Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge

被引:114
作者
Wen, Jinsheng [1 ,2 ]
Ngono, Annie Elong [1 ]
Regla-Nava, Jose Angel [1 ]
Kim, Kenneth [1 ]
Gorman, Matthew J. [3 ]
Diamond, Michael S. [3 ]
Shresta, Sujan [1 ,2 ,4 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA
[2] Wenzhou Med Univ, Sch Basic Med Sci, Inst Arboviruses, Wenzhou 325000, Zhejiang, Peoples R China
[3] Washington Univ, Sch Med, Andrew M & Jane M Bursky Ctr Human Immunol & Immu, Dept Med Mol Microbiol Pathol & Immunol, St Louis, MO 63110 USA
[4] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA
关键词
ANTIBODY-DEPENDENT ENHANCEMENT; MOUSE MODEL; INFECTION; RESPONSES; CD4(+); PATHOGENESIS; LYMPHOCYTES; INSIGHTS; DISEASE; NEUTRALIZATION;
D O I
10.1038/s41467-017-01669-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Zika virus (ZIKV) and dengue virus (DENV) are antigenically related flaviviruses that share cross-reactivity in antibody and T cell responses, and co-circulate in increasing numbers of countries. Whether pre-existing DENV immunity can cross-protect or enhance ZIKV infection during sequential infection of the same host is unknown. Here, we show that DENV-immune Ifnar1(-/-) or wild-type C57BL/6 mice infected with ZIKV have cross-reactive immunity to subsequent ZIKV infection and pathogenesis. Adoptive transfer and cell depletion studies demonstrate that DENV-immune CD8(+) T cells predominantly mediate cross-protective responses to ZIKV. In contrast, passive transfer studies suggest that DENV-immune serum does not protect against ZIKV infection. Thus, CD8(+) T cell immunity generated during primary DENV infection can confer protection against secondary ZIKV infection in mice. Further optimization of current DENV vaccines for T cell responses might confer cross-protection and prevent antibody-mediated enhancement of ZIKV infection.
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页数:11
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