Aedes aegypti Piwi4 is a noncanonical PIWI protein involved in antiviral responses

Varjak, M. et al. (2017) Aedes aegypti Piwi4 is a noncanonical PIWI protein involved in antiviral responses. mSphere, 2(3), 00144-17. (doi: 10.1128/mSphere.00144-17) (PMID:28497119) (PMCID:PMC5415634)

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The small interfering RNA (siRNA) pathway is a major antiviral response in mosquitoes; however, another RNA interference pathway, the PIWI-interacting RNA (piRNA) pathway, has been suggested to be antiviral in mosquitoes. Piwi4 has been reported to be a key mediator of this response in mosquitoes, but it is not involved in the production of virus-specific piRNAs. Here, we show that Piwi4 associates with members of the antiviral exogenous siRNA pathway (Ago2 and Dcr2), as well as with proteins of the piRNA pathway (Ago3, Piwi5, and Piwi6) in an Aedes aegypti-derived cell line, Aag2. Analysis of small RNAs captured by Piwi4 revealed that it is predominantly associated with virus-specific siRNAs in Semliki Forest virus-infected cells and, to a lesser extent, with viral piRNAs. By using a Dcr2 knockout cell line, we showed directly that Ago2 lost its antiviral activity, as it was no longer bound to siRNAs, but Piwi4 retained its antiviral activity in the absence of the siRNA pathway. These results demonstrate a complex interaction between the siRNA and piRNA pathways in A. aegypti and identify Piwi4 as a noncanonical PIWI protein that interacts with members of the siRNA and piRNA pathways, and its antiviral activities may be independent of either pathway.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Donald, Dr Claire and Kean, Dr Joy and Sterk, Mr Jelle and Vattipally, Dr Sreenu and Schnettler, Dr Esther and Varjak, Dr Margus and Pondeville, Dr Emilie and Kohl, Professor Alain
Authors: Varjak, M., Maringer, K., Watson, M., Sreenu, V., Fredericks, A. C., Pondeville, E., Kohl, A., Sterk, J., Kean, J., Vazeille, M., Failloux, A.-B., Donald, C. L., and Schnettler, E.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:mSphere
Publisher:American Society for Microbiology
ISSN (Online):2379-5042
Published Online:03 May 2017
Copyright Holders:Copyright © 2017 Varjak et al.
First Published:First published in mSphere 2(3):00144-17
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH
698111MAPPAlain KohlEuropean Commission (EC)661232MVLS III - CENTRE FOR VIRUS RESEARCH