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

Abstract

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 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.

Keywords: CD8(+) T cell; LysMCre(+)IFNAR(fl/fl); Zika virus; epitope; mouse model; peptide.