Investigation of CD8+ T Cell Immunity in Zika Virus Infection Using Mouse Models

Abstract

Abstract CD8+ T cells may play a dual role in both protection against and pathogenesis of Flaviviruses, including Zika virus (ZIKV). However, virtually nothing is currently known about the role CD8+ T cells play during ZIKV infection in humans and animal models. The goal of our study is to investigate the role of CD8+ T cells during primary ZIKV infection in mice. Using LysMCre+IFNARfl/fl C57BL/6 (H-2b) mice that lack type I IFN receptor in a subset of myeloid cells, we characterized a new mouse model susceptible to infection with both East African lineage (MR766) and Asian lineage (FSS13025) ZIKV strains. A screening of 244 ZIKV epitopes predicted to bind H-2b class I molecules, defined a specific map of 26 and 15 peptides for MR766 and FSS13025 ZIKV strains, respectively. Intracellular cytokine staining confirmed the identity of these epitopes and demonstrated induction of polyfunctional ZIKV-specific CD8+ T cells. Furthermore, adoptive transfer of ZIKV-immune CD8+ T cells reduced viral burdens, whereas depletion of CD8+ T cells led to higher tissue burdens and mortality was increased in ZIKV-infected CD8−/− mice compared to Wild-type. These results demonstrate that CD8+ T cells are important mediators of protection during primary ZIKV infection and provide a H-2b mouse model for investigating ZIKV-specific CD8+ T cell responses. Based on these findings, studies are in progress towards defining the role of resident memory CD8+ T cells in protection against ZIKV infection using our recently developed mouse models of ZIKV systemic infection and sexual transmission.