Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS Pathog. 2019 Aug 1;15(8):e1007766. doi: 10.1371/journal.ppat.1007766. eCollection 2019 Aug.
Zika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.
寨卡病毒（ZIKV）和登革热病毒（DENV）是基因和抗原相关的黄病毒，目前在世界上许多热带和亚热带地区流行。2015 年和 2016 年，ZIKV 在美洲的迅速出现，以及最近与格林-巴利综合征、出生缺陷和胎儿丢失的关联，导致了这样一种假设，即 DENV 感染诱导交叉反应性抗体，影响继发 ZIKV 感染的严重程度。也有人提出，预先存在的 ZIKV 免疫可能影响 DENV 的发病机制。我们在三只恒河猴和十五只食蟹猴中检查了继发 ZIKV 感染的结果，以及在另外三只恒河猴中检查了继发 DENV-2 感染的结果，这些动物在原发 ZIKV 感染后一年。尽管所有动物在继发感染前都检测到了交叉结合抗体，一些动物检测到了交叉中和抗体，但先前的 DENV 或 ZIKV 感染对这些动物异质继发感染的临床过程没有明显影响。所有动物都有无症状感染，与对照组相比，血液学参数没有明显改变。大约在原发 ZIKV 感染一年后感染 DENV-2 的恒河猴与感染 DENV-2 的 ZIKV 初免动物的血清 vRNA 载量相比，血浆中的 vRNA 载量更高，但不能排除样本类型的差异影响。在食蟹猴中，原发 DENV 感染的血清型不影响继发 ZIKV 感染的结果。
