HIV-Captured DCs Regulate T Cell Migration and Cell-Cell Contact Dynamics to Enhance Viral Spread
Wan Hon Koh,
Paul Lopez,
Oluwaseun Ajibola,
Roshan Parvarchian,
Umar Mohammad,
Ryan Hnatiuk,
Jason Kindrachuk,
Thomas T. Murooka
Affiliations
Wan Hon Koh
University of Manitoba, Rady Faculty of Health Sciences, Department of Immunology, Winnipeg, MB, Canada
Paul Lopez
University of Manitoba, Rady Faculty of Health Sciences, Department of Immunology, Winnipeg, MB, Canada
Oluwaseun Ajibola
University of Manitoba, Rady Faculty of Health Sciences, Department of Immunology, Winnipeg, MB, Canada
Roshan Parvarchian
University of Manitoba, Rady Faculty of Health Sciences, Department of Immunology, Winnipeg, MB, Canada
Umar Mohammad
University of Manitoba, Rady Faculty of Health Sciences, Department of Immunology, Winnipeg, MB, Canada
Ryan Hnatiuk
University of Manitoba, Rady Faculty of Health Sciences, Department of Immunology, Winnipeg, MB, Canada
Jason Kindrachuk
University of Manitoba, Rady Faculty of Health Sciences, Department of Medical Microbiology and Infectious Diseases, Winnipeg, Canada
Thomas T. Murooka
University of Manitoba, Rady Faculty of Health Sciences, Department of Immunology, Winnipeg, MB, Canada; University of Manitoba, Rady Faculty of Health Sciences, Department of Medical Microbiology and Infectious Diseases, Winnipeg, Canada; Corresponding author
Summary: Trafficking of cell-associated HIV-1 from the genital mucosa to lymphoid organs represents a critical first step toward systemic infection. Mature DCs capture and transmit HIV-1 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-1 within surface-accessible invaginations near the uropod. HIV-1 capture did not interfere with DC migration toward lymph node homing chemo-attractants and their ability to enter lymphatic vessels. However, HIV-captured 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-1 particles function as signaling receptors that regulate T cell motility, cell-cell contact dynamics, and productive infection.
