Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus
Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus
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DOI：
10.1073/pnas.1607931113
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发表时间：
2016-07-12
影响因子：
11.1
通讯作者：
Wrammert, Jens
中科院分区：
文献类型：
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作者：
Priyamvada, Lalita;Quicke, Kendra M.;Wrammert, Jens
寨卡病毒（ZIKV）是一种新出现的蚊媒黄病毒，具有重大的公共卫生问题。ZIKV与其他黄病毒（包括登革病毒（DENV））相比具有高度的序列和结构同源性，导致免疫交叉反应性。提高我们目前对这种免疫交叉反应性的程度和特征的理解是重要的，因为ZIKV目前在登革热高度流行的地区传播。为了评估这些密切相关的病毒之间的交叉反应性免疫应答的程度和功能质量，我们测试了来自9名患有针对ZIKV的PCR证实的DENV感染的泰国患者的急性和恢复期血清。所有测试的血清在结合和中和中均与ZIKV交叉反应。为了深入解构观察到的血清交叉反应性，我们还表征了一组DENV特异性成浆细胞衍生的单克隆抗体（mAb）的抗ZIKV活性。所研究的47种DENV反应性mAb中的近一半结合全ZIKV病毒粒子和ZIKV裂解物两者，其中一个子集也中和ZIKV。此外，来自登革热感染患者的血清和mAb两者在体外增强了携带Fc γ受体（Fc γ R）的细胞的ZIKV感染。总之，这些发现表明，对DENV的预先存在的免疫可能影响针对ZIKV的保护性免疫应答。此外，广泛的交叉反应性可能对DENV经历的群体中的ZIKV毒力和疾病严重程度具有影响。
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (Fc gamma R)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.