TY  - JOUR
AU  - Bertrand, Lisa
AU  - Nelde, Annika
AU  - Ramirez, Bertha Cecilia
AU  - Hatin, Isabelle
AU  - Arbes, Hugo
AU  - François, Pauline
AU  - Demais, Stéphane
AU  - Labaronne, Emmanuel
AU  - Decimo, Didier
AU  - Guiguettaz, Laura
AU  - Grégoire, Sylvie
AU  - Bet, Anne
AU  - Beauclair, Guillaume
AU  - Gross, Antoine
AU  - Ziegler, Maja C
AU  - Pereira, Mathias
AU  - Jeger-Madiot, Raphaël
AU  - Verdier, Yann
AU  - Vinh, Joelle
AU  - Cardinaud, Sylvain
AU  - Graff-Dubois, Stéphanie
AU  - Esclatine, Audrey
AU  - Gouttefangeas, Cécile
AU  - Altfeld, Marcus
AU  - Hocqueloux, Laurent
AU  - Samri, Assia
AU  - Autran, Brigitte
AU  - Lambotte, Olivier
AU  - Rammensee, Hans-Georg
AU  - Ricci, Emiliano P
AU  - Walz, Juliane
AU  - Namy, Olivier
AU  - Moris, Arnaud
TI  - Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00393
SP  - 1707
PY  - 2025
AB  - 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.
KW  - HIV-1: genetics
KW  - HIV-1: immunology
KW  - Humans
KW  - Open Reading Frames: genetics
KW  - CD4-Positive T-Lymphocytes: immunology
KW  - Ribosomes: metabolism
KW  - HIV Infections: immunology
KW  - HIV Infections: virology
KW  - HIV Infections: genetics
KW  - CD8-Positive T-Lymphocytes: immunology
KW  - Genome, Viral
KW  - Amino Acid Sequence
KW  - Conserved Sequence
KW  - Male
KW  - Peptides: immunology
KW  - Peptides: chemistry
KW  - Peptides: genetics
KW  - Ribosome Profiling
KW  - Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39966340
DO  - DOI:10.1038/s41467-025-56773-2
UR  - https://inrepo02.dkfz.de/record/298964
ER  -