Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1 Journal Article
| Authors: | Vabret, N.; Najburg, V.; Solovyov, A.; Gopal, R.; McClain, C.; Šulc, P.; Balan, S.; Rahou, Y.; Beauclair, G.; Chazal, M.; Varet, H.; Legendre, R.; Sismeiro, O.; Sanchez David, R. Y.; Chauveau, L.; Jouvenet, N.; Markowitz, M.; van der Werf, S.; Schwartz, O.; Tangy, F.; Bhardwaj, N.; Greenbaum, B. D.; Komarova, A. V. |
| Article Title: | 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. © 2022 The Authors |
| Keywords: | transcriptomics; immunology; biological sciences |
| Journal Title: | iScience |
| Volume: | 25 |
| Issue: | 7 |
| ISSN: | 2589-0042 |
| Publisher: | Cell Press |
| Date Published: | 2022-07-15 |
| Start Page: | 104599 |
| Language: | English |
| DOI: | 10.1016/j.isci.2022.104599 |
| PROVIDER: | scopus |
| PMCID: | PMC9250025 |
| PUBMED: | 35789859 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
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