Innate immune responses in RNA viral infection

Abstract

RNA viruses cause a multitude of human diseases, including several pandemic events in the past century. Upon viral invasion, the innate immune system responds rapidly and plays a key role in activating the adaptive immune system. In the innate immune system, the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral responses. Macrophages, dendritic cells, and natural killer cells are the principal innate immune components that exert antiviral activities. In this review, the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly summarized. Besides the main role of immune cells in combating viral infection, the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was discussed. This knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

Keywords

innate immune / viral infection / intercellular signaling / metabolic changes / epigenetic changes

References

[1] Poltronieri P, Sun B, Mallardo M. RNA viruses: RNA roles in pathogenesis, coreplication and viral load. Curr Genomics 2015; 16(5): 327–335

[2] Broz P, Monack DM. Newly described pattern recognition receptors team up against intracellular pathogens. Nat Rev Immunol 2013; 13(8): 551–565

[3] Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001; 14(4): 778–809

[4] Jensen S, Thomsen AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol 2012; 86(6): 2900–2910

[5] Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4(7): 499–511

[6] de Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, Bates EE, Caux C. Recognition of double-stranded RNA by human Toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem 2005; 280(46): 38133–38145

[7] Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004; 303(5663): 1529–1531

[8] Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 2004; 303(5663): 1526–1529

[9] Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010; 140(6): 805–820

[10] Krug A, French AR, Barchet W, Fischer JA, Dzionek A, Pingel JT, Orihuela MM, Akira S, Yokoyama WM, Colonna M. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 2004; 21(1): 107–119

[11] Lai JH, Wang MY, Huang CY, Wu CH, Hung LF, Yang CY, Ke PY, Luo SF, Liu SJ, Ho LJ. Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells. EMBO Rep 2018; 19(8): 19

[12] Yoneyama M, Fujita T. RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev 2009; 227(1): 54–65

[13] Takahasi K, Yoneyama M, Nishihori T, Hirai R, Kumeta H, Narita R, Gale M Jr, Inagaki F, Fujita T. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell 2008; 29(4): 428–440

[14] Chiang JJ, Sparrer KMJ, van Gent M, Lässig C, Huang T, Osterrieder N, Hopfner KP, Gack MU. Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity. Nat Immunol 2018; 19(1): 53–62

[15] Jiang M, Zhang S, Yang Z, Lin H, Zhu J, Liu L, Wang W, Liu S, Liu W, Ma Y, Zhang L, Cao X.Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response. Cell 2018; 173: 906–919.e13 PMID: 29706547

[16] Zhao Y, Ye X, Dunker W, Song Y, Karijolich J. RIG-I like receptor sensing of host RNAs facilitates the cell-intrinsic immune response to KSHV infection. Nat Commun 2018; 9(1): 4841

[17] Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 2011; 146(3): 448–461

[18] Son KN, Liang Z, Lipton HL. Double-stranded RNA is detected by immunofluorescence analysis in RNA and DNA virus infections, including those by negative-stranded RNA viruses. J Virol 2015; 89(18): 9383–9392

[19] Sanchez David RY, Combredet C, Najburg V, Millot GA, Beauclair G, Schwikowski B, Léger T, Camadro JM, Jacob Y, Bellalou J, Jouvenet N, Tangy F, Komarova AV. LGP2 binds to PACT to regulate RIG-I- and MDA5-mediated antiviral responses. Sci Signal 2019; 12(601): eaar3993

[20] Komuro A, Horvath CM. RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2. J Virol 2006; 80(24): 12332–12342

[21] Saito T, Hirai R, Loo YM, Owen D, Johnson CL, Sinha SC, Akira S, Fujita T, Gale M Jr. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA 2007; 104(2): 582–587

[22] Brown GD, Willment JA, Whitehead L. C-type lectins in immunity and homeostasis. Nat Rev Immunol 2018; 18(6): 374–389

[23] East L, Isacke CM. The mannose receptor family. Biochim Biophys Acta 2002; 1572(2-3): 364–386

[24] Miller JL, de Wet BJ, Martinez-Pomares L, Radcliffe CM, Dwek RA, Rudd PM, Gordon S. The mannose receptor mediates dengue virus infection of macrophages. PLoS Pathog 2008; 4(2): e17

[25] Gürtler C, Bowie AG. Innate immune detection of microbial nucleic acids. Trends Microbiol 2013; 21(8): 413–420

[26] Carpenter S, Ricci EP, Mercier BC, Moore MJ, Fitzgerald KA. Post-transcriptional regulation of gene expression in innate immunity. Nat Rev Immunol 2014; 14(6): 361–376

[27] Cao X. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat Rev Immunol 2016; 16(1): 35–50

[28] Tong AJ, Liu X, Thomas BJ, Lissner MM, Baker MR, Senagolage MD, Allred AL, Barish GD, Smale ST. A stringent systems approach uncovers gene-specific mechanisms regulating inflammation. Cell 2016; 165(1): 165–179

[29] Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 2006; 6(9): 644–658

[30] Högner K, Wolff T, Pleschka S, Plog S, Gruber AD, Kalinke U, Walmrath HD, Bodner J, Gattenlöhner S, Lewe-Schlosser P, Matrosovich M, Seeger W, Lohmeyer J, Herold S. Macrophage-expressed IFN-b contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog 2013; 9(2): e1003188

[31] Kallfass C, Lienenklaus S, Weiss S, Staeheli P. Visualizing the β interferon response in mice during infection with influenza A viruses expressing or lacking nonstructural protein 1. J Virol 2013; 87(12): 6925–6930

[32] Jewell NA, Vaghefi N, Mertz SE, Akter P, Peebles RS Jr, Bakaletz LO, Durbin RK, Flaño E, Durbin JE. Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo. J Virol 2007; 81(18): 9790–9800

[33] Pothlichet J, Meunier I, Davis BK, Ting JP, Skamene E, von Messling V, Vidal SM. Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells. PLoS Pathog 2013; 9(4): e1003256

[34] Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 2009; 30(4): 556–565

[35] Man SM, Kanneganti TD. Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat Rev Immunol 2016; 16(1): 7–21

[36] von Moltke J, Ayres JS, Kofoed EM, Chavarría-Smith J, Vance RE. Recognition of bacteria by inflammasomes. Annu Rev Immunol 2013; 31(1): 73–106

[37] Shi CS, Nabar NR, Huang NN, Kehrl JH. SARS-coronavirus open reading frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes. Cell Death Discov 2019; 5(1): 101

[38] Wong HH, Fung TS, Fang S, Huang M, Le MT, Liu DX. Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3. Virology 2018; 515: 165–175

[39] Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 2013; 339(6121): 786–791

[40] Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 2013; 339(6121): 826–830

[41] Zheng Y, Liu Q, Wu Y, Ma L, Zhang Z, Liu T, Jin S, She Y, Li YP, Cui J. Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis. EMBO J 2018; 37(18): e99347

[42] Farhat K, Riekenberg S, Heine H, Debarry J, Lang R, Mages J, Buwitt-Beckmann U, Röschmann K, Jung G, Wiesmüller KH, Ulmer AJ. Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling. J Leukoc Biol 2008; 83(3): 692–701

[43] Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 2007; 130(6): 1071–1082

[44] Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 1999; 162(7): 3749–3752

[45] Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 1999; 274(25): 17406–17409

[46] Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 2001; 410(6832): 1099–1103

[47] Place DE, Kanneganti TD. Recent advances in inflammasome biology. Curr Opin Immunol 2018; 50: 32–38

[48] Martinez FO, Gordon S. The evolution of our understanding of macrophages and translation of findings toward the clinic. Expert Rev Clin Immunol 2015; 11(1): 5–13

[49] de Las Casas-Engel M, Corbí AL. Serotonin modulation of macrophage polarization: inflammation and beyond. Adv Exp Med Biol 2014; 824: 89–115

[50] Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 2014; 14(6): 392–404

[51] Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I, De Nardo D, Gohel TD, Emde M, Schmidleithner L, Ganesan H, Nino-Castro A, Mallmann MR, Labzin L, Theis H, Kraut M, Beyer M, Latz E, Freeman TC, Ulas T, Schultze JL. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 2014; 40(2): 274–288

[52] Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J, Udalova I, van Ginderachter JA, Vogel SN, Wynn TA. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41(1): 14–20

[53] Domínguez-Soto A, de las Casas-Engel M, Bragado R, Medina-Echeverz J, Aragoneses-Fenoll L, Martín-Gayo E, van Rooijen N, Berraondo P, Toribio ML, Moro MA, Cuartero I, Castrillo A, Sancho D, Sánchez-Torres C, Bruhns P, Sánchez-Ramón S, Corbí AL. Intravenous immunoglobulin promotes antitumor responses by modulating macrophage polarization. J Immunol 2014; 193(10): 5181–5189

[54] Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014; 6: 13

[55] Gad HH, Dellgren C, Hamming OJ, Vends S, Paludan SR, Hartmann R. Interferon-λ is functionally an interferon but structurally related to the interleukin-10 family. J Biol Chem 2009; 284(31): 20869–20875

[56] Sang Y, Brichalli W, Rowland RR, Blecha F. Genome-wide analysis of antiviral signature genes in porcine macrophages at different activation statuses. PLoS One 2014; 9(2): e87613

[57] Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem 2007; 282(28): 20059–20063

[58] McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I interferons in infectious disease. Nat Rev Immunol 2015; 15(2): 87–103 doi:10.1038/nri3787

[59] Koch S, Finotto S. Role of interferon-l in allergic asthma. J Innate Immun 2015; 7(3): 224–230

[60] Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol 2014; 14(1): 36–49

[61] Zhao X, Dai J, Xiao X, Wu L, Zeng J, Sheng J, Su J, Chen X, Wang G, Li K. PI3K/Akt signaling pathway modulates influenza virus induced mouse alveolar macrophage polarization to M1/M2b. PLoS One 2014; 9(8): e104506

[62] Yang Y, Zhang R, Xia F, Zou T, Huang A, Xiong S, Zhang J. LPS converts Gr-1⁺CD115⁺ myeloid-derived suppressor cells from M2 to M1 via P38 MAPK. Exp Cell Res 2013; 319(12): 1774–1783

[63] González-Navajas JM, Lee J, David M, Raz E. Immunomodulatory functions of type I interferons. Nat Rev Immunol 2012; 12(2): 125–135

[64] Jaume M, Yip MS, Cheung CY, Leung HL, Li PH, Kien F, Dutry I, Callendret B, Escriou N, Altmeyer R, Nal B, Daëron M, Bruzzone R, Peiris JS. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcgR pathway. J Virol 2011; 85(20): 10582–10597

[65] Yip MS, Leung NH, Cheung CY, Li PH, Lee HH, Daëron M, Peiris JS, Bruzzone R, Jaume M. Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus. Virol J 2014; 11(1): 82

[66] Zhao J, Zhao J, Van Rooijen N, Perlman S. Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice. PLoS Pathog 2009; 5(10): e1000636

[67] Tatano Y, Shimizu T, Tomioka H. Unique macrophages different from M1/M2 macrophages inhibit T cell mitogenesis while upregulating Th17 polarization. Sci Rep 2014; 4(1): 4146

[68] Darwish I, Mubareka S, Liles WC. Immunomodulatory therapy for severe influenza. Expert Rev Anti Infect Ther 2011; 9(7): 807–822

[69] Boehler RM, Kuo R, Shin S, Goodman AG, Pilecki MA, Gower RM, Leonard JN, Shea LD. Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype. Biotechnol Bioeng 2014; 111(6): 1210–1221

[70] Richter K, Perriard G, Behrendt R, Schwendener RA, Sexl V, Dunn R, Kamanaka M, Flavell RA, Roers A, Oxenius A. Macrophage and T cell produced IL-10 promotes viral chronicity. PLoS Pathog 2013; 9(11): e1003735

[71] Zdrenghea MT, Makrinioti H, Muresan A, Johnston SL, Stanciu LA. The role of macrophage IL-10/innate IFN interplay during virus-induced asthma. Rev Med Virol 2015; 25(1): 33–49

[72] Ouyang P, Rakus K, van Beurden SJ, Westphal AH, Davison AJ, Gatherer D, Vanderplasschen AF. IL-10 encoded by viruses: a remarkable example of independent acquisition of a cellular gene by viruses and its subsequent evolution in the viral genome. J Gen Virol 2014; 95(Pt 2): 245–262

[73] Wilson EB, Brooks DG. The role of IL-10 in regulating immunity to persistent viral infections. Curr Top Microbiol Immunol 2011; 350: 39–65

[74] Perkins DJ, Polumuri SK, Pennini ME, Lai W, Xie P, Vogel SN. Reprogramming of murine macrophages through TLR2 confers viral resistance via TRAF3-mediated, enhanced interferon production. PLoS Pathog 2013; 9(7): e1003479

[75] Patel MC, Shirey KA, Pletneva LM, Boukhvalova MS, Garzino-Demo A, Vogel SN, Blanco JC. Novel drugs targeting Toll-like receptors for antiviral therapy. Future Virol 2014; 9(9): 811–829

[76] Zhang B, Chassaing B, Shi Z, Uchiyama R, Zhang Z, Denning TL, Crawford SE, Pruijssers AJ, Iskarpatyoti JA, Estes MK, Dermody TS, Ouyang W, Williams IR, Vijay-Kumar M, Gewirtz AT. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Science 2014; 346(6211): 861–865

[77] Liu K, Nussenzweig MC. Origin and development of dendritic cells. Immunol Rev 2010; 234(1): 45–54

[78] Pulendran B, Palucka K, Banchereau J. Sensing pathogens and tuning immune responses. Science 2001; 293(5528): 253–256

[79] Collin M, McGovern N, Haniffa M. Human dendritic cell subsets. Immunology 2013; 140(1): 22–30

[80] Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, Leenen PJ, Liu YJ, MacPherson G, Randolph GJ, Scherberich J, Schmitz J, Shortman K, Sozzani S, Strobl H, Zembala M, Austyn JM, Lutz MB. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116(16): e74–e80

[81] Moretta A. Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol 2002; 2(12): 957–964

[82] Swiecki M, Colonna M. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol 2015; 15(8): 471–485

[83] Webster B, Assil S, Dreux M. Cell-cell sensing of viral infection by plasmacytoid dendritic cells. J Virol 2016; 90(22): 10050–10053

[84] Dessouki O, Kamiya Y, Nagahama H, Tanaka M, Suzu S, Sasaki Y, Okada S. Chronic hepatitis C viral infection reduces NK cell frequency and suppresses cytokine secretion: reversion by anti-viral treatment. Biochem Biophys Res Commun 2010; 393(2): 331–337

[85] Jinushi M, Takehara T, Tatsumi T, Kanto T, Groh V, Spies T, Suzuki T, Miyagi T, Hayashi N. Autocrine/paracrine IL-15 that is required for type I IFN-mediated dendritic cell expression of MHC class I-related chain A and B is impaired in hepatitis C virus infection. J Immunol 2003; 171(10): 5423–5429

[86] Kiessling R, Klein E, Wigzell H. “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 1975; 5(2): 112–117

[87] Hammer Q, Rückert T, Romagnani C. Natural killer cell specificity for viral infections. Nat Immunol 2018; 19(8): 800–808 doi:10.1038/s41590-018-0163-6

[88] Kronstad LM, Seiler C, Vergara R, Holmes SP, Blish CA. Differential induction of IFN-a and modulation of CD112 and CD54 expression govern the magnitude of NK cell IFN-g response to influenza A viruses. J Immunol 2018; 201(7): 2117–2131

[89] Martín-Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M, Lanzavecchia A, Sallusto F. Induced recruitment of NK cells to lymph nodes provides IFN-γ for T(H)1 priming. Nat Immunol 2004; 5(12): 1260–1265

[90] Wagstaffe HR, Nielsen CM, Riley EM, Goodier MR. IL-15 promotes polyfunctional NK cell responses to influenza by boosting IL-12 production. J Immunol 2018; 200(8): 2738–2747

[91] Zamora AE, Aguilar EG, Sungur CM, Khuat LT, Dunai C, Lochhead GR, Du J, Pomeroy C, Blazar BR, Longo DL, Venstrom JM, Baumgarth N, Murphy WJ. Licensing delineates helper and effector NK cell subsets during viral infection. JCI Insight 2017; 2(10): e87032

[92] Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol 2008; 9(5): 503–510

[93] Liu LL, Landskron J, Ask EH, Enqvist M, Sohlberg E, Traherne JA, Hammer Q, Goodridge JP, Larsson S, Jayaraman J, Oei VYS, Schaffer M, Taskén K, Ljunggren HG, Romagnani C, Trowsdale J, Malmberg KJ, Béziat V. Critical role of CD2 co-stimulation in adaptive natural killer cell responses revealed in NKG2C-deficient humans. Cell Reports 2016; 15(5): 1088–1099

[94] Luetke-Eversloh M, Hammer Q, Durek P, Nordström K, Gasparoni G, Pink M, Hamann A, Walter J, Chang HD, Dong J, Romagnani C. Human cytomegalovirus drives epigenetic imprinting of the IFNG locus in NKG2Chi natural killer cells. PLoS Pathog 2014; 10(10): e1004441

[95] Nguyen KB, Salazar-Mather TP, Dalod MY, Van Deusen JB, Wei XQ, Liew FY, Caligiuri MA, Durbin JE, Biron CA. Coordinated and distinct roles for IFN-αβ, IL-12, and IL-15 regulation of NK cell responses to viral infection. J Immunol 2002; 169(8): 4279–4287

[96] Madera S, Rapp M, Firth MA, Beilke JN, Lanier LL, Sun JC. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide. J Exp Med 2016; 213(2): 225–233

[97] Strauss-Albee DM, Fukuyama J, Liang EC, Yao Y, Jarrell JA, Drake AL, Kinuthia J, Montgomery RR, John-Stewart G, Holmes S, Blish CA. Human NK cell repertoire diversity reflects immune experience and correlates with viral susceptibility. Sci Transl Med 2015; 7(297): 297ra115

[98] Kärre K. Natural killer cell recognition of missing self. Nat Immunol 2008; 9(5): 477–480

[99] Glienke J, Sobanov Y, Brostjan C, Steffens C, Nguyen C, Lehrach H, Hofer E, Francis F. The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex. Immunogenetics 1998; 48(3): 163–173

[100] Hatjiharissi E, Xu L, Santos DD, Hunter ZR, Ciccarelli BT, Verselis S, Modica M, Cao Y, Manning RJ, Leleu X, Dimmock EA, Kortsaris A, Mitsiades C, Anderson KC, Fox EA, Treon SP. Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the FcγRIIIa-158 V/V and V/F polymorphism. Blood 2007; 110(7): 2561–2564

[101] Sivori S, Parolini S, Marcenaro E, Millo R, Bottino C, Moretta A. Triggering receptors involved in natural killer cell-mediated cytotoxicity against choriocarcinoma cell lines. Hum Immunol 2000; 61(11): 1055–1058

[102] Hsu HT, Mace EM, Carisey AF, Viswanath DI, Christakou AE, Wiklund M, Önfelt B, Orange JS. NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing. J Cell Biol 2016; 215(6): 875–889

[103] Mace EM, Orange JS. Genetic causes of human NK cell deficiency and their effect on NK cell subsets. Front Immunol 2016; 7: 545

[104] Wong E, Xu RH, Rubio D, Lev A, Stotesbury C, Fang M, Sigal LJ. Migratory dendritic cells, group 1 innate lymphoid cells, and inflammatory monocytes collaborate to recruit NK cells to the virus-infected lymph node. Cell Reports 2018; 24(1): 142–154

[105] Lanier LL. Evolutionary struggles between NK cells and viruses. Nat Rev Immunol 2008; 8(4): 259–268

[106] Raulet DH, Gasser S, Gowen BG, Deng W, Jung H. Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol 2013; 31(1): 413–441

[107] McQuaid S, Loughran S, Power P, Maguire P, Walls D, Cusi MG, Orvell C, Johnson P. Haemagglutinin-neuraminidase from HPIV3 mediates human NK regulation of T cell proliferation via NKp44 and NKp46. J Gen Virol 2018; 99(6): 763–767

[108] Mendelson M, Tekoah Y, Zilka A, Gershoni-Yahalom O, Gazit R, Achdout H, Bovin NV, Meningher T, Mandelboim M, Mandelboim O, David A, Porgador A. NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus. J Virol 2010; 84(8): 3789–3797

[109] Diab M, Glasner A, Isaacson B, Bar-On Y, Drori Y, Yamin R, Duev-Cohen A, Danziger O, Zamostiano R, Mandelboim M, Jonjic S, Bacharach E, Mandelboim O. NK-cell receptors NKp46 and NCR1 control human metapneumovirus infection. Eur J Immunol 2017; 47(4): 692–703

[110] Bar-On Y, Charpak-Amikam Y, Glasner A, Isaacson B, Duev-Cohen A, Tsukerman P, Varvak A, Mandelboim M, Mandelboim O. NKp46 recognizes the sigma1 protein of reovirus: implications for reovirus-based cancer therapy. J Virol 2017; 91(19): e01045-17

[111] Ahlenstiel G, Titerence RH, Koh C, Edlich B, Feld JJ, Rotman Y, Ghany MG, Hoofnagle JH, Liang TJ, Heller T, Rehermann B. Natural killer cells are polarized toward cytotoxicity in chronic hepatitis C in an interferon-α-dependent manner. Gastroenterology 2010; 138: 325–335.e1–2 PMID: 19747917

[112] Béziat V, Dalgard O, Asselah T, Halfon P, Bedossa P, Boudifa A, Hervier B, Theodorou I, Martinot M, Debré P, Björkström NK, Malmberg KJ, Marcellin P, Vieillard V. CMV drives clonal expansion of NKG2C⁺ NK cells expressing self-specific KIRs in chronic hepatitis patients. Eur J Immunol 2012; 42(2): 447–457

[113] Malone DFG, Lunemann S, Hengst J, Ljunggren HG, Manns MP, Sandberg JK, Cornberg M, Wedemeyer H, Björkström NK. Cytomegalovirus-driven adaptive-like natural killer cell expansions are unaffected by concurrent chronic hepatitis virus infections. Front Immunol 2017; 8: 525

[114] Petitdemange C, Wauquier N, Devilliers H, Yssel H, Mombo I, Caron M, Nkoghé D, Debré P, Leroy E, Vieillard V. Longitudinal analysis of natural killer cells in dengue virus-infected patients in comparison to Chikungunya and Chikungunya/Dengue virus-infected patients. PLoS Negl Trop Dis 2016; 10(3): e0004499

[115] Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, González MA, Bernad A, Sánchez-Madrid F. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2011; 2(1): 282

[116] Schorey JS, Harding CV. Extracellular vesicles and infectious diseases: new complexity to an old story. J Clin Invest 2016; 126(4): 1181–1189

[117] Tamai K, Tanaka N, Nakano T, Kakazu E, Kondo Y, Inoue J, Shiina M, Fukushima K, Hoshino T, Sano K, Ueno Y, Shimosegawa T, Sugamura K. Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem Biophys Res Commun 2010; 399(3): 384–390

[118] Kalamvoki M, Deschamps T. Extracellular vesicles during herpes simplex virus type 1 infection: an inquire. Virol J 2016; 13(1): 63

[119] Ratajczak MZ, Ratajczak J. Horizontal transfer of RNA and proteins between cells by extracellular microvesicles: 14 years later. Clin Transl Med 2016; 5(1): 7

[120] Schwab A, Meyering SS, Lepene B, Iordanskiy S, van Hoek ML, Hakami RM, Kashanchi F. Extracellular vesicles from infected cells: potential for direct pathogenesis. Front Microbiol 2015; 6: 1132

[121] Takahashi K, Asabe S, Wieland S, Garaigorta U, Gastaminza P, Isogawa M, Chisari FV. Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection. Proc Natl Acad Sci USA 2010; 107(16): 7431–7436

[122] Dreux M, Garaigorta U, Boyd B, Décembre E, Chung J, Whitten-Bauer C, Wieland S, Chisari FV. Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity. Cell Host Microbe 2012; 12(4): 558–570

[123] Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, Lieberman J. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 2016; 535(7610): 153–158

[124] Lu A, Magupalli VG, Ruan J, Yin Q, Atianand MK, Vos MR, Schröder GF, Fitzgerald KA, Wu H, Egelman EH. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 2014; 156(6): 1193–1206

[125] Balci-Peynircioglu B, Waite AL, Schaner P, Taskiran ZE, Richards N, Orhan D, Gucer S, Ozen S, Gumucio D, Yilmaz E. Expression of ASC in renal tissues of familial mediterranean fever patients with amyloidosis: postulating a role for ASC in AA type amyloid deposition. Exp Biol Med (Maywood) 2008; 233(11): 1324–1333

[126] Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, Barberà-Cremades M, Yagüe J, Ruiz-Ortiz E, Antón J, Buján S, Couillin I, Brough D, Arostegui JI, Pelegrín P. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol 2014; 15(8): 738–748

[127] Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, Brenker C, Nordhoff M, Mirandola SR, Al-Amoudi A, Mangan MS, Zimmer S, Monks BG, Fricke M, Schmidt RE, Espevik T, Jones B, Jarnicki AG, Hansbro PM, Busto P, Marshak-Rothstein A, Hornemann S, Aguzzi A, Kastenmüller W, Latz E. The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation. Nat Immunol 2014; 15(8): 727–737

[128] Chahar HS, Bao X, Casola A. Exosomes and their role in the life cycle and pathogenesis of RNA viruses. Viruses 2015; 7(6): 3204–3225

[129] Birungi G, Chen SM, Loy BP, Ng ML, Li SF. Metabolomics approach for investigation of effects of dengue virus infection using the EA.hy926 cell line. J Proteome Res 2010; 9(12): 6523–6534

[130] Delgado T, Sanchez EL, Camarda R, Lagunoff M. Global metabolic profiling of infection by an oncogenic virus: KSHV induces and requires lipogenesis for survival of latent infection. PLoS Pathog 2012; 8(8): e1002866

[131] Diamond DL, Syder AJ, Jacobs JM, Sorensen CM, Walters KA, Proll SC, McDermott JE, Gritsenko MA, Zhang Q, Zhao R, Metz TO, Camp DG 2nd, Waters KM, Smith RD, Rice CM, Katze MG. Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics. PLoS Pathog 2010; 6(1): e1000719

[132] Fontaine KA, Camarda R, Lagunoff M. Vaccinia virus requires glutamine but not glucose for efficient replication. J Virol 2014; 88(8): 4366–4374

[133] Fontaine KA, Sanchez EL, Camarda R, Lagunoff M. Dengue virus induces and requires glycolysis for optimal replication. J Virol 2015; 89(4): 2358–2366

[134] Ramière C, Rodriguez J, Enache LS, Lotteau V, André P, Diaz O. Activity of hexokinase is increased by its interaction with hepatitis C virus protein NS5A. J Virol 2014; 88(6): 3246–3254

[135] Bandiera S, Pernot S, El Saghire H, Durand SC, Thumann C, Crouchet E, Ye T, Fofana I, Oudot MA, Barths J, Schuster C, Pessaux P, Heim MH, Baumert TF, Zeisel MB. Hepatitis C virus-induced upregulation of microRNA miR-146a-5p in hepatocytes promotes viral infection and deregulates metabolic pathways associated with liver disease pathogenesis. J Virol 2016; 90(14): 6387–6400

[136] Ramani D, De Bandt JP, Cynober L. Aliphatic polyamines in physiology and diseases. Clin Nutr 2014; 33(1): 14–22

[137] Minois N, Carmona-Gutierrez D, Madeo F. Polyamines in aging and disease. Aging (Albany NY) 2011; 3(8): 716–732

[138] Mounce BC, Poirier EZ, Passoni G, Simon-Loriere E, Cesaro T, Prot M, Stapleford KA, Moratorio G, Sakuntabhai A, Levraud JP, Vignuzzi M. Interferon-induced spermidine-spermine acetyltransferase and polyamine depletion restrict Zika and Chikungunya viruses. Cell Host Microbe 2016; 20(2): 167–177

[139] Reiss CS, Komatsu T. Does nitric oxide play a critical role in viral infections? J Virol 1998; 72(6): 4547–4551

[140] Uehara EU, Shida BS, de Brito CA. Role of nitric oxide in immune responses against viruses: beyond microbicidal activity. Inflamm Res 2015; 64(11): 845–852

[141] Colasanti M, Persichini T, Venturini G, Ascenzi P. S-nitrosylation of viral proteins: molecular bases for antiviral effect of nitric oxide. IUBMB Life 1999; 48(1): 25–31

[142] Saura M, Zaragoza C, McMillan A, Quick RA, Hohenadl C, Lowenstein JM, Lowenstein CJ. An antiviral mechanism of nitric oxide: inhibition of a viral protease. Immunity 1999; 10(1): 21–28

[143] Hu J, Mahmoud MI, el-Fakahany EE. Polyamines inhibit nitric oxide synthase in rat cerebellum. Neurosci Lett 1994; 175(1-2): 41–45

[144] Dorhoi A, Yeremeev V, Nouailles G, Weiner J 3rd, Jörg S, Heinemann E, Oberbeck-Müller D, Knaul JK, Vogelzang A, Reece ST, Hahnke K, Mollenkopf HJ, Brinkmann V, Kaufmann SH. Type I IFN signaling triggers immunopathology in tuberculosis-susceptible mice by modulating lung phagocyte dynamics. Eur J Immunol 2014; 44(8): 2380–2393

[145] Watanabe Y, Suzuki O, Haruyama T, Akaike T. Interferon-γ induces reactive oxygen species and endoplasmic reticulum stress at the hepatic apoptosis. J Cell Biochem 2003; 89(2): 244–253

[146] Yim HY, Yang Y, Lim JS, Lee MS, Zhang DE, Kim KI. The mitochondrial pathway and reactive oxygen species are critical contributors to interferon-a/b-mediated apoptosis in Ubp43-deficient hematopoietic cells. Biochem Biophys Res Commun 2012; 423(2): 436–440

[147] Burrack KS, Morrison TE. The role of myeloid cell activation and arginine metabolism in the pathogenesis of virus-induced diseases. Front Immunol 2014; 5: 428

[148] Paschos K, Allday MJ. Epigenetic reprogramming of host genes in viral and microbial pathogenesis. Trends Microbiol 2010; 18(10): 439–447

[149] Ptaschinski C, Mukherjee S, Moore ML, Albert M, Helin K, Kunkel SL, Lukacs NW. RSV-induced H3K4 demethylase KDM5B leads to regulation of dendritic cell-derived innate cytokines and exacerbates pathogenesis in vivo. PLoS Pathog 2015; 11(6): e1004978

[150] Gokhale NS, Horner SM. RNA modifications go viral. PLoS Pathog 2017; 13(3): e1006188

[151] Schliehe C, Flynn EK, Vilagos B, Richson U, Swaminanthan S, Bosnjak B, Bauer L, Kandasamy RK, Griesshammer IM, Kosack L, Schmitz F, Litvak V, Sissons J, Lercher A, Bhattacharya A, Khamina K, Trivett AL, Tessarollo L, Mesteri I, Hladik A, Merkler D, Kubicek S, Knapp S, Epstein MM, Symer DE, Aderem A, Bergthaler A. The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection. Nat Immunol 2015; 16(1): 67–74

[152] Yang J, Tian B, Sun H, Garofalo RP, Brasier AR. Epigenetic silencing of IRF1 dysregulates type III interferon responses to respiratory virus infection in epithelial to mesenchymal transition. Nat Microbiol 2017; 2(8): 17086

[153] Meisel M, Hinterleitner R, Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado GC, Lira SA, Baier G, Chang EB, Eren AM, Weber CR, Busque L, Godley LA, Verdú EF, Barreiro LB, Jabri B. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 2018; 557(7706): 580–584

[154] Zhang Q, Zhao K, Shen Q, Han Y, Gu Y, Li X, Zhao D, Liu Y, Wang C, Zhang X, Su X, Liu J, Ge W, Levine RL, Li N, Cao X. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 2015; 525(7569): 389–393

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Qian Xu, Yuting Tang, and Gang Huang declare no conflict of interest. This manuscript is a review article. It does not involve a research protocol requiring approval by relevant institutional review board or ethics committee.

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