Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway

Nuria Izquierdo-Useros, Mar Naranjo-Gómez, Jacob Archer, Steven C. Hatch, Itziar Erkizia, Julià Blanco, Francesc E. Borràs, Maria Carmen Puertas, John H. Connor, Maria Teresa Fernádez-Figueras, Landon Moore, Bonaventura Clotet, Suryaram Gummuluru, Javier Martinez-Picado

Research output: Contribution to journalArticleResearchpeer-review

164 Citations (Scopus)


Exosomes are secreted cellular vesicles that can be internalized by dendritic cells (DCs), contributing to antigen-specific naive CD4 + T-cell activation. Here, we demonstrate that human immunodeficiency virus type 1 (HIV-1) can exploit this exosome antigen-dissemination pathway intrinsic to mature DCs (mDCs) for mediating trans-infection of T lymphocytes. Capture of HIV-1, HIV-1 Gag-enhanced green fluorescent protein (eGFP) viral-like particles (VLPs), and exosomes by DCs was up-regulated upon maturation, resulting in localization within a CD81 + compartment. Uptake of VLPs or exosomes could be inhibited by a challenge with either particle, suggesting that the expression of common determinant(s) on VLP or exosome surface is necessary for internalization by mDCs. Capture by mDCs was insensitive to proteolysis but blocked when virus, VLPs, or exosomes were produced from cells treated with sphingolipid biosynthesis inhibitors that modulate the lipid composition of the budding particles. Finally, VLPs and exosomes captured by mDCs were transmitted to T lymphocytes in an envelope glycoprotein-independent manner, underscoring a new potential viral dissemination pathway. © 2009 by The American Society of Hematology.
Original languageEnglish
Pages (from-to)2732-2741
Issue number12
Publication statusPublished - 19 Mar 2009


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