iScience (Jul 2022)
Y RNAs are conserved endogenous RIG-I ligands across RNA virus infection and are targeted by HIV-1
- Nicolas Vabret,
- Valérie Najburg,
- Alexander Solovyov,
- Ramya Gopal,
- Christopher McClain,
- Petr Šulc,
- Sreekumar Balan,
- Yannis Rahou,
- Guillaume Beauclair,
- Maxime Chazal,
- Hugo Varet,
- Rachel Legendre,
- Odile Sismeiro,
- Raul Y. Sanchez David,
- Lise Chauveau,
- Nolwenn Jouvenet,
- Martin Markowitz,
- Sylvie van der Werf,
- Olivier Schwartz,
- Frédéric Tangy,
- Nina Bhardwaj,
- Benjamin D. Greenbaum,
- Anastassia V. Komarova
Affiliations
- Nicolas Vabret
- 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; Corresponding author
- Valérie Najburg
- Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Alexander Solovyov
- Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Ramya Gopal
- 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
- Christopher McClain
- 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
- Petr Šulc
- Center for Molecular Design and Biomimetics at the Biodesign Institute and School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA
- Sreekumar Balan
- 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
- Yannis Rahou
- Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Guillaume Beauclair
- Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Maxime Chazal
- Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Hugo Varet
- 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
- Rachel Legendre
- 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
- Odile Sismeiro
- 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
- Raul Y. Sanchez David
- Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Lise Chauveau
- Virus & Immunity Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Nolwenn Jouvenet
- Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Martin Markowitz
- Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY, USA
- Sylvie van der Werf
- Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Olivier Schwartz
- Virus & Immunity Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Frédéric Tangy
- Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, Université de Paris, CNRS UMR-3569, 75015 Paris, France
- Nina Bhardwaj
- 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
- Benjamin D. Greenbaum
- 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
- Anastassia V. Komarova
- 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; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 7
p. 104599
Abstract
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.
