Miner Jonathan J, Sene Abdoulaye, Richner Justin M, Smith Amber M, Santeford Andrea, Ban Norimitsu, Weger-Lucarelli James, Manzella Francesca, Rückert Claudia, Govero Jennifer, Noguchi Kevin K, Ebel Gregory D, Diamond Michael S, Apte Rajendra S
Department of Medicine, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Department of Ophthalmology and Visual Sciences, School of Medicine, Washington University, Saint Louis, MO 63110, US.
Cell Rep. 2016 Sep 20;16(12):3208-3218. doi: 10.1016/j.celrep.2016.08.079. Epub 2016 Sep 6.
Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.
寨卡病毒(ZIKV)是一种新出现的黄病毒,可导致先天性异常和吉兰-巴雷综合征。寨卡病毒感染还会引发严重的眼部疾病,其特征为新生儿视神经炎、脉络膜视网膜萎缩和失明,以及成人结膜炎和葡萄膜炎。我们通过使用最近开发的发病机制小鼠模型评估了眼部的寨卡病毒感染情况。接种寨卡病毒的小鼠出现了结膜炎、全葡萄膜炎,以及角膜、虹膜、视神经、视网膜神经节细胞和双极细胞感染。鉴于Axl(-/-)、Mertk(-/-)和Axl(-/-)Mertk(-/-)双敲除小鼠的感染水平与对照动物相似,这种表型与进入受体Axl或Mertk无关。我们还在泪液中检测到大量病毒RNA,这表明病毒可能从泪腺分泌或从角膜脱落。该模型为研究寨卡病毒引起的眼部疾病、确定病毒持续存在的机制以及开发眼部病毒感染的治疗方法奠定了基础。