Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
Department of Reproductive Medicine and.
Clin Infect Dis. 2017 Apr 1;64(7):914-920. doi: 10.1093/cid/ciw878.
The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive.
Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays.
We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1).
Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.
寨卡病毒（ZIKV）的空前再现令世界震惊，有报道称巴西的小头症病例增多。ZIKV 可感染人类神经祖细胞并损害大脑发育。然而，直接证明 ZIKV 感染人类胎儿脑组织的证据仍然难以捉摸。
本研究使用从 9 位供体获得的脑细胞制剂进行了研究。通过流式细胞术检测病毒抗原并结合各种造血细胞表面标志物来评估病毒感染力。通过病毒 RNA 定量来确定病毒复制情况。同时通过基于微珠的免疫分析检测病毒感染的胎儿脑细胞上清液中的细胞因子水平。
我们还表明，ZIKV 感染在造血细胞中特别明显，其中小胶质细胞是主要的靶细胞之一。感染诱导高水平的促炎免疫介质，如白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素 1β（IL-1β）和单核细胞趋化蛋白 1（MCP-1）。
我们的研究结果强调了在先天性 ZIKV 发病机制中小胶质细胞和神经炎症的重要作用。
