Retroviral GAG proteins recruit AGO2 on viral RNAs without affecting RNA accumulation and translation

Manuella Bouttier (1) , Anne Saumet (2) , Marion Peter (1) , Valérie Courgnaud (3) , Ute Schmidt (1) , Chantal Cazevieille (4) , Edouard Bertrand (1) , Charles-Henri Lecellier (1)

1 IGMM - Institut de Génétique Moléculaire de Montpellier
2 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier
3 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
4 Centre de Ressources en Imagerie Cellulaire CRIC/IURC

Cellular micro(mi)RNAs are able to recognize viral RNAs through imperfect micro-homologies. Similar to the miRNA-mediated repression of cellular translation, this recognition is thought to tether the RNAi machinery, in particular Argonaute 2 (AGO2) on viral messengers and eventually to modulate virus replication. Here, we unveil another pathway by which AGO2 can interact with retroviral mRNAs. We show that AGO2 interacts with the retroviral Group Specific Antigen (GAG) core proteins and preferentially binds unspliced RNAs through the RNA packaging sequences without affecting RNA stability or eliciting translation repression. Using RNAi experiments, we provide evidences that these interactions, observed with both the human immunodeficiency virus 1 (HIV-1) and the primate foamy virus 1 (PFV-1), are required for retroviral replication. Taken together, our results place AGO2 at the core of the retroviral life cycle and reveal original AGO2 functions that are not related to miRNAs and translation repression.

Domaines: Virologie; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Manuella Bouttier, Anne Saumet, Marion Peter, Valérie Courgnaud, Ute Schmidt, et al.. Retroviral GAG proteins recruit AGO2 on viral RNAs without affecting RNA accumulation and translation. Nucleic Acids Research, 2012, 40 (2), pp.775-786. ⟨10.1093/nar/gkr762⟩. ⟨hal-02106456⟩