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Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection
Viruses ( IF 5.818 ) Pub Date : 2021-09-14 , DOI: 10.3390/v13091823
Vidhya Munnamalai 1, 2 , Nabilah H Sammudin 3 , Caryl A Young 1 , Ankita Thawani 3 , Richard J Kuhn 3, 4 , Donna M Fekete 3, 4, 5
Affiliation  

Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions; this test screens for hearing loss originating in the cochlea. This observation leads to the question of whether mammalian cochlear tissues are susceptible to infection by ZIKV during development. To address this question using a mouse model, the sensory cochlea was explanted at proliferative, newly post-mitotic or maturing stages. ZIKV was added for the first 24 h and organs cultured for up to 6 days to allow for cell differentiation. Results showed that ZIKV can robustly infect proliferating sensory progenitors, as well as post-mitotic hair cells and supporting cells. Virus neutralization using ZIKV-117 antibody blocked cochlear infection. AXL is a cell surface molecule known to enhance the attachment of flavivirus to host cells. While Axl mRNA is widely expressed in embryonic cochlear tissues susceptible to ZIKV infection, it is selectively downregulated in the post-mitotic sensory organ by E15.5, even though these cells remain infectible. These findings may offer insights into which target cells could potentially contribute to hearing loss resulting from fetal exposure to ZIKV in humans.

中文翻译:

胚胎和新生小鼠耳蜗易感染寨卡病毒

先天性寨卡综合征 (CZS) 是由寨卡病毒 (ZIKV) 垂直传播至妊娠人类胎儿引起的。一部分 CZS 小头畸形婴儿耳声发射减少;该测试筛查源自耳蜗的听力损失。这一观察结果引发了哺乳动物耳蜗组织在发育过程中是否易受 ZIKV 感染的问题。为了使用小鼠模型解决这个问题,在增殖期、新的有丝分裂后或成熟期移植了感觉耳蜗。在前 24 小时添加 ZIKV,器官培养长达 6 天以允许细胞分化。结果表明,ZIKV 可以强烈感染增殖的感觉祖细胞,以及有丝分裂后的毛细胞和支持细胞。使用 ZIKV-117 抗体中和病毒可阻断耳蜗感染。AXL 是一种细胞表面分子,已知可增强黄病毒对宿主细胞的附着。尽管Axl mRNA 在易受 ZIKV 感染的胚胎耳蜗组织中广泛表达,它在有丝分裂后的感觉器官中被 E15.5 选择性下调,即使这些细胞仍然是可感染的。这些发现可能有助于深入了解哪些靶细胞可能导致胎儿因人类 ZIKV 暴露而导致听力损失。
更新日期:2021-09-14
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