Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection

doi:10.1073/pnas.0507995103

Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection

Department of Microbiology, Boston University School of Medicine, Boston, MA 02118

Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved November 21, 2005 (received for review September 13, 2005)

Abstract

Immature dendritic cells (DCs) capture HIV type 1 (HIV-1) and can transmit captured virus particles to T cells. In this report, we show that HIV-1 particles captured by DCs can be transmitted to T cells by exocytosis without de novo infection. Captured HIV-1 particles were rapidly endocytosed to tetraspan protein (CD9, CD63)-positive endocytic compartments that were reminiscent of multivesicular endosomal bodies. Furthermore, some of the endocytosed virus particles were constitutively released into the extracellular milieu in association with HLA-DR1⁺, CD1b⁺, CD9⁺, and CD63⁺ vesicles (exosomes) and could initiate productive infections of CD4⁺ target cells. Surprisingly, the exocytosed vesicle-associated HIV-1 particles from DCs were 10-fold more infectious on a perparticle basis than cell-free virus particles. These studies describe a previously undescribed mechanism of DC-mediated HIV-1 transmission and suggest that virus particle trafficking to multivesicular endosomal bodies and subsequent exocytosis can provide HIV-1 particles captured by DCs an avenue for immune escape.

Footnotes

↵ * To whom correspondence should be addressed. E-mail: rgummulu{at}bu.edu.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: DC, dendritic cell; HIV-1, HIV type 1; env, virus envelope glycoprotein; MVB, multivesicular endosomal bodies; SFV, Semliki forest virus; moi, multiplicity of infection.