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Scientific Fields
Diseases
Organisms
Applications
Technique

Published in iScience - 15 Jul 2022

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 RY, Chauveau L, Jouvenet N, Markowitz M, van der Werf S, Schwartz O, Tangy F, Bhardwaj N, Greenbaum BD, Komarova AV,

Link to Pubmed [PMID] – 35789859

Link to DOI – 10.1016/j.isci.2022.104599

iScience 2022 Jul; 25(7): 104599

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.

https://pubmed.ncbi.nlm.nih.gov/35789859