Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signaling

European Journal of Immunology

Volumn 48, Issue 7, 2018, Pages 1120-1136

  Hertzog, Jonny ^a   Dias Junior, Antonio Gregorio ^a   Rigby, Rachel E ^a   Donald, Claire L ^b   Mayer, Alice ^a   Sezgin, Erdinc ^a   Song, Chaojun ^c   Jin, Boquan ^c   Hublitz, Philip ^a   Eggeling, Christian ^a   Kohl, Alain ^b   Rehwinkel, Jan ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b MRC UNIVERSITY OF GLASGOW CENTRE FOR VIRUS RESEARCH   (United Kingdom)

^c FOURTH MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Interferon; MDA5; RIG I; STAT; Zika virus

Indexed keywords

INTERFERON; INTERFERON INDUCED HELICASE C DOMAIN CONTAINING PROTEIN 1; INTERFERON RECEPTOR; MESSENGER RNA; NONSTRUCTURAL PROTEIN 5; RETINOIC ACID INDUCIBLE PROTEIN I; RNA POLYMERASE; STAT1 PROTEIN; STAT2 PROTEIN; VIRUS RNA; DDX58 PROTEIN, HUMAN; NS5 PROTEIN, FLAVIVIRUS; RNA; VIRAL PROTEIN;

A-549 CELL LINE; ARTICLE; BRAZIL; CELL STIMULATION; CONTROLLED STUDY; DENSITOMETRY; HEK293 CELL LINE; HUMAN; HUMAN TISSUE; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSIENT TRANSFECTION; ZIKA FEVER; DOWN REGULATION; GENETICS; IMMUNOLOGY; METABOLISM; NUCLEOCYTOPLASMIC TRANSPORT; PHOSPHORYLATION; VIRUS REPLICATION; ZIKA VIRUS;

ACTIVE TRANSPORT, CELL NUCLEUS; BRAZIL; DEAD BOX PROTEIN 58; DOWN-REGULATION; HEK293 CELLS; HUMANS; INTERFERON TYPE I; PHOSPHORYLATION; RNA; SIGNAL TRANSDUCTION; STAT1 TRANSCRIPTION FACTOR; STAT2 TRANSCRIPTION FACTOR; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION; ZIKA VIRUS; ZIKA VIRUS INFECTION;

EID: 85044844141     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201847483     Document Type: Article

References (63)

1. Dick, G. W., Kitchen, S. F. and Haddow, A. J., Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 1952. 46: 509–520.
2. Dick, G. W., Zika virus. II. Pathogenicity and physical properties. Trans R Soc Trop Med Hyg 1952. 46: 521–534.
3. Faria, N. R., Azevedo Rdo, S., Kraemer, M. U., Souza, R., Cunha, M. S., Hill, S. C., Theze, J. et al., Zika virus in the Americas: Early epidemiological and genetic findings. Science 2016. 352: 345–349.
4. Zhu, Z., Chan, J. F., Tee, K. M., Choi, G. K., Lau, S. K., Woo, P. C., Tse, H. et al., Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic. Emerg Microbes Infect 2016. 5: e22.
5. Fajardo, A., Cristina, J. and Moreno, P., Emergence and spreading potential of Zika virus. Front Microbiol 2016. 7: 1667.
6. Sakkas, H., Economou, V. and Papadopoulou, C., Zika virus infection: past and present of another emerging vector-borne disease. J Vector Borne Dis 2016. 53: 305–311.
7. Li, H., Saucedo-Cuevas, L., Shresta, S. and Gleeson, J. G., The neurobiology of Zika virus. Neuron 2016. 92: 949–958.
8. Hamer, D. H., Wilson, M. E., Jean, J. and Chen, L. H., Epidemiology, prevention, and potential future treatments of sexually transmitted Zika virus infection. Curr Infect Dis Rep 2017. 19: 16.
9. Song, B. H., Yun, S. I., Woolley, M. and Lee, Y. M., Zika virus: history, epidemiology, transmission, and clinical presentation. J Neuroimmunol 2017. 308: 50–64.
10. Vasilakis, N. and Weaver, S. C., Flavivirus transmission focusing on Zika. Curr Opin Virol 2017. 22: 30–35.
11. Mlakar, J., Korva, M., Tul, N., Popovic, M., Poljsak-Prijatelj, M., Mraz, J., Kolenc, M. et al., Zika virus associated with microcephaly. N Engl J Med 2016. 374: 951–958.
12. McNab, F., Mayer-Barber, K., Sher, A., Wack, A. and O'Garra, A., Type I interferons in infectious disease. Nat Rev Immunol 2015. 15: 87–103.
13. Hartmann, G., Nucleic acid immunity. Adv Immunol 2017. 133: 121–169.
14. Barrat, F. J., Elkon, K. B. and Fitzgerald, K. A., Importance of nucleic acid recognition in inflammation and autoimmunity. Annu Rev Med 2016. 67: 323–336.
15. Rehwinkel, J. and Reis e Sousa, C., Targeting the viral Achilles' heel: recognition of 5'-triphosphate RNA in innate anti-viral defence. Curr Opin Microbiol 2013. 16: 485–492.
16. Goubau, D., Schlee, M., Deddouche, S., Pruijssers, A. J., Zillinger, T., Goldeck, M., Schuberth, C. et al., Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates. Nature 2014. 514: 372–375.
17. Schoggins, J. W., Wilson, S. J., Panis, M., Murphy, M. Y., Jones, C. T., Bieniasz, P. and Rice, C. M., A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 2011. 472: 481–485.
18. Hamel, R., Dejarnac, O., Wichit, S., Ekchariyawat, P., Neyret, A., Luplertlop, N., Perera-Lecoin, M. et al., Biology of Zika virus infection in human skin cells. J Virol 2015. 89: 8880–8896.
19. Kumar, A., Hou, S., Airo, A. M., Limonta, D., Mancinelli, V., Branton, W., Power, C. et al., Zika virus inhibits type-I interferon production and downstream signaling. EMBO Rep 2016. 17: 1766–1775.
20. Govero, J., Esakky, P., Scheaffer, S. M., Fernandez, E., Drury, A., Platt, D. J., Gorman, M. J. et al., Zika virus infection damages the testes in mice. Nature 2016. 540: 438–442.
21. Lazear, H. M., Govero, J., Smith, A. M., Platt, D. J., Fernandez, E., Miner, J. J. and Diamond, M. S., A mouse model of zika virus pathogenesis. Cell Host Microbe 2016. 19: 720–730.
22. Miner, J. J., Cao, B., Govero, J., Smith, A. M., Fernandez, E., Cabrera, O. H., Garber, C. et al., Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell 2016. 165: 1081–1091.
23. Yockey, L. J., Varela, L., Rakib, T., Khoury-Hanold, W., Fink, S. L., Stutz, B., Szigeti-Buck, K. et al., Vaginal exposure to Zika virus during pregnancy leads to fetal brain infection. Cell 2016. 166: 1247–1256.e1244.
24. Ma, W., Li, S., Ma, S., Jia, L., Zhang, F., Zhang, Y., Zhang, J. et al., Zika virus causes testis damage and leads to male infertility in mice. Cell 2017. 168: 542.
25. Tripathi, S., Balasubramaniam, V. R., Brown, J. A., Mena, I., Grant, A., Bardina, S. V., Maringer, K. et al., A novel Zika virus mouse model reveals strain specific differences in virus pathogenesis and host inflammatory immune responses. PLoS Pathog 2017. 13: e1006258.
26. Winkler, C. W., Myers, L. M., Woods, T. A., Messer, R. J., Carmody, A. B., McNally, K. L., Scott, D. P. et al., Adaptive immune responses to Zika virus are important for controlling virus infection and preventing infection in brain and testes. J Immunol 2017. 198: 3526–3535.
27. Bowen, J. R., Quicke, K. M., Maddur, M. S., O'Neal, J. T., McDonald, C. E., Fedorova, N. B., Puri, V. et al., Zika virus antagonizes Type I interferon responses during infection of human dendritic cells. PLoS Pathog 2017. 13: e1006164.
28. Grant, A., Ponia, S. S., Tripathi, S., Balasubramaniam, V., Miorin, L., Sourisseau, M., Schwarz, M. C. et al., Zika virus targets human STAT2 to inhibit Type I interferon signaling. Cell Host Microbe 2016. 19: 882–890.
29. Smith, D. R., Sprague, T. R., Hollidge, B. S., Valdez, S. M., Padilla, S. L., Bellanca, S. A., Golden, J. W. et al., African and Asian Zika virus isolates display phenotypic differences both in vitro and in vivo. Am J Trop Med Hyg 2017. 98: 432–444.
30. Xia, H., Luo, H., Shan, C., Muruato, A. E., Nunes, B. T. D., Medeiros, D. B. A., Zou, J. et al., An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. Nat Commun 2018. 9: 414.
31. Rehwinkel, J., Tan, C. P., Goubau, D., Schulz, O., Pichlmair, A., Bier, K., Robb, N. et al., RIG-I detects viral genomic RNA during negative-strand RNA virus infection. Cell 2010. 140: 397–408.
32. Pichlmair, A., Schulz, O., Tan, C. P., Rehwinkel, J., Kato, H., Takeuchi, O., Akira, S. et al., Activation of MDA5 requires higher-order RNA structures generated during virus infection. J Virol 2009. 83: 10761–10769.
33. Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S. et al., Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006. 441: 101–105.
34. Donald, C. L., Brennan, B., Cumberworth, S. L., Rezelj, V. V., Clark, J. J., Cordeiro, M. T., Freitas de Oliveira Franca, R. et al., Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil. PLoS Negl Trop Dis 2016. 10: e0005048.
35. Hato, S. V., Ricour, C., Schulte, B. M., Lanke, K. H., de Bruijni, M., Zoll, J., Melchers, W. J. et al., The mengovirus leader protein blocks interferon-alpha/beta gene transcription and inhibits activation of interferon regulatory factor 3. Cell Microbiol 2007. 9: 2921–2930.
36. Bridgeman, A., Maelfait, J., Davenne, T., Partridge, T., Peng, Y., Mayer, A., Dong, T. et al., Viruses transfer the antiviral second messenger cGAMP between cells. Science 2015. 349: 1228–1232.
37. Wang, C., Yang, S. N. Y., Smith, K., Forwood, J. K. and Jans, D. A., Nuclear import inhibitor N-(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection. Biochem Biophys Res Commun 2017. 493: 1555–1559.
38. Hou, W., Cruz-Cosme, R., Armstrong, N., Obwolo, L. A., Wen, F., Hu, W., Luo, M. H. et al., Molecular cloning and characterization of the genes encoding the proteins of Zika virus. Gene 2017. 628: 117–128.
39. Mutso, M., Saul, S., Rausalu, K., Susova, O., Zusinaite, E., Mahalingam, S. and Merits, A., Reverse genetic system, genetically stable reporter viruses and packaged subgenomic replicon based on a Brazilian Zika virus isolate. J Gen Virol 2017. 98: 2712–2724.
40. Brooks, A. J., Johansson, M., John, A. V., Xu, Y., Jans, D. A. and Vasudevan, S. G., The interdomain region of dengue NS5 protein that binds to the viral helicase NS3 contains independently functional importin beta 1 and importin alpha/beta-recognized nuclear localization signals. J Biol Chem 2002. 277: 36399–36407.
41. Pryor, M. J., Rawlinson, S. M., Butcher, R. E., Barton, C. L., Waterhouse, T. A., Vasudevan, S. G., Bardin, P. G. et al., Nuclear localization of dengue virus nonstructural protein 5 through its importin alpha/beta-recognized nuclear localization sequences is integral to viral infection. Traffic 2007. 8: 795–807.
42. Ray, D., Shah, A., Tilgner, M., Guo, Y., Zhao, Y., Dong, H., Deas, T. S. et al., West Nile virus 5'-cap structure is formed by sequential guanine N-7 and ribose 2'-O methylations by nonstructural protein 5. J Virol 2006. 80: 8362–8370.
43. Zhou, Y., Ray, D., Zhao, Y., Dong, H., Ren, S., Li, Z., Guo, Y. et al., Structure and function of flavivirus NS5 methyltransferase. J Virol 2007. 81: 3891–3903.
44. Hyman, A. A., Weber, C. A. and Julicher, F., Liquid-liquid phase separation in biology. Annu Rev Cell Dev Biol 2014. 30: 39–58.
45. Klema, V. J., Padmanabhan, R. and Choi, K. H., Flaviviral replication complex: coordination between RNA synthesis and 5'-RNA capping. Viruses 2015. 7: 4640–4656.
46. Cortese, M., Goellner, S., Acosta, E. G., Neufeldt, C. J., Oleksiuk, O., Lampe, M., Haselmann, U. et al., Ultrastructural characterization of Zika virus replication factories. Cell Rep 2017. 18: 2113–2123.
47. Zeng, W., Sun, L., Jiang, X., Chen, X., Hou, F., Adhikari, A., Xu, M. et al., Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 2010. 141: 315–330.
48. Cao, X., Ding, Q., Lu, J., Tao, W., Huang, B., Zhao, Y., Niu, J. et al., MDA5 plays a critical role in interferon response during hepatitis C virus infection. J Hepatol 2015. 62: 771–778.
49. Garcia-Sastre, A., Ten strategies of interferon evasion by viruses. Cell Host Microbe 2017. 22: 176–184.
50. Best, S. M., The many faces of the flavivirus NS5 protein in antagonism of type I interferon signaling. J Virol 2017. 91: e01970-16.
51. Cumberworth, S. L., Clark, J. J., Kohl, A. and Donald, C. L., Inhibition of type I interferon induction and signaling by mosquito-borne flaviviruses. Cell Microbiol 2017. 19: e12737.
52. Van der Hoek, K. H., Eyre, N. S., Shue, B., Khantisitthiporn, O., Glab-Ampi, K., Carr, J. M., Gartner, M. J. et al., Viperin is an important host restriction factor in control of Zika virus infection. Sci Rep 2017. 7: 4475.
53. Wu, Y., Liu, Q., Zhou, J., Xie, W., Chen, C., Wang, Z., Yang, H. et al., Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro. Cell Discovery 2017. 3: 17006.
54. Lopez-Denman, A. J. and Mackenzie, J. M., The importance of the nucleus during flavivirus replication. Viruses 2017. 9: 14.
55. De Maio, F. A., Risso, G., Iglesias, N. G., Shah, P., Pozzi, B., Gebhard, L. G., Mammi, P. et al., The dengue virus NS5 protein intrudes in the cellular spliceosome and modulates splicing. PLoS Pathog 2016. 12: e1005841.
56. Marzahn, M. R., Marada, S., Lee, J., Nourse, A., Kenrick, S., Zhao, H., Ben-Nissan, G. et al., Higher-order oligomerization promotes localization of SPOP to liquid nuclear speckles. Embo j 2016. 35: 1254–1275.
57. Saha, S., Weber, C. A., Nousch, M., Adame-Arana, O., Hoege, C., Hein, M. Y., Osborne-Nishimura, E. et al., Polar positioning of phase-separated liquid compartments in cells regulated by an mRNA competition mechanism. Cell 2016. 166: 1572–1584.e1516.
58. Banani, S. F., Lee, H. O., Hyman, A. A. and Rosen, M. K., Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 2017. 18: 285–298.
59. Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K. 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.
60. Kuno, G. and Chang, G. J., Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch Virol 2007. 152: 687–696.
61. Brubaker, S. W., Gauthier, A. E., Mills, E. W., Ingolia, N. T. and Kagan, J. C., A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity. Cell 2014. 156: 800–811.
62. Brinkman, E. K., Chen, T., Amendola, M. and van Steensel, B., Easy quantitative assessment of genome editing by sequence trace decomposition. Nucleic Acids Res 2014. 42: e168.
63. Schneider, C. A., Rasband, W. S. and Eliceiri, K. W., NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012. 9: 671–675.