Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1

Nicolas Vabret, Valérie Najburg, Alexander Solovyov, Ramya Gopal, Christopher McClain, Petr Šulc, Sreekumar Balan, Yannis Rahou, Guillaume Beauclair, Maxime Chazal, Hugo Varet, Rachel Legendre, Odile Sismeiro, Raul Y. Sanchez David, Lise Chauveau, Nolwenn Jouvenet, Martin Markowitz, Sylvie van der Werf, Olivier Schwartz, Frédéric TangyNina Bhardwaj, Benjamin D. Greenbaum, Anastassia V. Komarova

Research output: Contribution to journalArticlepeer-review

Abstract

Pattern recognition receptors (PRRs) protect against microbial invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. Although microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation remains overlooked. Here, we characterize the landscape of endogenous ligands that engage RIG-I-like receptors (RLRs) upon infection by different RNA viruses. In each infection, several RNAs transcribed by RNA polymerase III (Pol3) specifically engaged RLRs, particularly the family of Y RNAs. Sensing of Y RNAs was dependent on their mimicking of viral secondary structure and their 5′-triphosphate extremity. Further, we found that HIV-1 triggered a VPR-dependent downregulation of RNA triphosphatase DUSP11 in vitro and in vivo, inducing a transcriptome-wide change of cellular RNA 5′-triphosphorylation that licenses Y RNA immunogenicity. Overall, our work uncovers the contribution of endogenous RNAs to antiviral immunity and demonstrates the importance of this pathway in HIV-1 infection.

Original languageEnglish (US)
Article number104599
JournaliScience
Volume25
Issue number7
DOIs
StatePublished - Jul 15 2022

Keywords

  • Biological sciences
  • Immunology
  • Transcriptomics

ASJC Scopus subject areas

  • General

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