In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions

Abstract

In the prevailing model of HIV-1 trans-infection, dendritic cells (DCs) capture and internalize intact virions and transfer these virions to interacting T cells at the virological synapse. Here, we show that HIV-1 virions transmitted in trans from in vitro derived DCs to T cells principally originate from the surface of DCs. Selective neutralization of surface-bound virions abrogated trans-infection by monocyte-derived DCs and CD34-derived Langerhans cells. Under conditions mimicking antigen recognition by the interacting T cells, most transferred virions still derived from the cell surface, although a few were transferred from an internal compartment. Our findings suggest that attachment inhibitors could neutralize trans-infection of T cells by DCs in vivo.

Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1

“…A recent report concluded that primarily cell-surfacebound HIV-1 is transferred to T cells (40), whereas previous studies have shown that mainly the internalized virus is transferred (37). These latter reports demonstrated that, although a large part of the virus is degraded in lysosomes (27,28), part of the virus recycles to infectious synapse (41,42) or exosomes (43).…”

Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

“…HIV-1 transmission in cis is characterized by direct infection of the DC, which takes a few days, resulting in transfer of de novo-produced virions (9,10). DC-mediated HIV-1 transmission in trans relies on the capture of HIV-1 particles, followed by transfer to HIV-1-susceptible CD4 cells.…”

“…DC-mediated HIV-1 transmission in trans relies on the capture of HIV-1 particles, followed by transfer to HIV-1-susceptible CD4 cells. Typically, trans-infection starts within a few hours following capture and can continue for a few days (9,11). Transmission of HIV-1 from DCs to CD4 + T lymphocytes occurs via formation of a virological synapse upon cell-cell contact (12)(13)(14)(15).…”

“…Transmission of HIV-1 from DCs to CD4 + T lymphocytes occurs via formation of a virological synapse upon cell-cell contact (12)(13)(14)(15). Cavrois et al (9) showed that membrane-bound HIV-1 was transmitted to susceptible cells, whereas internalized HIV-1 was degraded. Other studies reported that LPS-matured DCs recruited captured HIV-1 into deep, invaginated membrane pockets, where the virus is redirected to the virological synapse to be transmitted to HIV-1 susceptible cells (11,(16)(17)(18)(19).…”

HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate with Better T Cell Activation

“…It was proposed that HIV-1 takes advantage of a pre-existing exosome Ag-dissemination pathway intrinsic to mDC to enable final trans-infection of CD4 + T cells (10)(11)(12), whereas others investigators adduce that only DC surface-bound HIV-1 are able to trans-infect target cells (13). However, both models have been reconciled, demonstrating that LPS-matured DC (mDC LPS) concentrate HIV-1 in a tetra-spanin-rich compartment that remains physically connected to the extracellular milieu (9).…”