Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection.
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.
Wiley
Rebecca D
RD
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Gummuluru
Suryaram
S
D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D003713:Dendritic Cells / Q000502:physiology* / Q000648:ultrastructure / Q000821:virology*; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000502:physiology / Q000648:ultrastructure / Q000821:virology