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

Abstract

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.

Microbial Biofilms: Human T-cell Leukemia Virus Type 1 First in Line for Viral Biofilm but Far Behind Bacterial Biofilms

“…What are the molecular mechanisms that regulate these pathways? Moreover, is viral biofilm present on different HTLV-1 infected cell lines similar in terms of composition, structure, and topography, given that these infected cells have different infectivity and ability to escape to innate sensing (Alais et al, 2015;Assil et al, 2019)? Viral biofilm has only been reported in in vitro models using HTLV-1-infected cell lines (Pais-Correia et al, 2010;Nakamura et al, 2019).…”

“…For example, HTLV-1 entry in dendritic cells (DC) seems to rely on endocytosis, as inhibition of micropinocytosis or clathrindependent endocytosis completely abolished HTLV-1 capture by immature and mature DC, as well as subsequent productive infection of immature DC (Rizkallah et al, 2017). Besides, the role of Glut-1 in HTLV-1 viral biofilm entry in plasmacytoid dendritic cell (pDC) was confirmed, but not that of NRP-1 (Assil et al, 2019). In addition, while the same study also confirmed the role of Glut-1 in productive infection of T-cells after contact with HTLV-1 viral biofilm, it failed to demonstrate the need of NRP-1, suggesting that the proposed interaction of HTLV-1 envelop with NRP-1 as prerequisite before interaction with Glut-1 (Lambert et al, 2009) might not be mandatory when virions are embedded in biofilm and not cell-free.…”

“…Similar to bacterial biofilms, viral biofilms could also provide a physical barrier to prevent recognition by antibodies or immune cells. Assil et al showed that the HTLV-1 biofilm regulates IFN-I production by pDCs (Assil et al, 2019). The presence of the TF antigen, a desialylated Galβ1-3GalNAc glycosylated structure at the surface of the infected cells, in which viruses are embedded in biofilm, reduces the IFN-I response of pDCs (Assil et al, 2019).…”

“…Assil et al showed that the HTLV-1 biofilm regulates IFN-I production by pDCs (Assil et al, 2019). The presence of the TF antigen, a desialylated Galβ1-3GalNAc glycosylated structure at the surface of the infected cells, in which viruses are embedded in biofilm, reduces the IFN-I response of pDCs (Assil et al, 2019). Interestingly, the density of TF antigen at the surface of HTLV-1 infected cells positively regulates the ability of infected cells to transmit the virus and infect new target cells.…”

p30 protein: a critical regulator of HTLV-1 viral latency and host immunity

“…Lymphocytes are not the only cell type that HTLV-1 is able to infect. It has been reported that HTLV-1 can also infect monocytes/macrophages and dendritic cells [68][69][70][71][72][73][74][75][76], but their role in viral pathogenesis is not fully understood. In infected individuals, the majority of viral DNA is found in CD4 + and CD8 + T-cells.…”