Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling

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Бібліографічні деталі
Опубліковано в::Nature Communications vol. 16, no. 1 (2025), p. 1707
Опубліковано:
Nature Publishing Group
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024 7 |a 10.1038/s41467-025-56773-2  |2 doi 
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245 1 |a Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling 
260 |b Nature Publishing Group  |c 2025 
513 |a Journal Article 
520 3 |a 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.Here, using ribosomal profiling, the authors characterize the translatome of HIV-1 revealing tens of alternative open reading frames (ARF) that encode conserved viral antigens and show that ARF-derived peptides elicit potent HIV-specific poly-functional immune responses mediated by both CD4+ and CD8+ T cells. 
653 |a Mass spectrometry 
653 |a Open reading frames 
653 |a Genomes 
653 |a Lymphocytes T 
653 |a Pseudogenes 
653 |a Antigens 
653 |a CD4 antigen 
653 |a Human immunodeficiency virus--HIV 
653 |a Lymphocytes 
653 |a Amino acids 
653 |a Frames (data processing) 
653 |a Gene sequencing 
653 |a Mass spectroscopy 
653 |a Peptides 
653 |a Polypeptides 
653 |a Vaccination 
653 |a CD8 antigen 
773 0 |t Nature Communications  |g vol. 16, no. 1 (2025), p. 1707 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3168151781/abstract/embedded/H09TXR3UUZB2ISDL?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3168151781/fulltextPDF/embedded/H09TXR3UUZB2ISDL?source=fedsrch