Dejnirattisai Wanwisa, Supasa Piyada, Wongwiwat Wiyada, Rouvinski Alexander, Barba-Spaeth Giovanna, Duangchinda Thaneeya, Sakuntabhai Anavaj, Cao-Lormeau Van-Mai, Malasit Prida, Rey Felix A, Mongkolsapaya Juthathip, Screaton Gavin R
Division of Immunology and Inflammation, Department of Medicine, Hammersmith Campus, Imperial College London, UK.
Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand.
Nat Immunol. 2016 Sep;17(9):1102-8. doi: 10.1038/ni.3515. Epub 2016 Jun 23.
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 virus (DENV), a flavivirus closely related to ZIKV. Here we investigated the serological cross-reaction between the two viruses. Plasma immune to DENV showed substantial cross-reaction to ZIKV and was able to drive antibody-dependent enhancement (ADE) of ZIKV infection. Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV.
寨卡病毒（ZIKV）于1947年被发现，曾被认为只会引发相对轻微的疾病。近期寨卡病毒在南美洲的爆发式流行引发了广泛关注，有报告称出现了从吉兰-巴雷综合征到小头畸形等一系列神经后遗症。寨卡病毒感染发生在先前已接触过登革病毒（DENV）的地区，登革病毒是一种与寨卡病毒密切相关的黄病毒。在此，我们研究了这两种病毒之间的血清学交叉反应。对登革病毒免疫的血浆对寨卡病毒表现出显著的交叉反应，并能够驱动寨卡病毒感染的抗体依赖性增强（ADE）。利用一组针对登革病毒的人单克隆抗体（mAb），我们发现大多数与登革病毒包膜蛋白发生反应的抗体也与寨卡病毒发生反应。针对线性表位（包括免疫显性融合环表位）的抗体能够结合寨卡病毒，但无法中和该病毒，反而促进了ADE。我们的数据表明，对登革病毒的免疫力可能会促使寨卡病毒更多地复制，这对疾病发病机制以及未来针对寨卡病毒和登革病毒的疫苗计划具有明确的意义。
