Dendritic cell maturation,but not type I interferon exposure,restricts infection by HTLV-1,and viral transmission to T-cells

Human t lymphotropic virus type 1 (htlv-1) is the etiological agent of adult t cell leukemia/lymphoma (atll) and htlv-1-associated myelopathy/tropical spastic paraparesis (ham/tsp). both cd4+t-cells and dendritic cells (dcs) infected with htlv-1 are found in peripheral blood from htlv-1 carriers. we previously demonstrated that monocyte-derived il-4 dcs are more susceptible to htlv-1 infection than autologous primary t-cells,suggesting that dc infection precedes t-cell infection. however,during blood transmission,breast-feeding or sexual transmission,htlv-1 may encounter different dc subsets present in the blood,the intestinal or genital mucosa respectively. these different contacts may impact htlv-1 ability to infect dcs and its subsequent transfer to t-cells. using in vitro monocyte-derived il-4 dcs,tgf-β dcs and ifn-α dcs that mimic dcs contacting htlv-1 in vivo,we show here that despite their increased ability to capture htlv-1 virions,ifn-α dcs restrict htlv-1 productive infection. surprisingly,we then demonstrate that it is not due to the antiviral activity of type–i interferon produced by ifn-α dcs,but that it is likely to be linked to a distinct trafficking route of htlv-1 in il-4 dcs vs. ifn-α dcs. finally,we demonstrate that,in contrast to il-4 dcs,ifn-α dcs are impaired in their capacity to transfer htlv-1 to cd4 t-cells,both after viral capture and trans-infection and after their productive infection. in conclusion,the nature of the dcs encountered by htlv-1 upon primo-infection and the viral trafficking route through the vesicular pathway of these cells determine the efficiency of viral transmission to t-cells,which may condition the fate of infection. © 2017 rizkallah et al.