SARS-CoV-2 infects human adult donor eyes and hESC-derived ocular epithelium.

SARS-CoV-2 infects human adult donor eyes and hESC-derived ocular epithelium.
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DOI:
10.1016/j.stem.2021.04.028
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发表时间:
2021-07-01
期刊:
影响因子:
23.9
通讯作者:
Blenkinsop TA
Blenkinsop TA
中科院分区:
医学1区
文献类型:
--
作者:
Eriksen AZ;Møller R;Makovoz B;Uhl SA;tenOever BR;Blenkinsop TA

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SARS-CoV-2大流行造成了前所未有的全球行为中断和重大生命损失。为了最大限度地减少SARS-CoV-2的传播,从所有可能的进入途径了解感染机制是至关重要的。虽然气溶胶传播被认为是主要的传播途径,但已在眼液中检测到病毒颗粒,这表明眼睛可能是病毒进入的易损点。为此,我们确认了SARS-CoV-2进入因子和抗原在死后新冠肺炎患者眼表组织中的表达,并在身体样本和眼器官培养中观察到病毒的有效复制,最明显的是在角膜缘区域。体外感染的眼表细胞和人胚胎干细胞来源的眼培养物的转录分析显示,在感染的细胞中,NF-κB的诱导很强,并且I/III型干扰素信号减弱。总而言之,这些数据表明,眼睛可以直接感染SARS-CoV-2,并暗示角膜缘是病毒进入的门户。Eriksen等人。结果表明,新冠肺炎患者样本中有SARS-CoV-2抗原的表达,并发现身体眼表细胞有很强的感染能力。来自人类供体的角膜缘细胞和hPSC全眼分化模型似乎更容易感染,表现出强大的趋化因子产生和受损的干扰素-I/-III反应。
The SARS-CoV-2 pandemic has caused unparalleled disruption of global behavior and significant loss of life. To minimize SARS-CoV-2 spread, understanding the mechanisms of infection from all possible routes of entry is essential. While aerosol transmission is thought to be the primary route of spread, viral particles have been detected in ocular fluid, suggesting that the eye may be a vulnerable point of viral entry. To this end, we confirmed SARS-CoV-2 entry factor and antigen expression in post-mortem COVID-19 patient ocular surface tissue and observed productive viral replication in cadaver samples and eye organoid cultures, most notably in limbal regions. Transcriptional analysis of ex vivo infected ocular surface cells and hESC-derived eye cultures revealed robust induction of NF-κB in infected cells as well as diminished type I/III interferon signaling. Together these data suggest that the eye can be directly infected by SARS-CoV-2 and implicate limbus as a portal for viral entry. Eriksen et al. show that SARS-CoV-2 antigens are expressed in COVID-19 patient samples and find robust infection of cadaveric ocular surface cells. Limbus cells derived from human donors and a hPSC whole-eye differentiation model seem more prone to infection and exhibit robust chemokine production and an impaired IFN-I/-III response.
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