Bardina Susana V, Bunduc Paul, Tripathi Shashank, Duehr James, Frere Justin J, Brown Julia A, Nachbagauer Raffael, Foster Gregory A, Krysztof David, Tortorella Domenico, Stramer Susan L, García-Sastre Adolfo, Krammer Florian, Lim Jean K
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Science. 2017 Apr 14;356(6334):175-180. doi: 10.1126/science.aal4365. Epub 2017 Mar 30.
Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity-including fever, viremia, and viral loads in spinal cord and testes-and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.
寨卡病毒（ZIKV）正在迅速传播到世界上其他黄病毒流行的地区，如登革热病毒（DENV）和西尼罗河病毒（WNV）的流行地区。抗体依赖性增强作用与更严重形式的黄病毒疾病有关，但这是否也适用于寨卡病毒感染尚不清楚。使用来自登革热病毒和西尼罗河病毒感染个体的恢复期血浆，我们发现体外寨卡病毒感染有显著增强，这是通过免疫球蛋白G与Fcγ受体的结合介导的。将登革热病毒或西尼罗河病毒恢复期血浆注射到易感染寨卡病毒的小鼠体内，导致发病率增加，包括发热、病毒血症以及脊髓和睾丸中的病毒载量增加，死亡率也增加。抗体依赖性增强作用可能解释了与近期寨卡病毒爆发相关的严重疾病表现，并突出了在设计黄病毒疫苗时需格外谨慎的必要性。
