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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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03707385
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Submitted on : Tuesday, June 28, 2022 - 3:27:54 PM
Last modification on : Friday, August 5, 2022 - 12:03:06 PM

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Y RNAs are conserved endogenou...
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Nicolas Vabret, Valérie Najburg, Alexander Solovyov, Ramya Gopal, Christopher Mcclain, et al.. Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1. iScience, Elsevier, 2022, 25 (7), pp.104599. ⟨10.1016/j.isci.2022.104599⟩. ⟨pasteur-03707385⟩

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