Department of Molecular Medicine, University of Padova, 35121 Padova, Italy.
Viral Zoonoses, Emerging and Vector-Borne Infections Group, Institute of Virology, University of Veterinary Medicine, 1210 Vienna, Austria.
Viruses. 2020 Aug 12;12(8):882. doi: 10.3390/v12080882.
West Nile virus (WNV) and Usutu virus (USUV) are genetically related neurotropic mosquito-borne flaviviruses, which frequently co-circulate in nature. Despite USUV seeming to be less pathogenic for humans than WNV, the clinical manifestations induced by these two viruses often overlap and may evolve to produce severe neurological complications. The aim of this study was to investigate the effects of WNV and USUV infection on human induced pluripotent stem cell-derived neural stem cells (hNSCs), as a model of the neural progenitor cells in the developing fetal brain and in adult brain. Zika virus (ZIKV), a flavivirus with known tropism for NSCs, was used as the positive control. Infection of hNSCs and viral production, effects on cell viability, apoptosis, and innate antiviral responses were compared among viruses. WNV displayed the highest replication efficiency and cytopathic effects in hNSCs, followed by USUV and then ZIKV. In these cells, both WNV and USUV induced the overexpression of innate antiviral response genes at significantly higher levels than ZIKV. Expression of interferon type I, interleukin-1β and caspase-3 was significantly more elevated in WNV- than USUV-infected hNSCs, in agreement with the higher neuropathogenicity of WNV and the ability to inhibit the interferon response pathway.
西尼罗河病毒（WNV）和乌苏图病毒（USUV）是具有遗传相关性的亲神经性蚊媒黄病毒，它们经常在自然界中共同循环。尽管 USUV 似乎对人类的致病性比 WNV 低，但这两种病毒引起的临床表现经常重叠，并可能发展为产生严重的神经并发症。本研究旨在研究 WNV 和 USUV 感染对人诱导多能干细胞源性神经干细胞（hNSC）的影响，hNSC 是发育中胎儿大脑和成年大脑中的神经祖细胞的模型。具有已知 NSCs 趋向性的黄病毒寨卡病毒（ZIKV）被用作阳性对照。比较了病毒之间 hNSC 的感染和病毒产生、对细胞活力、细胞凋亡和先天抗病毒反应的影响。WNV 在 hNSC 中的复制效率和细胞病变效应最高，其次是 USUV，然后是 ZIKV。在这些细胞中，WNV 和 USUV 诱导的先天抗病毒反应基因的表达水平均明显高于 ZIKV。WNV 感染的 hNSC 中干扰素 I 型、白细胞介素 1β 和半胱氨酸天冬氨酸蛋白酶 3 的表达明显升高，这与 WNV 的更高神经致病性和抑制干扰素反应途径的能力一致。
