Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling
Abstract The development of ribosomal profiling (Riboseq) revealed the immense coding capacity of human and viral genomes. Here, we used Riboseq to delineate the translatome of HIV-1 in infected CD4+ T cells. In addition to canonical viral protein coding sequences (CDSs), we identify 98 alternative...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56773-2 |
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| author | Lisa Bertrand Annika Nelde Bertha Cecilia Ramirez Isabelle Hatin Hugo Arbes Pauline François Stéphane Demais Emmanuel Labaronne Didier Decimo Laura Guiguettaz Sylvie Grégoire Anne Bet Guillaume Beauclair Antoine Gross Maja C. Ziegler Mathias Pereira Raphaël Jeger-Madiot Yann Verdier Joelle Vinh Sylvain Cardinaud Stéphanie Graff-Dubois Audrey Esclatine Cécile Gouttefangeas Marcus Altfeld Laurent Hocqueloux Assia Samri Brigitte Autran Olivier Lambotte Hans-Georg Rammensee Emiliano P. Ricci Juliane Walz Olivier Namy Arnaud Moris |
| author_facet | Lisa Bertrand Annika Nelde Bertha Cecilia Ramirez Isabelle Hatin Hugo Arbes Pauline François Stéphane Demais Emmanuel Labaronne Didier Decimo Laura Guiguettaz Sylvie Grégoire Anne Bet Guillaume Beauclair Antoine Gross Maja C. Ziegler Mathias Pereira Raphaël Jeger-Madiot Yann Verdier Joelle Vinh Sylvain Cardinaud Stéphanie Graff-Dubois Audrey Esclatine Cécile Gouttefangeas Marcus Altfeld Laurent Hocqueloux Assia Samri Brigitte Autran Olivier Lambotte Hans-Georg Rammensee Emiliano P. Ricci Juliane Walz Olivier Namy Arnaud Moris |
| author_sort | Lisa Bertrand |
| collection | DOAJ |
| description | Abstract The development of ribosomal profiling (Riboseq) revealed the immense coding capacity of human and viral genomes. Here, we used Riboseq to delineate the translatome of HIV-1 in infected CD4+ T cells. In addition to canonical viral protein coding sequences (CDSs), we identify 98 alternative open reading frames (ARFs), corresponding to small Open Reading Frames (sORFs) that are distributed across the HIV genome including the UTR regions. Using a database of HIV genomes, we observe that most ARF amino-acid sequences are likely conserved among clade B and C of HIV-1, with 8 ARF-encoded amino-acid sequences being more conserved than the overlapping CDSs. Using T cell-based assays and mass spectrometry-based immunopeptidomics, we demonstrate that ARFs encode viral polypeptides. In the blood of people living with HIV, ARF-derived peptides elicit potent poly-functional T cell responses mediated by both CD4+ and CD8+ T cells. Our discovery expands the list of conserved viral polypeptides that are targets for vaccination strategies and might reveal the existence of viral microproteins or pseudogenes. |
| format | Article |
| id | doaj-art-8cf55aa3c46745bca3f5db8083f8e746 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8cf55aa3c46745bca3f5db8083f8e7462025-08-20T02:59:58ZengNature PortfolioNature Communications2041-17232025-02-0116111810.1038/s41467-025-56773-2Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profilingLisa Bertrand0Annika Nelde1Bertha Cecilia Ramirez2Isabelle Hatin3Hugo Arbes4Pauline François5Stéphane Demais6Emmanuel Labaronne7Didier Decimo8Laura Guiguettaz9Sylvie Grégoire10Anne Bet11Guillaume Beauclair12Antoine Gross13Maja C. Ziegler14Mathias Pereira15Raphaël Jeger-Madiot16Yann Verdier17Joelle Vinh18Sylvain Cardinaud19Stéphanie Graff-Dubois20Audrey Esclatine21Cécile Gouttefangeas22Marcus Altfeld23Laurent Hocqueloux24Assia Samri25Brigitte Autran26Olivier Lambotte27Hans-Georg Rammensee28Emiliano P. Ricci29Juliane Walz30Olivier Namy31Arnaud Moris32Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Department of Peptide-based Immunotherapy, University and University Hospital TübingenUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Laboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR 5239, Inserm, U1293, Université Claude Bernard Lyon 1, 46 allée d’Italie F-69364CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de LyonLaboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR 5239, Inserm, U1293, Université Claude Bernard Lyon 1, 46 allée d’Italie F-69364Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Sorbonne Université, Inserm U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)IRIM, UMR 9004, CNRS, Université de MontpellierLeibniz Institute of VirologyUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Sorbonne Université, Inserm U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)ESPCI Paris, PSL University, Spectrométrie de Masse Biologique et ProtéomiqueESPCI Paris, PSL University, Spectrométrie de Masse Biologique et ProtéomiqueSorbonne Université, Inserm U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)Sorbonne Université, Inserm U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Institute of Immunology, University of TübingenLeibniz Institute of VirologyCentre Hospitalier Universitaire d’OrléansSorbonne Université, Inserm U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)Sorbonne Université, Inserm U1135, CNRS ERL 8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)Université Paris Saclay, Inserm, CEA, AP-HP, UMR1184 IDMIT, Department of Internal Medicine & Clinical Immunology, Bicêtre Hospital, Le Kremlin-BicêtreInstitute of Immunology, University of TübingenLaboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR 5239, Inserm, U1293, Université Claude Bernard Lyon 1, 46 allée d’Italie F-69364Department of Peptide-based Immunotherapy, University and University Hospital TübingenUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Abstract The development of ribosomal profiling (Riboseq) revealed the immense coding capacity of human and viral genomes. Here, we used Riboseq to delineate the translatome of HIV-1 in infected CD4+ T cells. In addition to canonical viral protein coding sequences (CDSs), we identify 98 alternative open reading frames (ARFs), corresponding to small Open Reading Frames (sORFs) that are distributed across the HIV genome including the UTR regions. Using a database of HIV genomes, we observe that most ARF amino-acid sequences are likely conserved among clade B and C of HIV-1, with 8 ARF-encoded amino-acid sequences being more conserved than the overlapping CDSs. Using T cell-based assays and mass spectrometry-based immunopeptidomics, we demonstrate that ARFs encode viral polypeptides. In the blood of people living with HIV, ARF-derived peptides elicit potent poly-functional T cell responses mediated by both CD4+ and CD8+ T cells. Our discovery expands the list of conserved viral polypeptides that are targets for vaccination strategies and might reveal the existence of viral microproteins or pseudogenes.https://doi.org/10.1038/s41467-025-56773-2 |
| spellingShingle | Lisa Bertrand Annika Nelde Bertha Cecilia Ramirez Isabelle Hatin Hugo Arbes Pauline François Stéphane Demais Emmanuel Labaronne Didier Decimo Laura Guiguettaz Sylvie Grégoire Anne Bet Guillaume Beauclair Antoine Gross Maja C. Ziegler Mathias Pereira Raphaël Jeger-Madiot Yann Verdier Joelle Vinh Sylvain Cardinaud Stéphanie Graff-Dubois Audrey Esclatine Cécile Gouttefangeas Marcus Altfeld Laurent Hocqueloux Assia Samri Brigitte Autran Olivier Lambotte Hans-Georg Rammensee Emiliano P. Ricci Juliane Walz Olivier Namy Arnaud Moris Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling Nature Communications |
| title | Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling |
| title_full | Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling |
| title_fullStr | Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling |
| title_full_unstemmed | Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling |
| title_short | Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling |
| title_sort | unveiling conserved hiv 1 open reading frames encoding t cell antigens using ribosome profiling |
| url | https://doi.org/10.1038/s41467-025-56773-2 |
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