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

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 P...

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Published in:iScience Vol. 25; no. 7; p. 104599
Main Authors: Vabret, Nicolas, Najburg, Valérie, Solovyov, Alexander, Gopal, Ramya, McClain, Christopher, Šulc, Petr, Balan, Sreekumar, Rahou, Yannis, Beauclair, Guillaume, Chazal, Maxime, Varet, Hugo, Legendre, Rachel, Sismeiro, Odile, Sanchez David, Raul Y., Chauveau, Lise, Jouvenet, Nolwenn, Markowitz, Martin, van der Werf, Sylvie, Schwartz, Olivier, Tangy, Frédéric, Bhardwaj, Nina, Greenbaum, Benjamin D., Komarova, Anastassia V.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 15.07.2022
Elsevier
Subjects:
Biological sciences
Immunology
Life Sciences
Transcriptomics
Transcriptomics
Biological sciences
Immunology
ISSN:2589-0042, 2589-0042
Online Access:Get full text
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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. [Display omitted] •Y RNAs and other POL3 transcripts are RLRs ligands during RNA virus infections•Y RNA immunogenicity depends on their 5′-PPP and viral-mimicry secondary structure•Development of a novel sequencing approach to measure 5′-PPP status of RNA•HIV-1 VPR triggers DUSP11 downregulation and modulates host 5′-PPP transcriptome Biological sciences; Immunology; Transcriptomics
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.104599