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寨卡病毒感染斑马鱼幼虫视网膜损伤的综述。

Recapitulation of Retinal Damage in Zebrafish Larvae Infected with Zika Virus.

机构信息

Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, São Paulo 05503-900, Brazil.

Laboratory of Neuropharmacological Studies (LABEN), Post-Graduation Program of Pharmaceutical Science, Federal University of Sergipe, São Paulo 05503-009, Brazil.

出版信息

Cells. 2022 Apr 26;11(9):1457. doi: 10.3390/cells11091457.

Abstract

Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen-host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus.

摘要

斑马鱼正越来越多地被用作研究传染病和深入了解病原体-宿主相互作用的模型。在这里,我们利用斑马鱼重现先天性 ZIKV 感染,并首次证明它可用于模拟感染和再感染,并监测抗病毒和炎症免疫反应,以及胚胎发育过程中的大脑生长和眼睛异常。通过将巴西 ZIKV 株注射到单细胞期胚胎的卵黄囊中,我们证实,72 小时后,ZIKV 成功感染了幼虫,受病毒感染的宿主的身体状况包括存活胚胎的明显形态变化(84%),表现为头大小减小和视网膜损伤,其特征是晶状体和内核层厚度增加。运动活动的变化和无法感知视觉刺激是由 ZIKV 引起的视网膜形态变化引起的。此外,我们还证明了 ZIKV 在斑马鱼幼虫中的复制能力和对新的健康幼虫的感染能力,损害了它们的视觉和神经功能。这些数据强化了 ZIKV 在大脑和视觉结构中的有害活性,并确立了斑马鱼作为研究病毒病理学相关分子机制的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f53/9100881/ce3a4812e3c0/cells-11-01457-g001.jpg

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