Division of Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA, 70433, USA.
Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, 70433, USA.
Brain Pathol. 2020 Nov;30(6):1017-1027. doi: 10.1111/bpa.12873. Epub 2020 Jul 21.
Zika virus (ZIKV) is a flavivirus that can cause neuropathogenesis in adults and fetal neurologic malformation following the infection of pregnant women. We used a nonhuman primate model, the Indian-origin Rhesus macaque (IRM), to gain insight into virus-associated hallmarks of ZIKV-induced adult neuropathology. We find that the virus causes prevalent acute and chronic neuroinflammation and chronic disruption of the blood-brain barrier (BBB) in adult animals. ZIKV infection resulted in specific short- and long-term augmented expression of the chemokine CXCL12 in the central nervous system (CNS)of adult IRMs. Moreover, CXCL12 expression persists long after the initial viral infection is apparently cleared. CXCL12 plays a key role both in regulating lymphocyte trafficking through the BBB to the CNS and in mediating repair of damaged neural tissue including remyelination. Understanding how CXCL12 expression is controlled will likely be of central importance in the definition of ZIKV-associated neuropathology in adults.
Zika 病毒（ZIKV）是一种黄病毒，可导致孕妇感染后成人神经病变和胎儿神经畸形。我们使用了一种非人类灵长类动物模型，即印度起源的恒河猴（IRM），以深入了解 ZIKV 引起成人神经病理学的相关病毒特征。我们发现该病毒可引起成年动物普遍存在的急性和慢性神经炎症，以及慢性血脑屏障（BBB）破坏。ZIKV 感染导致成年 IRM 中枢神经系统（CNS）中趋化因子 CXCL12 的短期和长期表达增加。此外，在最初的病毒感染明显清除后，CXCL12 的表达仍持续很长时间。CXCL12 在调节淋巴细胞通过 BBB 向 CNS 的迁移以及介导受损神经组织的修复（包括髓鞘再生）方面发挥着关键作用。了解 CXCL12 表达是如何受到控制的，对于明确成人 ZIKV 相关神经病理学可能具有重要意义。
