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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2732-2741.
Prepublished online as a Blood First Edition Paper on October 22, 2008; DOI 10.1182/blood-2008-05-158642.
 Previous Article | Next Article 
Submitted May 22, 2008
Accepted September 28, 2008
Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway
Nuria Izquierdo-Useros, Mar Naranjo-Gomez, Jacob Archer, Steven C. Hatch, Itziar Erkizia, Julia Blanco, Francesc E. Borras, Maria Carmen Puertas, John H Connor, Maria Teresa Fernandez-Figueras, Landon Moore, Bonaventura Clotet, Suryaram Gummuluru, and Javier Martinez-Picado*
IrsiCaixa Foundation, Badalona, Spain
Laboratory of Immunobiology for Research and Application to Diagnosis (LIRAD), Blood and Tissue Bank, Universitat Autonoma de Barcelona, Badalona, Spain
Department of Microbiology, Boston University School of Medicine, Boston, MA, United States
Department of Pathology, Institut d'Investigacio en Ciences de la Salut Germans Trias i Pujol, Badalona, Spain
Department of Genetics and Genomics, Boston University School of Medicine, Boston, MA, United States
Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain
* Corresponding author; email: jmpicado{at}irsicaixa.es.
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 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-eGFP viral like particles (VLPs) and exosomes by DCs was upregulated 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.
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