Article Dans Une Revue Nature Communications Année : 2025

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

Résumé

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.

Fichier principal
Vignette du fichier
41467_2025_Article_56773.pdf (3.15 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence

Dates et versions

hal-04958976 , version 1 (02-10-2025)

Licence

Identifiants

Citer

Lisa Bertrand, Annika Nelde, Bertha Cecilia Ramirez, Isabelle Hatin, Hugo Arbes, et al.. Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling. Nature Communications, 2025, 16 (1), pp.1707. ⟨10.1038/s41467-025-56773-2⟩. ⟨hal-04958976⟩
361 Consultations
110 Téléchargements

Altmetric

Partager

  • More