Characterization of the Zika virus induced small RNA response in Aedes aegypti cells

Varjak, M. , Donald, C. L. , Mottram, T. J., Sreenu, V. B. , Merits, A., Maringer, K., Schnettler, E. and Kohl, A. (2017) Characterization of the Zika virus induced small RNA response in Aedes aegypti cells. PLoS Neglected Tropical Diseases, 11(10), e0006010. (doi:10.1371/journal.pntd.0006010) (PMID:29040304) (PMCID:PMC5667879)

Varjak, M. , Donald, C. L. , Mottram, T. J., Sreenu, V. B. , Merits, A., Maringer, K., Schnettler, E. and Kohl, A. (2017) Characterization of the Zika virus induced small RNA response in Aedes aegypti cells. PLoS Neglected Tropical Diseases, 11(10), e0006010. (doi:10.1371/journal.pntd.0006010) (PMID:29040304) (PMCID:PMC5667879)

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Abstract

RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25–29 and 21 nucleotides, respectively. The exo-siRNA pathway is considered to be the key mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not enhance virus replication. Enhanced ZIKV replication was observed in a Dcr2-knockout cell line suggesting that the exo-siRNA pathway is implicated in the antiviral response. Although ZIKV-specific piRNA-sized small RNAs were detected, these lacked the characteristic piRNA ping-pong signature motif and were bound to Ago3 but not Piwi5 or Piwi6. Silencing of PIWI proteins indicated that the knockdown of Ago3, Piwi5 or Piwi6 did not enhance ZIKV replication and only Piwi4 displayed antiviral activity. We also report that the expression of ZIKV capsid (C) protein amplified the replication of a reporter alphavirus; although, unlike yellow fever virus C protein, it does not inhibit the exo-siRNA pathway. Our findings elucidate ZIKV-mosquito RNAi interactions that are important for understanding its spread.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Schnettler, Dr Esther and Mottram, Mr Timothy and Varjak, Dr Margus and Vattipally, Dr Sreenu and Donald, Dr Claire and Kohl, Professor Alain
Authors: Varjak, M., Donald, C. L., Mottram, T. J., Sreenu, V. B., Merits, A., Maringer, K., Schnettler, E., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2017 Varjak et al.
First Published:First published in PLoS Neglected Tropical Diseases 11(10): e0006010
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
737371ZikallianceAlain KohlEuropean Commission (EC)734548MVLS III - CENTRE FOR VIRUS RESEARCH