HIV-Bearing DCs Regulate T Cell Migration and Cell-Cell Contact Dynamics to Enhance Viral Spread

Abstract

The trafficking of cell-associated HIV from the genital mucosa to lymphoid organs represents a critical first step towards systemic infection. Mature DCs capture and transmit HIV to T cells, but insights into DC-to-T cell viral spread dynamics within a 3-dimensional environment is lacking. Using live-cell imaging, we show that mature DCs rapidly compartmentalize HIV within surface-accessible invaginations near the uropod. HIV capture did not interfere with DC migration towards lymph node homing chemo-attractants and their ability to enter lymphatic vessels. However, HIV-bearing DCs engaged in prolonged contacts with autologous CD4+ T cells which led to high T cell infection. Interestingly, we show that surface bound, virion-associated Env induced signal transduction in motile T cells that facilitated prolonged DC:T cell interactions, partially through high-affinity LFA-1 expression. Together, we describe a mechanism by which surface bound HIV particles function as signaling receptors that regulate T cell motility, cell-cell contact dynamics and productive infection.