寨卡病毒通过抑制干扰素 β 翻译在血管内皮细胞上复制并侵入中枢神经系统。

Zika virus replication on endothelial cells and invasion into the central nervous system by inhibiting interferon β translation.

机构信息

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, China; International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, China.

出版信息

Virology. 2023 May;582:23-34. doi: 10.1016/j.virol.2023.03.006. Epub 2023 Mar 17.

DOI:10.1016/j.virol.2023.03.006

PMID:36996689

Abstract

The blood-brain barrier (BBB) is one of the tightest physical barriers to prevent pathogens from invading the central nervous system (CNS). However, the mechanism by which Zika virus (ZIKV) crossing the BBB remains unresolved. We found ZIKV induced high morbidity and mortality in newborn mice, accompanied by inflammatory injury on CNS. ZIKV was found to replicate primarily in the cortex and hippocampus in neonatal mouse brains. An in vitro model revealed that ZIKV had no impact on hBMECs permeability but led to endothelial activation, as shown by the enhancement of adhesion molecules expression and F-actin redistribution. ZIKV replication in hBMECs might be associated with the suppression of IFN-β translation via inhibiting RPS6 phosphorylation. On the other hand, ZIKV infection induced IFN-stimulated genes (ISGs), activated the mitogen-activated protein kinase (MAPK) signaling pathway, and promoted chemokine secretion. This study provides an understanding of virus replication and transmigration across the BBB during ZIKV infection.

摘要

血脑屏障（BBB）是阻止病原体侵入中枢神经系统（CNS）的最紧密的物理屏障之一。然而，寨卡病毒（ZIKV）穿越 BBB 的机制仍未解决。我们发现 ZIKV 可导致新生小鼠出现高发病率和死亡率，并伴有 CNS 炎症损伤。研究发现，ZIKV 主要在新生小鼠大脑的皮质和海马中复制。体外模型表明，ZIKV 对 hBMECs 的通透性没有影响，但会导致内皮细胞激活，表现为黏附分子表达和 F-actin 重分布增强。ZIKV 在 hBMECs 中的复制可能与通过抑制 RPS6 磷酸化来抑制 IFN-β 翻译有关。另一方面，ZIKV 感染诱导 IFN 刺激基因（ISGs），激活丝裂原活化蛋白激酶（MAPK）信号通路，并促进趋化因子的分泌。本研究有助于了解 ZIKV 感染期间病毒在 BBB 中的复制和迁移。