Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral Responses

Abstract : 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. IMPORTANCE Mosquitoes transmit several pathogenic viruses, for example, the chikungunya and Zika viruses. In mosquito cells, virus replication intermediates in the form of double-stranded RNA are cleaved by Dcr2 into 21-nucleotide-long siRNAs, which in turn are used by Ago2 to target the virus genome. A different class of virus-derived small RNAs, PIWI-interacting RNAs (piRNAs), have also been found in infected insect cells. These piRNAs are longer and are produced in a Dcr2-independent manner. The only known antiviral protein in the PIWI family is Piwi4, which is not involved in piRNA production. It is associated with key proteins of the siRNA and piRNA pathways, although its antiviral function is independent of their actions.
Type de document :
Article dans une revue
MSphere, American Society for Microbiology., 2017, 2 (3), pp.e00144-17. 〈10.1128/mSphere.00144-17〉
Liste complète des métadonnées

Littérature citée [47 références]  Voir  Masquer  Télécharger

https://hal-pasteur.archives-ouvertes.fr/pasteur-01573771
Contributeur : Marie Demeslay Gougam <>
Soumis le : jeudi 10 août 2017 - 15:21:15
Dernière modification le : mercredi 7 mars 2018 - 10:26:02

Fichier

e00144-17.full.pdf
Publication financée par une institution

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Collections

Citation

Margus Varjak, Kevin Maringer, Mick Watson, Vattipally B. Sreenu, Anthony C. Fredericks, et al.. Aedes aegypti Piwi4 Is a Noncanonical PIWI Protein Involved in Antiviral Responses. MSphere, American Society for Microbiology., 2017, 2 (3), pp.e00144-17. 〈10.1128/mSphere.00144-17〉. 〈pasteur-01573771〉

Partager

Métriques

Consultations de la notice

43

Téléchargements de fichiers

47