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

Autor: Vabret N; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Najburg V; Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Solovyov A; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Gopal R; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., McClain C; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Šulc P; Center for Molecular Design and Biomimetics at the Biodesign Institute and School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA., Balan S; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Rahou Y; Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Beauclair G; Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Chazal M; Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Varet H; Transcriptome and EpiGenome Platform, BioMics, Center of Innovation and Technological Research, Institut Pasteur, Université de Paris, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.; Hub Informatique et Biostatistique, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI, USR 3756 IP-CNRS), Institut Pasteur, Université de Paris, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France., Legendre R; Transcriptome and EpiGenome Platform, BioMics, Center of Innovation and Technological Research, Institut Pasteur, Université de Paris, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.; Hub Informatique et Biostatistique, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI, USR 3756 IP-CNRS), Institut Pasteur, Université de Paris, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France., Sismeiro O; Transcriptome and EpiGenome Platform, BioMics, Center of Innovation and Technological Research, Institut Pasteur, Université de Paris, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France., Sanchez David RY; Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Chauveau L; Virus & Immunity Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Jouvenet N; Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Markowitz M; Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY, USA., van der Werf S; Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Schwartz O; Virus & Immunity Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Tangy F; Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France., Bhardwaj N; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Extra-mural Member, Parker Institute of Cancer Immunotherapy, USA., Greenbaum BD; Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Physiology, Biophysics, & Systems Biology, Weill Cornell Medicine, New York, NY 10065, USA., Komarova AV; Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France.; Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France.
Jazyk: angličtina
Zdroj: IScience [iScience] 2022 Jun 11; Vol. 25 (7), pp. 104599. Date of Electronic Publication: 2022 Jun 11 (Print Publication: 2022).
DOI: 10.1016/j.isci.2022.104599
Abstrakt: 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.
Competing Interests: The authors declare no conflicting interests.
(© 2022 The Authors.)
Databáze: MEDLINE