Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.

Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.
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DOI:
10.1016/j.celrep.2016.08.079
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发表时间:
2016-09-20
期刊:
影响因子:
8.8
通讯作者:
Apte RS
Apte RS
中科院分区:
生物学1区
文献类型:
--
作者:
Miner JJ;Sene A;Richner JM;Smith AM;Santeford A;Ban N;Weger-Lucarelli J;Manzella F;Rückert C;Govero J;Noguchi KK;Ebel GD;Diamond MS;Apte RS

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寨卡病毒(ZIKV)是一种引起先天性畸形和格林-巴利综合征的新出现的黄病毒。ZIKV感染还导致严重的眼部疾病,其特征在于新生儿的视神经炎、脉络膜视网膜萎缩和失明以及成人的结膜炎和葡萄膜炎。我们使用最近开发的发病机制的小鼠模型评估了眼睛的ZIKV感染。ZIKV接种的小鼠发生结膜炎、全葡萄膜炎和角膜、虹膜、视神经以及视网膜中的神经节细胞和双极细胞的感染。这种表型与进入受体Axl或Mertk无关,因为Axl−/−、Mertk−/−或Axl−/− Mertk−/− DKO小鼠的感染水平与对照动物相似。我们还在泪液中检测到丰富的病毒RNA,表明病毒可能从泪腺分泌或从角膜脱落。该模型为研究ZIKV诱导的眼部疾病、定义病毒持续存在的机制以及开发眼部病毒感染的治疗方法提供了基础。
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 using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, pan-uveitis and infection of the cornea, iris, optic nerve, and the ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, as Axl−/−, Mertk−/− or Axl−/− Mertk−/− DKO mice sustained similar levels of infection as control animals. We also detected abundant viral RNA in tears, suggesting that virus may 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.
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