Mapping and role of the CD8⁺ T cell response during primary Zika virus infection in mice

Elong Ngono, et al., Cell Host & Microbe. 2017. 21, 35–46.

Speaker: Wan-Yu Wang (王琬瑜)                                         Time: 13:10~14:00, Apr. 05, 2017

Commentator: Dr. Guey-Chuen Perng (彭貴春 老師)        Place: Room 601

Abstract:

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus. Although ZIKV infection is generally asymptomatic, it has been associated with neurological symptoms in adults and microcephaly in infants. To reduce ZIKV infection, host immunity against the virus needs to be evaluated. Previous study showed that CD8⁺ T cells play a protective role in dengue virus infection ^[1]. To investigate the role of CD8⁺ T cells in ZIKV infection, the authors treated type I interferon receptor (IFNAR) deficient mice with ZIKV, and mapped the peptides inducing H-2^b-restricted CD8⁺ T cell response. Results showed that 26 and 15 CD8⁺ T cell-reactive peptides were identified and validated for ZIKV African (MR766) and Asian (FSS13025) strains, respectively. Moreover, CD8⁺ T cells mainly targeted viral prM, E and NS5 proteins, and were polyfunctional especially cytotoxic in infected mice. Furthermore, adoptive transfer of ZIKV-immunized CD8⁺ T cells into infected mice reduced its viral burden in serum and brain. Besides, CD8⁺ T cell-deficient mice resulted in higher mortality in ZIKV infection. In conclusion, these results demonstrate the protective role of CD8⁺T cells against ZIKV infection in IFNAR deficient mice, and this study provides a T cell competent mouse model for further investigation of ZIKV-specific T cell responses.

References:

1.         Weiskopf, D., et al. Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8⁺ T cells. Proc. Natl. Acad. Sci. USA. 2013. 10, E2046–E2053.

2.         Diamond, M.S., et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J. Exp. Med. 2011. 208, 1989–2003.