Non-AUG HIV-1 uORF translation elicits specific T cell immune response and regulates viral transcript expression

Emmanuel Labaronne, Didier Décimo, Lisa Bertrand, Laura Guiguettaz, Thibault J. M. Sohier, David Cluet, Valérie Vivet-Boudou, Ana Luiza Chaves Valadão, Clara Dahoui, Pauline François, Isabelle Hatin, Olivier Lambotte, Assia Samri, Brigitte Autran, Lucie Etienne, Caroline Goujon, Jean-Christophe Paillart, Olivier Namy, Bertha Cecilia Ramirez, Théophile Ohlmann, Arnaud Moris and Emiliano P. Ricci ()
Additional contact information
Emmanuel Labaronne: 46 allee d’Italie F-69364
Didier Décimo: F-69007
Lisa Bertrand: Institute for Integrative Biology of the Cell (I2BC)
Laura Guiguettaz: 46 allee d’Italie F-69364
Thibault J. M. Sohier: 46 allee d’Italie F-69364
David Cluet: 46 allee d’Italie F-69364
Valérie Vivet-Boudou: UPR9002
Ana Luiza Chaves Valadão: Montpellier University
Clara Dahoui: F-69007
Pauline François: Institute for Integrative Biology of the Cell (I2BC)
Isabelle Hatin: Institute for Integrative Biology of the Cell (I2BC)
Olivier Lambotte: Le Kremlin Bicêtre
Assia Samri: Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Brigitte Autran: Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)
Lucie Etienne: F-69007
Caroline Goujon: Montpellier University
Jean-Christophe Paillart: UPR9002
Olivier Namy: Institute for Integrative Biology of the Cell (I2BC)
Bertha Cecilia Ramirez: Institute for Integrative Biology of the Cell (I2BC)
Théophile Ohlmann: F-69007
Arnaud Moris: Institute for Integrative Biology of the Cell (I2BC)
Emiliano P. Ricci: 46 allee d’Italie F-69364

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract Human immunodeficiency virus type-1 (HIV-1) is a complex retrovirus that relies on alternative splicing, translational, and post-translational mechanisms to produce over 15 functional proteins from its single ~10 kb transcriptional unit. Using ribosome profiling, nascent protein labeling, RNA sequencing, and whole-proteomics of infected CD4 + T lymphocytes, we characterized the transcriptional, translational, and post-translational landscape during infection. While viral infection exerts a significant impact on host transcript abundance, global translation rates are only modestly affected. Proteomics data reveal extensive transcriptional and post-translational regulation, with many genes showing opposing trends between transcript/ribosome profiling and protein abundance. These findings highlight a complex regulatory network orchestrating gene expression at multiple levels. Viral ribosome profiling further uncovered extensive non-AUG translation of small peptides from upstream open reading frames (uORFs) within the 5’ long terminal repeat, which elicit specific T cell responses in people living with HIV. Conservation of uORF translation among retroviruses, along with TAR sequences, shapes DDX3 dependency for efficient translation of the main viral open reading frames.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56772-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56772-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56772-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().