학술논문
Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1
Document Type
article
Author
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
Source
iScience, Vol 25, Iss 7, Pp 104599- (2022)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: 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.