Argonaute 2 targets viral transcripts but not genomes of RNA viruses during antiviral RNA interference in Drosophila
RNA interference (RNAi) mediated by the small interfering RNA (siRNA) pathway is a major antiviral mechanism in insects. This pathway is triggered when double-stranded RNA (dsRNA) produced during virus replication is recognized by Dicer-2, leading to the formation of virus-derived siRNA duplexes. These siRNAs are loaded onto the programmable nuclease Argonaute-2 (AGO2), with one strand serving as a guide to target and cleave fully complementary sequences of viral RNAs. While siRNAs are generated from viral dsRNA, the specific viral RNA species targeted for silencing during RNA virus replication remains unclear. In this study, we characterized the primary viral RNA targets of the Drosophila siRNA pathway during infections caused by negative and positive RNA viruses, namely Vesicular stomatitis virus (VSV) and Sindbis virus (SINV). Our findings reveal that polyadenylated transcripts of VSV and SINV are the major targets of silencing by the siRNA pathway during infection, likely when they are poised for translation. Consistent with earlier findings, we show that AGO2 is associated with ribosomes in control and virus infected cells. Therefore, we propose that the inhibition of the replication of RNA viruses in Drosophila results from the silencing of incoming viral transcripts, facilitated by the association of AGO2 with ribosomes.
Authors
- Carine Meignin (ORCID: https://orcid.org/0000-0002-6588-9045)
- Carlos F. Estevez-Castro (ORCID: https://orcid.org/0000-0002-9872-2006)
- Karim Majzoub (ORCID: https://orcid.org/0000-0001-7345-6840)
- Joëlle Vinh (ORCID: https://orcid.org/0000-0001-7184-2668)
- Gabrielle Haas
- Emanuele Guimarães Silva
- Yann Verdier (ORCID: https://orcid.org/0000-0002-3319-0053)
- João T. Marques (ORCID: https://orcid.org/0000-0002-3457-3320)
- Siad C. G. Amadou (ORCID: https://orcid.org/0000-0001-6508-0361)
- Isaque J. S. de Faria (ORCID: https://orcid.org/0000-0002-8810-8133)
- Juliana N. Armache (ORCID: https://orcid.org/0000-0003-4274-8562)
- Franck Martin (ORCID: https://orcid.org/0000-0001-9724-4025)
- Álvaro Ferreira (ORCID: https://orcid.org/0000-0002-6299-0391)
- Thiago Henrique L. Jiran
- Jean-Luc Imler
Institutions
- Universidade Federal de Minas Gerais (BR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- ParisTech (FR)
- Université de Montpellier (FR)
- Institut de Génétique Moléculaire de Montpellier (FR)
- Université de Strasbourg (FR)
- ESPCI Paris (FR)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2025-02-03
- DOI
- https://doi.org/10.1371/journal.ppat.1012184
- Citations
- 1
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Fundo Regional para a Ciência e Tecnologia
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Université de Strasbourg
- Centre National de la Recherche Scientifique
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais