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

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, nascent protein labelling and quantitative mass-spectrometry 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. Interestingly, 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 prime long terminal repeat. Remarkably, uORF-derived peptides elicit specific T cell responses in people living with HIV suggesting a potential role in the progression of the disease. uORF translation is 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Hiv-1 Vector Pnl4-3 (ncbitaxon:151458) Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Emiliano P. Ricci

PROVIDER: MSV000095969 | MassIVE |

REPOSITORIES: MassIVE

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