Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation

Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells.Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production.Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection.We show that pDCs sense surface associated-HTLV present with glycan-rich structure referred to as biofilm-like structure, which thus represents a newly described viral structure triggering the antiviral response by pDCs.Consistently, heparan sulfate proteoglycans and especially the cell surface pattern of terminal β-galactoside glycosylation, modulate the transmission of the immunostimulatory RNA to pDCs.Altogether, our results uncover a function of virus-containing cell surface-associated glycosylated structures in the activation of innate immunity. Author summaryHuman T Lymphotropic virus type (HTLV) establishes persistent infections, leading to adult T-cell Leukemia, a life-threatening cancer in chronically-infected individuals.Viral persistence likely results from a failure of immune responses to eradicate viral replication, a least in part, by viral escape from innate immunity, and notably via decreased production of type I interferons (IFN-I) by infected cells.Plasmacytoid dendritic cells (pDCs) are known as robust producers of IFN-I in response to virus stimulation, thus bypassing the viral mechanisms to evade pathogen-sensing pathways in infected cells.However, HTLV particles are not detected in biological fluids of infected individuals, raising the question of the pDC-activating signal.Here, we demonstrate that pDCs produce IFN-I upon physical contacts with HTLV-infected cells.We show that pDCs sense surface associated-HTLV present with glycan-rich structure, referred to as HTLV-biofilm-like structure.Importantly, the sensing of infected cells by pDCs is modulated by the glycosylation