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

Olson, Ken E., Varjak, Margus, Donald, Claire L., Mottram, Timothy J., Sreenu, Vattipally B., Merits, Andres, Maringer, Kevin, Schnettler, Esther and Kohl, Alain (2017) Characterization of the Zika virus induced small RNA response in Aedes aegypti cells PLOS Neglected Tropical Diseases, 11 (10).

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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: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Olson, Ken E.
Varjak, Margus
Donald, Claire L.
Mottram, Timothy J.
Sreenu, Vattipally B.
Merits, Andres
Maringer, Kevink.maringer@surrey.ac.uk
Schnettler, Esther
Kohl, Alain
Date : 17 October 2017
Funders : Medical Research Council (MRC)
Identification Number : 10.1371/journal.pntd.0006010
Copyright Disclaimer : © 2017 Varjak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Clive Harris
Date Deposited : 18 Oct 2017 14:36
Last Modified : 14 Mar 2018 13:35
URI: http://epubs.surrey.ac.uk/id/eprint/842569

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