Mapping and Role of the CD8+ T Cell Response During Primary Zika Virus Infection in Mice

CD8(+) 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(+)IFNAR(fl/fl) C57BL/6 (H-2(b)) mice lacking the type I interferon receptor in a subset ofmyeloid cells. In total, 26 and 15CD8(+) 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 highermortality 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.