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

[This corrects the article DOI: 10.1371/journal.ppat.1006353.].

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-ß 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.

[Intercellular transmission of HTLV-1: not all mechanisms have been revealed]. / Transmission intercellulaire de HTLV-1--Des mécanismes loin d'être complètement élucidés.

HTLV-1 is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and of HTLV-1-Associated Myelopathy/tropical spastic paraparesis (HAM/TSP). It is mainly detected in CD4+ lymphocytes in vivo, but proviral genomes have also been detected although less frequently, in CD8+ T lymphocytes, B lymphocytes, monocytes, macrophages, dendritic cells and other non-lymphoid cells. Virus spread is highly dependent on cell-cell contact. This mode of transmission is correlated with an increased ability of infected cells to migrate, a property linked to cytoskeleton reorganization induced by the viral Tax protein. Cell-to-cell transmission relies on at least three non-exclusive molecular pathways. First, a specialized area, the "virological synapse'' (VS) promotes direct transmission of budding HTLV-1 particles into a synaptic cleft formed between infected and uninfected cells. Second, HTLV-1 particles accumulate at the plasma membrane of infected cells in a biofilm-like extracellular viral assembly that resembles a bacterial biofilm. Viral biofilm is rapidly transmitted to uninfected cells when infected cells contact target cells. Finally, membrane extensions called inter-cellular conduits facilitate HTLV-1 proteins transfer from infected to uninfected target cells, and may stabilize cell-cell contacts. The aim of this review is to summarize the molecular mechanisms of these HTLV-1 transmission pathways.