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

Hertzog, J. et al. (2018) Infection with a Brazilian isolate of Zika virus generates RIG‐I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signalling. European Journal of Immunology, 48(7), pp. 1120-1136. (doi:10.1002/eji.201847483) (PMID:29572905) (PMCID:PMC6055886)

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Abstract

Zika virus (ZIKV) is a major public health concern in the Americas. We report that ZIKV infection and RNA extracted from ZIKV infected cells potently activated the induction of type I interferons (IFNs). This effect was fully dependent on the mitochondrial antiviral signalling protein (MAVS), implicating RIG‐I‐like receptors (RLRs) as upstream sensors of viral RNA. Indeed, RIG‐I and the related RNA sensor MDA5 contributed to type I IFN induction in response to RNA from infected cells. We found that ZIKV NS5 from a recent Brazilian isolate blocked type I IFN induction downstream of RLRs and also inhibited type I IFN receptor (IFNAR) signalling. We defined the ZIKV NS5 nuclear localization signal and report that NS5 nuclear localization was not required for inhibition of signalling downstream of IFNAR. Mechanistically, NS5 blocked IFNAR signalling by both leading to reduced levels of STAT2 and by blocking phosphorylation of STAT1, two transcription factors activated by type I IFNs. Taken together, our observations suggest that ZIKV infection induces a type I IFN response via RLRs and that ZIKV interferes with this response by blocking signalling downstream of RLRs and IFNAR.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Donald, Dr Claire and Kohl, Professor Alain
Authors: Hertzog, J., Dias Junior, A. G., Rigby, R. E., Donald, C. L., Mayer, A., Sezgin, E., Song, C., Jin, B., Hublitz, P., Eggeling, C., Kohl, A., and Rehwinkel, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Publisher:Wiley
ISSN:0014-2980
ISSN (Online):1521-4141
Published Online:23 March 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in European Journal of Immunology 48(7): 1120-1136
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH
708681The emergence of Zika virus in Brazil: investigating prevalence and host responses to design preventive strategiesAlain KohlMedical Research Council (MRC)MR/N017552/1MVLS III - CENTRE FOR VIRUS RESEARCH