Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling

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<sup>+</sup> 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<sup>+</sup> and CD8<sup>+</sup> 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.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-02-18
DOI
https://doi.org/10.1038/s41467-025-56773-2
Citations
7
Primary Topic
vaccines and immunoinformatics approaches
Type
article
Field-Weighted Citation Impact
5.64

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling

Cécile Gouttefangeas, Raphaël Jeger‐Madiot, Stéphanie Graff‐Dubois, Lisa Bertrand et al.
7 citations
Nature Communications
vaccines and immunoinformatics approaches
5.64
article

Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling

Cécile Gouttefangeas, Raphaël Jeger‐Madiot, Stéphanie Graff‐Dubois, Lisa Bertrand, Audrey Esclatine, Hugo Arbès, Joëlle Vinh, Olivier Namy, Yann Verdier, Mathias Pereira, Emiliano P. Ricci, Isabelle Hatin, Annika Nelde, Assia Samri, Sylvain Cardinaud, Brigitte Autran, Marcus Altfeld, Laura Guiguettaz, Anne Bet, Guillaume Beauclair, Antoine Gross, Didier Décimo, Laurent Hocqueloux, Stéphane Demais, Bertha Cecilia Ramírez, Olivier Lambotte, Arnaud Moris, Maja C. Ziegler, Emmanuel Labaronne, Juliane S. Walz, Hans‐Georg Rammensee, Pauline François, Sylvie Grégoire
article en
7 citations

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<sup>+</sup> 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<sup>+</sup> and CD8<sup>+</sup> 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.

Nature CommunicationsVol. 16(1)
Université Claude Bernard Lyon 1 (FR), École Normale Supérieure de Lyon (FR), Centre National de la Recherche Scientifique (FR), Leibniz Institute of Virology (LIV) (DE), Inserm (FR), German Cancer Research Center (DE), Université Paris-Est Créteil (FR), Université de Montpellier (FR), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), Université Paris Sciences et Lettres (FR), Université Paris-Saclay (FR), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut de Biologie Intégrative de la Cellule (FR), Institut de Recherche Vaccinale (FR), CEA Paris-Saclay (FR), Centre d'Immunologie et des Maladies Infectieuses (FR), Institut de Recherche en Infectiologie de Montpellier (FR), Centre hospitalier universitaire d'Orléans (FR), Institut Mondor de Recherche Biomédicale (FR), Centre International de Recherche en Infectiologie (FR), Bicêtre Hospital (FR), University of Tübingen (DE), ESPCI Paris (FR)
Styrelsen för Internationellt Utvecklingssamarbete, Sidaction, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Eberhard Karls Universität Tübingen, Deutsche Krebshilfe, Deutschen Konsortium für Translationale Krebsforschung, National Institutes of Health
Quality Education
Openalex Percentile: Top 4%
vaccines and immunoinformatics approaches
5.64
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.