Zika virus (ZIKV) has recently emerged as an important human pathogen due to the strong evidence that it causes disease of the central nervous system, particularly microcephaly and Guillain–Barré syndrome. The pathogenesis of disease, including mechanisms of neuroinvasion, may include both invasion via the blood–brain barrier and via peripheral (including cranial) nerves. Cellular responses to infection are also poorly understood. This study characterizes the in vitro infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). Readouts included infection kinetics, intracellular virus localization, viral persistence and cytokine responses. Although not as high as in Vero cells, viral titres exceeded 104 plaque-forming units (p.f.u.) ml−1 in the endothelial/neuroglial cell types, except hOECs. Despite these substantial titres, a relatively small proportion of neuroglial cells were primarily infected. Immunolabelling of infected cells revealed localization of the ZIKV envelope and NS3 proteins in the cytoplasm; NS3 staining overlapped with that of dsRNA replication intermediate and the endoplasmic reticulum (ER). Infected OECs and endothelial cells produced high levels of pro-inflammatory chemokines. Nevertheless, ZIKV was also able to establish persistent infection in hOEC and hCMEC/D3 cells. Taken together, these results provide basic insights into ZIKV infection of endothelial and neuroglial cells and will form the basis for further study of ZIKV disease mechanisms.

中文翻译：

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关于寨卡病毒感染神经胶质细胞和脑内皮细胞的基本见解。


寨卡病毒（ZIKV）最近已成为一种重要的人类病原体，因为有强有力的证据表明它会导致中枢神经系统疾病，特别是小头畸形和吉兰-巴利综合征。疾病的发病机制，包括神经侵袭的机制，可能包括通过血脑屏障和周围（包括颅）神经的侵袭。人们对细胞对感染的反应也知之甚少。本研究描述了实验室适应的 ZIKV 非洲 MR766 和两种亚洲毒株的体外感染特征：(1) 脑内皮细胞（hCMEC/D3 细胞系）和 (2) 嗅鞘细胞 (OEC)（分布于颅神经 I 和 I 的神经胶质细胞）嗅球；人类和小鼠 OEC 系）与肾上皮细胞（Vero 细胞，其中 ZIKV 感染得到了很好的表征）。读数包括感染动力学、细胞内病毒定位、病毒持久性和细胞因子反应。尽管不如Vero细胞中的那么高，但在内皮/神经胶质细胞类型（hOEC除外）中的病毒滴度超过10 4空斑形成单位（pfu）ml -1 。尽管滴度很高，但主要感染的神经胶质细胞比例相对较小。受感染细胞的免疫标记揭示了 ZIKV 包膜和 NS3 蛋白在细胞质中的定位； NS3 染色与 dsRNA 复制中间体和内质网 (ER) 的染色重叠。受感染的 OEC 和内皮细胞产生高水平的促炎趋化因子。尽管如此，ZIKV 也能够在 hOEC 和 hCMEC/D3 细胞中建立持续感染。 总而言之，这些结果为内皮细胞和神经胶质细胞的 ZIKV 感染提供了基本见解，并将为进一步研究 ZIKV 疾病机制奠定基础。