How Does Susceptibility to HTLV-1 Infection Varies With the Maturation State of Dendritic Cells?

Abstract

Keywords: dendritic cells • dendritic cell maturation • HTLV-1 infection • viral infectionHuman T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy. In patients, the provirus is detected in CD4 + T cells. HTLV-1 also infects blood or monocyte-derived dendritic cells (DCs) in vitro. Since DCs are more susceptible to HTLV-1 infection than autologous T cells, it has been suggested that they might be intermediaries for the viral spread to lymphocytes. DCs can switch from an immature to a mature state after contact with pathogens. In other viral infection, mature DCs are more efficient than immature DCs in viral transmission to T cells. In this editorial, we highlight a work demonstrating that mature DCs are unable to transmit HTLV-1 to T cells and discuss the mechanism of such restriction.HTLV-1 was identified as the first human oncogenic retrovirus [1,2]. It is the etiological agent of adult T-cell leukemia (ATL), an oligoclonal malignancy of infected CD4 + T lymphocytes, and of tropical spastic paraparesis, a chronic progressive inflammatory disease. Five to ten million individuals are HTLV-1 carriers worldwide [3], a probably underestimated number. HTLV-1 inter-individual transmission relies on mother-to-child transmission through prolonged breastfeeding, on sexual transmission and on transmission with contaminated blood products [4].In chronically infected individuals, HTLV-1 proviral DNA is mainly found in CD4 + T cells, but several reports have demonstrated that others immune cell types are infected by HTLV-1 in vivo [5][6][7]. These cell types include DCs, which are specialized antigen-presenting cells and essential mediators in shaping innate and adaptive immunity [8]. In vitro studies conducted by our lab and others confirmed that HTLV-1 productively infects myeloid blood DCs [7] and monocyte-derived DCs (MDDCs) [9][10][11]. Of note, exposure of target cells to cell-free viruses only leads to very low levels of productive infection [9], consistent with the observation that efficient infection of target cells requires close cell-to-cell contacts with infected donor cells [12]. Viral entry in T cells requires expression of the HTLV-1 receptor complex, in other words, neuropilin-1 and heparan sulfate proteoglycans, used for binding [13], and the glucose transporter Glut-1, required for fusion [14], while viral binding to DCs was also shown to require DC-SIGN [11].Importantly, we demonstrated that primary MDDCs are more susceptible to productive HTLV-1 infection than their autologous T cells [9]. Given that productively infected MDDCs are able to transfer HTLV-1 to T cells [7,9,11], it is thus proposed that DCs might be important intermediaries for HTLV-1 spread to T cells in newly infected individuals.Upon stimulation, DCs can switch from an immature to a mature state characterized by morphological, phenotypic and functional changes [15]. Interestingly, in the context of HIV-1, another retrovirus that spreads from DCs to T cells in ne...