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| Status |
Public on Apr 29, 2022 |
| Title |
Viral Mimicry by Endogenous Y-RNAs Contributes to Antiviral Immunity [HIV] |
| Organisms |
Homo sapiens; Human immunodeficiency virus 1 |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pattern recognition receptors (PRRs) protect against host invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. While microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation during viral infection remain overlooked. In this work, we characterize the landscape of endogenous ligands that engage RIG-I-like receptors upon infection by a positive-sense RNA virus, a negative-sense RNA virus or a retrovirus. We found that several endogenous RNAs transcribed by RNA polymerase 3 (Pol3), and in particular the Y-RNA family of small non-coding repeats, bind and activate RIG-I. We show that this recognition is dependent on Y-RNA mimicking viral secondary structure and its 5’-triphosphate extremity. Further, we found that HIV-1 infection triggers a VPR-dependent downregulation of RNA triphosphatase DUSP11 in vitro and in vivo, leading to an increase of Y-RNA 5’-triphosphorylation that enables their immunogenicity. Importantly, we show that altering DUSP11 expression is sufficient to induce a type-I interferon and T cell activation transcriptional program associated with HIV-1 infection. Overall, our work uncovers the critical contribution of endogenous RNAs ligands to antiviral immunity and demonstrates the role of this pathway in HIV-1
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| Overall design |
For each experimental condition three biological replicates were performed each time. No data were excluded from analysis
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| Contributor(s) |
VABRET N, NAJBURG V, SOLOVYOV A, ŠULC P, BALAN S, BEAUCLAIR G, CHAZAL M, VARET H, LEGENDRE R, SISMEIRO O, DAVID RY, McCLAIN C, GOPAL R, CHAUVEAU L, SCHWARTZ O, JOUVENET N, MARKOWITZ M, TANGY F, BHARDWAJ N, GREENBAUM BD, KOMAROVA AV |
| Citation(s) |
35789859 |
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| Submission date |
Jul 25, 2019 |
| Last update date |
Jul 14, 2022 |
| Contact name |
Rachel Legendre |
| E-mail(s) |
rachel.legendre@pasteur.fr
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| Organization name |
Institut Pasteur
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| Department |
Research and Resource Center for Scientific Informatics
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| Lab |
Hub of Bioinformatics and Biostatistics
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| Street address |
28, rue du docteur Roux
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| City |
Paris |
| ZIP/Postal code |
75724 |
| Country |
France |
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| Platforms (1) |
| GPL26693 |
Illumina HiSeq 2500 (Homo sapiens; Human immunodeficiency virus 1) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE134861 |
Viral Mimicry by Endogenous Y-RNAs Contributes to Antiviral Immunity |
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| Relations |
| BioProject |
PRJNA556651 |
| SRA |
SRP216378 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE134857_RAW.tar |
660.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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