1887

Abstract

Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, , in the family Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5). In this study, by using siRNA knockdown, we report that TV infection in LLC-MK2 cells results in an early [3 h post infection (h p.i.), <0.05] RIG-I-dependent and type I interferon-mediated antiviral response, whereas an MDA5-mediated antiviral effect was observed at later (12 h p.i.; <0.05) stages of TV replication. Induction of RIG-I and MDA5 was critical for inhibition of TV replication. Furthermore, pre-activation of the RIG-I/MDA5 pathway prevented TV replication (>900-fold decrease; <0.05), suggesting that RIG-I and MDA5 ligands could be used to develop novel preventive and therapeutic measures against norovirus.

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2017-05-01
2024-11-12
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References

  1. Radford A, Smith AW, Hansman G, Meyers G, Thiel HJ et al. Caliciviridae Oxford: Elsevier; 2011
    [Google Scholar]
  2. Pringle K, Lopman B, Vega E, Vinje J, Parashar UD et al. Noroviruses: epidemiology, immunity and prospects for prevention. Future Microbiol 2015; 10:53–67 [View Article][PubMed]
    [Google Scholar]
  3. Li J, Predmore A, Divers E, Lou F. New interventions against human norovirus: progress, opportunities, and challenges. Annu Rev Food Sci Technol 2012; 3:331–352 [View Article][PubMed]
    [Google Scholar]
  4. Cromeans T, Park GW, Costantini V, Lee D, Wang Q et al. Comprehensive comparison of cultivable norovirus surrogates in response to different inactivation and disinfection treatments. Appl Environ Microbiol 2014; 80:5743–5751 [View Article][PubMed]
    [Google Scholar]
  5. Farkas T, Sestak K, Wei C, Jiang X. Characterization of a rhesus monkey calicivirus representing a new genus of Caliciviridae. J Virol 2008; 82:5408–5416 [View Article][PubMed]
    [Google Scholar]
  6. Farkas T, Cross RW, Hargitt E, Lerche NW, Morrow AL et al. Genetic diversity and histo-blood group antigen interactions of rhesus enteric caliciviruses. J Virol 2010; 84:8617–8625 [View Article][PubMed]
    [Google Scholar]
  7. Hirneisen KA, Kniel KE. Comparing human norovirus surrogates: murine norovirus and Tulane virus. J Food Prot 2013; 76:139–143 [View Article][PubMed]
    [Google Scholar]
  8. Ranjan P, Bowzard JB, Schwerzmann JW, Jeisy-Scott V, Fujita T et al. Cytoplasmic nucleic acid sensors in antiviral immunity. Trends Mol Med 2009; 15:359–368 [View Article][PubMed]
    [Google Scholar]
  9. Seth RB, Sun L, Chen ZJ. Antiviral innate immunity pathways. Cell Res 2006; 16:141–147 [View Article][PubMed]
    [Google Scholar]
  10. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T et al. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 2008; 205:1601–1610 [View Article][PubMed]
    [Google Scholar]
  11. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004; 5:730–737 [View Article][PubMed]
    [Google Scholar]
  12. Rothenfusser S, Goutagny N, Diperna G, Gong M, Monks BG et al. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol 2005; 175:5260–5268 [View Article][PubMed]
    [Google Scholar]
  13. Bruns AM, Leser GP, Lamb RA, Horvath CM. The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly. Mol Cell 2014; 55:771–781 [View Article][PubMed]
    [Google Scholar]
  14. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 2008; 82:335–345 [View Article][PubMed]
    [Google Scholar]
  15. Gitlin L, Barchet W, Gilfillan S, Cella M, Beutler B et al. Essential role of mda-5 in type I IFN responses to polyriboinosinic: polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci USA 2006; 103:8459–8464 [View Article][PubMed]
    [Google Scholar]
  16. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006; 441:101–105 [View Article][PubMed]
    [Google Scholar]
  17. Sen A, Pruijssers AJ, Dermody TS, García-Sastre A, Greenberg HB. The early interferon response to rotavirus is regulated by PKR and depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3. J Virol 2011; 85:3717–3732 [View Article][PubMed]
    [Google Scholar]
  18. MCcartney SA, Thackray LB, Gitlin L, Gilfillan S, Virgin HW et al. MDA-5 recognition of a murine norovirus. PLoS Pathog 2008; 4:e1000108 [View Article][PubMed]
    [Google Scholar]
  19. Qu L, Murakami K, Broughman JR, Lay MK, Guix S et al. Replication of human norovirus RNA in mammalian cells reveals lack of interferon response. J Virol 2016; 90:8906–8923 [View Article][PubMed]
    [Google Scholar]
  20. Tian J, Zhang X, Wu H, Liu C, Liu J et al. Assessment of the IFN-β response to four feline caliciviruses: infection in CRFK cells. Infect Genet Evol 2015; 34:352–360 [View Article][PubMed]
    [Google Scholar]
  21. Ranjan P, Jayashankar L, Deyde V, Zeng H, Davis WG et al. 5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication. Virol J 2010; 7:102 [View Article][PubMed]
    [Google Scholar]
  22. Miyashita M, Oshiumi H, Matsumoto M, Seya T. DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling. Mol Cell Biol 2011; 31:3802–3819 [View Article]
    [Google Scholar]
  23. Marié I, Durbin JE, Levy DE. Differential viral induction of distinct interferon-α genes by positive feedback through interferon regulatory factor-7. EMBO J 1998; 17:6660–6669 [View Article][PubMed]
    [Google Scholar]
  24. Deonarain R, Alcamí A, Alexiou M, Dallman MJ, Gewert DR et al. Impaired antiviral response and alpha/beta interferon induction in mice lacking beta interferon. J Virol 2000; 74:3404–3409 [View Article][PubMed]
    [Google Scholar]
  25. Paun A, Pitha PM. The IRF family, revisited. Biochimie 2007; 89:744–753 [View Article][PubMed]
    [Google Scholar]
  26. Kell AM, Gale M Jr. RIG-I in RNA virus recognition. Virology 2015; 479-480:110–121 [View Article][PubMed]
    [Google Scholar]
  27. Malathi K, Dong B, Gale M Jr, Silverman RH. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 2007; 448:816–819 [View Article][PubMed]
    [Google Scholar]
  28. Subba-Reddy CV, Goodfellow I, Kao CC. VPg-primed RNA synthesis of norovirus RNA-dependent RNA polymerases by using a novel cell-based assay. J Virol 2011; 85:13027–13037 [View Article][PubMed]
    [Google Scholar]
  29. Weber M, Gawanbacht A, Habjan M, Rang A, Borner C et al. Incoming RNA virus nucleocapsids containing a 5'-triphosphorylated genome activate RIG-I and antiviral signaling. Cell Host Microbe 2013; 13:336–346 [View Article][PubMed]
    [Google Scholar]
  30. Rohayem J, Robel I, Jäger K, Scheffler U, Rudolph W. Protein-primed and de novo initiation of RNA synthesis by norovirus 3Dpol. J Virol 2006; 80:7060–7069 [View Article][PubMed]
    [Google Scholar]
  31. Yu G, Zhang D, Guo F, Tan M, Jiang X et al. Cryo-EM structure of a novel calicivirus, Tulane virus. PLoS One 2013; 8:e59817 [View Article][PubMed]
    [Google Scholar]
  32. Ranjan P, Singh N, Kumar A, Neerincx A, Kremmer E et al. NLRC5 interacts with RIG-I to induce a robust antiviral response against influenza virus infection. Eur J Immunol 2015; 45:758–772 [View Article][PubMed]
    [Google Scholar]
  33. Nikonov A, Mölder T, Sikut R, Kiiver K, Männik A et al. RIG-I and MDA-5 detection of viral RNA-dependent RNA polymerase activity restricts positive-strand RNA virus replication. PLoS Pathog 2013; 9:e1003610 [View Article][PubMed]
    [Google Scholar]
  34. Hüsser L, Alves MP, Ruggli N, Summerfield A. Identification of the role of RIG-I, MDA-5 and TLR3 in sensing RNA viruses in porcine epithelial cells using lentivirus-driven RNA interference. Virus Res 2011; 159:9–16 [View Article][PubMed]
    [Google Scholar]
  35. Nasirudeen AM, Wong HH, Thien P, Xu S, Lam KP et al. RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. PLoS Negl Trop Dis 2011; 5:e926 [View Article][PubMed]
    [Google Scholar]
  36. Xing J, Wang S, Lin R, Mossman KL, Zheng C. Herpes simplex virus 1 tegument protein US11 downmodulates the RLR signaling pathway via direct interaction with RIG-I and MDA-5. J Virol 2012; 86:3528–3540 [View Article][PubMed]
    [Google Scholar]
  37. Jensen S, Thomsen AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol 2012; 86:2900–2910 [View Article][PubMed]
    [Google Scholar]
  38. Spiropoulou CF, Ranjan P, Pearce MB, Sealy TK, Albariño CG et al. RIG-I activation inhibits ebolavirus replication. Virology 2009; 392:11–15 [View Article][PubMed]
    [Google Scholar]
  39. Guo Z, Chen LM, Zeng H, Gomez JA, Plowden J et al. NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I. Am J Respir Cell Mol Biol 2007; 36:263–269 [View Article][PubMed]
    [Google Scholar]
  40. Mcfadden N, Bailey D, Carrara G, Benson A, Chaudhry Y et al. Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4. PLoS Pathog 2011; 7:e1002413 [View Article][PubMed]
    [Google Scholar]
  41. Emmott E, Sorgeloos F, Caddy SL, Vashist S, Sosnovtsev S et al. Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors. Mol Cell Proteomics 2017mcp.M116.062448 [View Article][PubMed]
    [Google Scholar]
  42. Böttcher E, Freuer C, Steinmetzer T, Klenk HD, Garten W. MDCK cells that express proteases TMPRSS2 and HAT provide a cell system to propagate influenza viruses in the absence of trypsin and to study cleavage of HA and its inhibition. Vaccine 2009; 27:6324–6329 [View Article][PubMed]
    [Google Scholar]
  43. Sestak K, Feely S, Fey B, Dufour J, Hargitt E et al. Experimental inoculation of juvenile rhesus macaques with primate enteric caliciviruses. PLoS One 2012; 7:e37973 [View Article][PubMed]
    [Google Scholar]
  44. Wang Y, Ludwig J, Schuberth C, Goldeck M, Schlee M et al. Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I. Nat Struct Mol Biol 2010; 17:781–787 [View Article][PubMed]
    [Google Scholar]
  45. Guix S, Asanaka M, Katayama K, Crawford SE, Neill FH et al. Norwalk virus RNA is infectious in mammalian cells. J Virol 2007; 81:12238–12248 [View Article][PubMed]
    [Google Scholar]
  46. Mumphrey SM, Changotra H, Moore TN, Heimann-Nichols ER, Wobus CE et al. Murine norovirus 1 infection is associated with histopathological changes in immunocompetent hosts, but clinical disease is prevented by STAT1-dependent interferon responses. J Virol 2007; 81:3251–3263 [View Article][PubMed]
    [Google Scholar]
  47. Karst SM, Wobus CE, Lay M, Davidson J, Virgin HW. STAT1-dependent innate immunity to a Norwalk-like virus. Science 2003; 299:1575–1578 [View Article][PubMed]
    [Google Scholar]
  48. Hosmillo M, Sorgeloos F, Hiraide R, Lu J, Goodfellow I et al. Porcine sapovirus replication is restricted by the type I interferon response in cell culture. J Gen Virol 2015; 96:74–84 [View Article][PubMed]
    [Google Scholar]
  49. Ohe K, Takahashi T, Hara D, Hara M. Sensitivity of FCV to recombinant feline interferon (rFeIFN). Vet Res Commun 2008; 32:167–174 [View Article][PubMed]
    [Google Scholar]
  50. Jones MK, Grau KR, Costantini V, Kolawole AO, de Graaf M et al. Human norovirus culture in B cells. Nat Protoc 2015; 10:1939–1947 [View Article][PubMed]
    [Google Scholar]
  51. Ettayebi K, Crawford SE, Murakami K, Broughman JR, Karandikar U et al. Replication of human noroviruses in stem cell-derived human enteroids. Science 2016; 353:1387–1393 [View Article][PubMed]
    [Google Scholar]
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