HIV Hijacks Exosomes

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Science  27 Jan 2006:
Vol. 311, Issue 5760, pp. 437-439
DOI: 10.1126/science.311.5760.437d

Understanding the mechanisms by which HIV infects cells is a key step in developing effective treatments. Wiley and Gummuluru describe how immature dendritic cells of the immune system can capture HIV particles and, soon after internalization, transmit them to T cells without themselves becoming infected.

Dendritic cells are one of the first immune cell types encountered by incoming virus particles in the mucosa. HIV particles bind to dendritic cells and are internalized, ending up in multivesicular endosomes. Dendritic cells constitutively release some of the internal vesicles from multivesicular endosomes—so-called exosomes—into the extracellular milieu. For dendritic cells that have recently internalized HIV, it appears that the exosomes contain intact infectious HIV particles, which can then infect CD4+ target T cells. Indeed, the exosome-associated virus particles are up to 10-fold more infectious per particle than are cell-free virus preparations. The remaining dendritic cell-associated virus is transported from multivesicular endosomes to lysosomes and degraded. This exosomal pathway may explain how HIV can evade immune destruction even after having entered the wrong target cell of the immune system. The relative importance of this pathway—in comparison to the so-called infectious synapse, wherein dendritic cells directly pass HIV on to target T cells—remains to be established. — SMH

Proc. Natl. Acad. Sci. U.S.A. 103, 738 (2006).

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