Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Cell Rep. 2020 Apr 28;31(4):107569. doi: 10.1016/j.celrep.2020.107569.
Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus responsible for recent epidemics across the Americas, and it is closely related to dengue virus (DENV). Here, we study samples from 46 DENV-naive and 43 DENV-immune patients with RT-PCR-confirmed ZIKV infection at early-acute, late-acute, and convalescent time points from our pediatric cohort study in Nicaragua. We analyze the samples via RNA sequencing (RNA-seq), CyTOF, and multiplex cytokine/chemokine Luminex to generate a comprehensive, innate immune profile during ZIKV infection. Immunophenotyping and analysis of cytokines/chemokines reveal that CD14 monocytes play a key role during ZIKV infection. Further, we identify CD169 (Siglec-1) on CD14 monocytes as a potential biomarker of acute ZIKV infection. Strikingly distinct transcriptomic and immunophenotypic signatures are observed at all three time points. Interestingly, pre-existing dengue immunity has minimal impact on the innate immune response to Zika. Finally, this comprehensive immune profiling and network analysis of ZIKV infection in children serves as a valuable resource.
寨卡病毒（ZIKV）是一种新兴的虫媒黄病毒，导致美洲近期爆发疫情，与登革热病毒（DENV）密切相关。在此，我们研究了来自尼加拉瓜儿科队列研究中 46 名初次感染 DENV 的患者和 43 名初次感染 DENV 的患者的样本，这些患者的 ZIKV 感染通过 RT-PCR 确诊。我们通过 RNA 测序（RNA-seq）、CyTOF 和多重细胞因子/趋化因子 Luminex 分析样本，生成 ZIKV 感染期间全面的固有免疫特征。免疫表型和细胞因子/趋化因子分析表明，CD14 单核细胞在 ZIKV 感染中发挥关键作用。此外，我们确定 CD14 单核细胞上的 CD169（Siglec-1）是急性 ZIKV 感染的潜在生物标志物。在所有三个时间点均观察到明显不同的转录组和免疫表型特征。有趣的是，先前存在的登革热免疫力对寨卡病毒的固有免疫反应影响很小。最后，该研究对儿童 ZIKV 感染的全面免疫特征分析和网络分析为这一疾病提供了有价值的资源。
