Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4+ T cells

Abstract

Cell-free human T-lymphotropic virus type 1 (HTLV-1) virions are poorly infectious in vitro for their primary target cells, CD4(+) T cells. Here, we show that HTLV-1 can efficiently infect myeloid and plasmacytoid dendritic cells (DCs). Moreover, DCs exposed to HTLV-1, both before and after being productively infected, can rapidly, efficiently and reproducibly transfer virus to autologous primary CD4(+) T cells. This DC-mediated transfer of HTLV-1 involves heparan sulfate proteoglycans and neuropilin-1 and results in long-term productive infection and interleukin-2-independent transformation of the CD4(+) T cells. These studies, along with observations of HTLV-1-infected DCs in the peripheral blood of infected individuals, indicate that DCs have a central role in HTLV-1 transmission, dissemination and persistence in vivo. In addition to altering the current paradigm concerning how HTLV-1 transmission occurs, these studies suggest that impairment of DC function after HTLV-1 infection plays a part in pathogenesis.

miR-28-3p Is a Cellular Restriction Factor That Inhibits Human T Cell Leukemia Virus, Type 1 (HTLV-1) Replication and Virus Infection

“…Despite a report of cell-free virion infection in dendritic cells (45), this system is difficult and relatively inefficient. HTLV-1 cell-free virus preparations are largely not infectious.…”

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

“…Transmission of HTLV-1 to T cells and to dendritic cells is more efficient by cell-to-cell contact (30,31). Upon contact of a target T cell with an HTLV-1-infected T cell, the MTOC reorients toward the cell-to-cell junction (26).…”

Mechanisms of HTLV-1 persistence and transformation

“…CD4 þ T-cells in a biphasic manner (Jones et al, 2008). During the first day after viral exposure, DCs capture and transfer virions to CD4 þ T…”