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

RD Wiley, S Gummuluru - Proceedings of the National …, 2006 - National Acad Sciences
RD Wiley, S Gummuluru
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
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 …
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.
National Acad Sciences