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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月18日

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  • 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,
  • Emiliano P. Ricci

摘要

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.