Abstract

Highlights•LysMCre+IFNARfl/fl mice developed as a model to investigate T cell responses to ZIKV•ZIKV infection elicits CD8+ T cells targeting viral PrM, E, and NS5 proteins in mice•ZIKV-immune CD8+ T cell transfer reduced while depletion increased viral burdens in mice•CD8−/− mice displayed higher mortality with ZIKV infectionSummaryCD8+ T cells may play a dual role in protection against and pathogenesis of flaviviruses, including Zika virus (ZIKV). We evaluated the CD8+ T cell response in ZIKV-infected LysMCre+IFNARfl/fl C57BL/6 (H-2b) mice lacking the type I interferon receptor in a subset of myeloid cells. In total, 26 and 15 CD8+ T cell-reactive peptides for ZIKV African (MR766) and Asian (FSS13025) lineage strains, respectively, were identified and validated. CD8+ T cells from infected mice were polyfunctional and mediated cytotoxicity. Adoptive transfer of ZIKV-immune CD8+ T cells reduced viral burdens, whereas their depletion led to higher tissue burdens, and CD8−/− mice displayed higher mortality with ZIKV infection. Collectively, these results demonstrate that CD8+ T cells protect against ZIKV infection. Further, this study provides a T cell competent mouse model for investigating ZIKV-specific T cell responses.Graphical abstract