Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity

An expansion of effector/activated V delta 2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of V delta 2 T-cells against ZIKV-infected cells. The V delta 2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce V delta 2 T-cells expansion and sensitized A549 cells to V delta 2-mediated killing. Indeed, expanded V delta 2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing V delta 2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded V delta 2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated V delta 2 cytotoxicity. Our data showed a strong antiviral activity of V delta 2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of V delta 2 T-cells expansion in vivo may be associated with disease complications.