@article{7fcaed5213bf4435b39ae8e9e7e3511d,
title = "Unbiased proteomic profiling of host cell extracellular vesicle composition and dynamics upon HIV-1 infection",
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.",
keywords = "HIV, T cells, exosomes, extracellular vesicles, proteomics",
author = "Lorena Martin-Jaular and Nathalie Nevo and Schessner, {Julia P.} and Mercedes Tkach and Mabel Jouve and Florent Dingli and Damarys Loew and Witwer, {Kenneth W.} and Matias Ostrowski and Borner, {Georg H.H.} and Clotilde Th{\'e}ry",
note = "Funding Information: Clotilde Th?ry and her team acknowledge the following INSERM U932 members for providing tools and helpful discussions: Dr Nicolas Manel, Dr Philippe Benaroch, Dr Claire Hivroz, Dr Sebastian Amigorena, Dr Nicolas Ruffin, Dr Andr?s Zucchetti, St?phanie Dogniaux. The authors acknowledge the Cytometry platform at Institut Curie's Research Centre, and the assistance of its team to perform Cytometry. The work was funded by INSERM and Institut Curie and grants from NIDA (DA040385, to KWW, CT and MO, and DA047807, to KWW); ANRS (2015-1 CT, LMJ); SIDACTION (17-1-AAE-1138, CT); INCa (INCA-11548, CT), Fondation ARC (PGA1 RF20180206962, CT); French National Research Agency (ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043 and ANR-18-CE13-0017-03 to CT); and by the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director (UG3CA241694, to KWW). The Proteomic platform of Institut Curie is supported by ?R?gion Ile-de-France? and Fondation pour la Recherche M?dicale grants (to D.L.). Electron microscopy imaging was enabled by the French National Research Agency through the {"}Investments for the Future{"} program (France-BioImaging, ANR-10-INSB-04), and PICT-IBiSA, member of the France-BioImaging national research infrastructure, supported by the CelTisPhyBio Labex (N? ANR-10-LBX-0038) part of the IDEX PSL (No. ANR-10-IDEX-0001-02 PSL). Georg H. H. Borner and Julia Schessner were funded by the Max Planck Society for the Advancement of Science, and by the German Research Foundation (DFG/Gottfried Wilhelm Leibniz Prize MA 1764/2-1); they wish to thank Matthias Mann for his support. Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license",
year = "2021",
month = apr,
day = "15",
doi = "10.15252/embj.2020105492",
language = "English (US)",
volume = "40",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "8",
}