In vitro, dendritic cells (DCs) capture and transmit intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. During trans-infection, HIV and its receptors are recruited to the site of DC T cell contact known as the infectious synapse and transfer of virions occurs via the synapse. In this study, we used fluorescent microscopy to find out the route of the trafficking of individual HIV particles in DCs during virus uptake and trans-infection. Mature DCs rapidly sequestered 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 reoriented to the infectious synapse after contact with a T cell. Mature DCs were observed to transfer HIV from the compartment to T cells. The compartmentalized HIV was fully accessible to surface-applied probes such as HIV envelope-specific inhibitors and other membrane-impermeable molecules, demonstrating that HIV accumulates in an invaginated domain within mature DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection.
We found that HCMV, MV, and HCV were trafficked to the CD81+ HIV-containing compartment, suggesting that virus concentration is a general phenomenon mediated by mature DCs. However, virus transmission was a target-cell dependent process. The comparison of the efficiency of virus transfer showed that CD4 T cells were efficiently trans-infected with HIV and fibroblasts were inefficiently with HCMV. Moreover, Vero cells were not even infected with MV just in the presence of mature DCs. We speculate that HIV uses the immunological interaction of mature DCs and T cells to enhance HIV infection of T cells.
Taken together, mature DC-mediated HIV trans-infection of T cells is a critical stage in the spread of HIV which can be exploited to not only gain a better understanding of cell to cell transmission of different types of viruses, but to possibly open new avenues for the control of HIV transmission.