Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus.
Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus.
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DOI：
10.1038/ni.3515
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发表时间：
2016-09
影响因子：
30.5
通讯作者：
Screaton GR
中科院分区：
文献类型：
--
作者：
Dejnirattisai W;Supasa P;Wongwiwat W;Rouvinski A;Barba-Spaeth G;Duangchinda T;Sakuntabhai A;Cao-Lormeau VM;Malasit P;Rey FA;Mongkolsapaya J;Screaton GR
寨卡病毒（ZIKV）于1947年被发现，并且被认为会引发相对较轻的疾病。近期寨卡病毒在南美洲的爆发性流行引发了广泛关注，有报告称其神经后遗症包括从吉兰 - 巴雷综合征到小头畸形等多种情况。寨卡病毒感染发生在先前曾有登革热流行的地区，登革热是一种与寨卡病毒密切相关的黄病毒。在此我们研究这两种病毒之间的血清学交叉反应。登革热免疫血浆与寨卡病毒有显著的交叉反应，并可能促使寨卡病毒感染的抗体依赖性增强。通过一组人类抗登革热单克隆抗体，我们发现大多数与登革热包膜蛋白反应的抗体也会与寨卡病毒反应。针对包括免疫显性融合环表位在内的线性表位的抗体虽然能够结合寨卡病毒，但无法中和该病毒，反而促进了抗体依赖性增强作用。这些数据表明，登革热免疫可能促使寨卡病毒更高程度的复制，并且对疾病发病机制以及未来的寨卡病毒和登革热疫苗项目具有明确的影响。
Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern with reports of neurological sequelae ranging from Guillain Barré syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue, a flavivirus closely related to ZIKV. Here we investigate the serological crossreaction between the two viruses. Dengue immune plasma substantially crossreacted with ZIKV and could drive antibody-dependent enhancement of ZIKV infection. Using a panel of human anti-dengue monoclonal antibodies we showed that most antibodies reacting to dengue envelope protein also reacted to ZIKV. Antibodies to linear epitopes including the immunodominant fusion loop epitope while able to bind ZIKV could not neutralize the virus but instead promoted ADE. These data indicate that dengue immunity may drive higher ZIKV replication and have clear implications for disease pathogenesis and future ZIKV and dengue vaccine programs.