HIV traffics through a specialized, surface-accessible intracellular compartment during trans-infection of T cells by mature dendritic cells.

PLoS Pathogens
Hyun Jae YuDavid McDonald

Abstract

In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC-T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate tha...Continue Reading

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Citations

Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Richard L FeltsSriram Subramaniam
Nov 22, 2014·The Journal of Infectious Diseases·Suryaram GummuluruHisashi Akiyama
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