar]
  83. 83. 
    Makins C, Ghosh S, Roman-Melendez GD, Malec PA, Kennedy RT, Marsh EN 2016. Does viperin function as a radical S-adenosyl-l-methionine-dependent enzyme in regulating farnesylpyrophosphate synthase expression and activity. ? J. Biol. Chem. 291:26806–15
    [Google Scholar]
  84. 84. 
    Nasr N, Maddocks S, Turville SG, Harman AN, Woolger N et al. 2012. HIV-1 infection of human macrophages directly induces viperin which inhibits viral production. Blood 120:778–88
    [Google Scholar]
  85. 85. 
    Kurokawa C, Iankov ID, Galanis E 2019. A key anti-viral protein, RSAD2/VIPERIN, restricts the release of measles virus from infected cells. Virus Res 263:145–50
    [Google Scholar]
  86. 86. 
    Tang H-B, Lu Z-L, Wei X-K, Zhong T-Z, Zhong Y-Z et al. 2016. Viperin inhibits rabies virus replication via reduced cholesterol and sphingomyelin and is regulated upstream by TLR4. Sci. Rep. 6:30529
    [Google Scholar]
  87. 87. 
    Schoors S, Bruning U, Missiaen R, Queiroz KC, Borgers G et al. 2015. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 520:192–97
    [Google Scholar]
  88. 88. 
    Qiu L-Q, Cresswell P, Chin K-C 2009. Viperin is required for optimal Th2 responses and T-cell receptor–mediated activation of NF-κB and AP-1. Blood 113:3520–29
    [Google Scholar]
  89. 89. 
    Dumbrepatil AB, Ghosh S, Zegalia KA, Malec PA, Hoff JD et al. 2019. Viperin interacts with the kinase IRAK1 and the E3 ubiquitin ligase TRAF6, coupling innate immune signaling to antiviral ribonucleotide synthesis. J. Biol. Chem. 294:6888–98
    [Google Scholar]
  90. 90. 
    Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S et al. 2018. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560:198–203
    [Google Scholar]
  91. 91. 
    Das A, Yang C-S, Arifuzzaman S, Kim S, Kim SY et al. 2018. High-resolution mapping and dynamics of the transcriptome, transcription factors, and transcription co-factor networks in classically and alternatively activated macrophages. Front. Immunol. 9:22
    [Google Scholar]
  92. 92. 
    Dukhovny A, Shlomai A, Sklan EH 2018. The antiviral protein Viperin suppresses T7 promoter dependent RNA synthesis-possible implications for its antiviral activity. Sci. Rep. 8:8100
    [Google Scholar]
  93. 93. 
    Helbig KJ, Teh MY, Crosse KM, Monson EA, Smith M et al. 2019. The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro. Sci. Rep 9:15598
    [Google Scholar]
  94. 94. 
    Szretter KJ, Brien JD, Thackray LB, Virgin HW, Cresswell P, Diamond MS 2011. The interferon-inducible gene viperin restricts West Nile virus pathogenesis. J. Virol. 85:11557–66
    [Google Scholar]
  95. 95. 
    Vanwalscappel B, Tada T, Landau NR 2018. Toll-like receptor agonist R848 blocks Zika virus replication by inducing the antiviral protein viperin. Virology 522:199–208
    [Google Scholar]
  96. 96. 
    Lindqvist R, Kurhade C, Gilthorpe JD, Överby AK 2018. Cell-type- and region-specific restriction of neurotropic flavivirus infection by viperin. J. Neuroinflamm. 15:80
    [Google Scholar]
  97. 97. 
    Proud D, Turner RB, Winther B, Wiehler S, Tiesman JP et al. 2008. Gene expression profiles during in vivo human rhinovirus infection: insights into the host response. Am. J. Respir. Crit. Care Med. 178:962–68
    [Google Scholar]
  98. 98. 
    Wei C, Zheng C, Sun J, Luo D, Tang Y et al. 2018. Viperin inhibits enterovirus A71 replication by interacting with viral 2C protein. Viruses 11:13
    [Google Scholar]
  99. 99. 
    Zhang Y, Burke CW, Ryman KD, Klimstra WB 2007. Identification and characterization of interferon-induced proteins that inhibit alphavirus replication. J. Virol. 81:11246–55
    [Google Scholar]
  100. 100. 
    Tan KS, Olfat F, Phoon MC, Hsu JP, Howe JLC et al. 2012. In vivo and in vitro studies on the antiviral activities of viperin against influenza H1N1 virus infection. J. Gen. Virol. 93:1269–77
    [Google Scholar]
  101. 101. 
    Pena Carcamo JR, Morell ML, Vazquez CA, Vatansever S, Upadhyay AS et al. 2018. The interplay between viperin antiviral activity, lipid droplets and Junín mammarenavirus multiplication. Virology 514:216–29
    [Google Scholar]
  102. 102. 
    Carlton-Smith C, Elliott RM. 2012. Viperin, MTAP44, and protein kinase R contribute to the interferon-induced inhibition of Bunyamwera Orthobunyavirus replication. J. Virol. 86:11548–57
    [Google Scholar]
  103. 103. 
    McGillivary G, Jordan ZB, Peeples ME, Bakaletz LO 2013. Replication of respiratory syncytial virus is inhibited by the host defense molecule viperin. J. Innate Immunity 5:60–71
    [Google Scholar]
  104. 104. 
    Jumat MR, Huong TN, Ravi LI, Stanford R, Tan BH, Sugrue RJ 2015. Viperin protein expression inhibits the late stage of respiratory syncytial virus morphogenesis. Antivir. Res. 114:11–20
    [Google Scholar]
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