Japanese encephalitis virus-primed CD8+ T cells prevent antibody-dependent enhancement of Zika virus pathogenesis
Japanese encephalitis virus-primed CD8+ T cells prevent antibody-dependent enhancement of Zika virus pathogenesis
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日本脑炎病毒引发的 CD8 T 细胞可防止寨卡病毒发病机制的抗体依赖性增强
DOI：
10.1084/jem.20192152
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发表时间：
2020-09-01
影响因子：
15.3
通讯作者：
Wen, Jinsheng
中科院分区：
文献类型：
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作者：
Chen, Dong;Duan, Zhiliang;Wen, Jinsheng
交叉反应性抗黄病毒免疫可影响异源黄病毒感染的结果。然而，在二次寨卡病毒（ZIKV）和日本脑炎病毒（JEV）感染期间，交叉反应性抗体和T细胞之间的相互作用如何使平衡向发病机制或保护作用倾斜尚不清楚。我们发现，接种过JEV的人以及接种JEV的小鼠的血清和IgG与ZIKV发生交叉反应，在转移给小鼠后会加剧致命的ZIKV感染，并且在免疫母鼠所生的幼鼠感染ZIKV时会促进病毒复制和死亡。相比之下，从接触过JEV的小鼠转移CD8(+) T细胞具有保护作用，可降低ZIKV感染小鼠的病毒载量和死亡率，并消除抗体介导的ZIKV感染增强在小鼠中的致死效应。相反，交叉反应性抗ZIKV抗体或CD8(+) T细胞在JEV感染时表现出相同的致病或保护作用，只是母源获得的抗ZIKV抗体对幼鼠的JEV感染没有影响。这些结果为开发安全的抗JEV/ZIKV疫苗提供了线索。
Cross-reactive anti-flaviviral immunity can influence the outcome of infections with heterologous flaviviruses. However, it is unclear how the interplay between cross-reactive antibodies and T cells tilts the balance toward pathogenesis versus protection during secondary Zika virus (ZIKV) and Japanese encephalitis virus (JEV) infections. We show that sera and IgG from JEV-vaccinated humans and JEV-inoculated mice cross-reacted with ZIKV, exacerbated lethal ZIKV infection upon transfer to mice, and promoted viral replication and mortality upon ZIKV infection of the neonates born to immune mothers. In contrast, transfer of CD8(+) T cells from JEV-exposed mice was protective, reducing the viral burden and mortality of ZIKV-infected mice and abrogating the lethal effects of antibody-mediated enhancement of ZIKV infection in mice. Conversely, cross-reactive anti-ZIKV antibodies or CD8(+) T cells displayed the same pathogenic or protective effects upon JEV infection, with the exception that maternally acquired anti-ZIKV antibodies had no effect on JEV infection of the neonates. These results provide clues for developing safe anti-JEV/ZIKV vaccines.