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

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.

• Authors: 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 Tangy, Nina Bhardwaj, Benjamin D Greenbaum, Anastassia V Komarova
• Journal: iScience (iScience) Vol. 25 Issue 7 Pg. 104599 (Jul 15 2022) ISSN: 2589-0042 [Electronic] United States
• PMID: 35789859 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors.