For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

中文翻译：

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登革热病毒抗体增强寨卡病毒感染。

几十年来，人类感染寨卡病毒（ZIKV）（一种蚊子传播的黄病毒）是偶发性的，与轻度疾病有关，并且由于症状与其他急性发热性疾病相似，因此未被报道。与ZIKV相关的严重疾病的最新报道大大提高了人们的认识。预计ZIKV将继续在美洲和全球发现有感染伊蚊的媒介。登革热病毒（DENV）是最常见的蚊子传播的人类黄病毒，在最近的ZIKV引入领域中既有根深蒂固，又是爆发的源头。DENV和ZIKV密切相关，导致大量抗原重叠。通过抗体依赖性增强（ADE），抗DENV抗体可以增强DENV对某些类型的免疫细胞的感染力，导致与严重疾病结果相关的病毒产生增加。类似地，已显示ZIKV对其他黄病毒产生的抗体产生ADE反应。我们使用中和和ADE试验测试了表征良好的广泛中和的人抗DENV单克隆抗体（HMAb）和人DENV免疫血清对ZIKV的中和和增强潜力。我们显示抗DENV HMAbs交叉反应，不会中和，并在体外大大增强ZIKV感染。DENV免疫血清对ZIKV具有不同程度的中和作用，并同样增强ZIKV感染。我们的结果表明，预先存在的DENV免疫可能增强体内ZIKV感染，并可能导致疾病严重程度增加。