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

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.