Unbiased proteomic profiling of host cell extracellular vesicle composition and dynamics upon HIV-1 infection

Lorena Martin-Jaular, Nathalie Nevo, Julia P. Schessner, Mercedes Tkach, Mabel Jouve, Florent Dingli, Damarys Loew, Kenneth W. Witwer, Matias Ostrowski, Georg H.H. Borner, Clotilde Théry

Research output: Contribution to journalArticlepeer-review

Abstract

Cells release diverse types of extracellular vesicles (EVs), which transfer complex signals to surrounding cells. Specific markers to distinguish different EVs (e.g. exosomes, ectosomes, enveloped viruses like HIV) are still lacking. We have developed a proteomic profiling approach for characterizing EV subtype composition and applied it to human Jurkat T cells. We generated an interactive database to define groups of proteins with similar profiles, suggesting release in similar EVs. Biochemical validation confirmed the presence of preferred partners of commonly used exosome markers in EVs: CD81/ADAM10/ITGB1, and CD63/syntenin. We then compared EVs from control and HIV-1-infected cells. HIV infection altered EV profiles of several cellular proteins, including MOV10 and SPN, which became incorporated into HIV virions, and SERINC3, which was re-routed to non-viral EVs in a Nef-dependent manner. Furthermore, we found that SERINC3 controls the surface composition of EVs. Our workflow provides an unbiased approach for identifying candidate markers and potential regulators of EV subtypes. It can be widely applied to in vitro experimental systems for investigating physiological or pathological modifications of EV release.

Original languageEnglish (US)
Article numbere105492
JournalEMBO Journal
Volume40
Issue number8
DOIs
StatePublished - Apr 15 2021

Keywords

  • HIV
  • T cells
  • exosomes
  • extracellular vesicles
  • proteomics

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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