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

By 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 Fernández-Figueras, Landon Moore, Bonaventura Clotet, Suryaram Gummuluru and Javier Martinez-Picado

Abstract

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

Topics: Immunobiology
Publisher: American Society of Hematology
OAI identifier: oai:pubmedcentral.nih.gov:2661860
Provided by: PubMed Central
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