Extensive uORF translation from HIV-1 transcripts conditions DDX3 dependency for expression of main ORFs and elicits specific T cell immune responses in infected individuals - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2022

Extensive uORF translation from HIV-1 transcripts conditions DDX3 dependency for expression of main ORFs and elicits specific T cell immune responses in infected individuals

Emmanuel Labaronne
Didier Décimo
Lisa Bertrand
Laura Guiguettaz
  • Fonction : Auteur
Thibault J.M. Sohier
David Cluet
Valérie Vivet-Boubou
Clara Dahoui
  • Fonction : Auteur
Pauline François
  • Fonction : Auteur
Isabelle Hatin
  • Fonction : Auteur
Olivier Lambotte
Assia Samri
Brigitte Autran
  • Fonction : Auteur
Lucie Etienne
Caroline Goujon
Jean-Christophe Paillart
Olivier Namy
Berta Cecilia Ramirez
  • Fonction : Auteur
Théophile Ohlmann
Arnaud Moris
  • Fonction : Auteur
  • PersonId : 1049969
Emiliano Ricci

Résumé

Abstract Human immunodeficiency virus type-1 (HIV-1) is a complex retrovirus which relies on alternative splicing, translational and post-translational mechanisms to produce more than 15 functional proteins from its single ∼10kb transcriptional unit. Here, we have applied ribosome profiling and nascent protein labeling at different time points during infection of CD4+ T lymphocytes to characterize the translational landscape of cellular and viral transcripts during the course of infection. Our results indicate a strong impact of viral infection on host cellular transcript levels but a modest impact on global translation rates. Analysis of ribosome profiling reads from viral transcripts reveals extensive and productive non-AUG translation of small peptides from multiple upstream open reading-frames (uORFs) located in the 5’ long terminal repeat. Remarkably, these uORFs derived peptides elicit specific T cell responses in HIV-infected individuals. uORFs are conserved among other retroviruses and, together with the TAR sequence, condition the dependency on DDX3 for efficient translation of the main viral open-reading frames.

Dates et versions

hal-03855362 , version 1 (16-11-2022)

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Emmanuel Labaronne, Didier Décimo, Lisa Bertrand, Laura Guiguettaz, Thibault J.M. Sohier, et al.. Extensive uORF translation from HIV-1 transcripts conditions DDX3 dependency for expression of main ORFs and elicits specific T cell immune responses in infected individuals. 2022. ⟨hal-03855362⟩
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