Fetal brain vulnerability to SARS-CoV-2 infection.
Fetal brain vulnerability to SARS-CoV-2 infection.
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DOI：
10.1016/j.bbi.2023.06.015
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发表时间：
2023-08
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影响因子：
--
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中科院分区：
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SARS-CoV-2 在产前感染期间是否可以从母亲传染给胎儿一直存在争议。然而，最近的证据，例如脐带血和羊水中的病毒RNA检测，以及胎儿组织中其他进入受体的发现，表明病毒有可能传播到胎儿并感染胎儿。此外，在后期发育过程中接触母体 COVID-19 的新生儿表现出神经发育和运动技能缺陷，这表明可能会在子宫内发生继发的神经感染或炎症。因此，我们使用人类 ACE2 敲入小鼠研究了 SARS-CoV-2 的传播潜力以及感染对发育中大脑的影响。在这个模型中，我们发现病毒传播到胎儿组织（包括大脑）发生在发育后期，并且感染主要针对男性胎儿。在大脑中，SARS-CoV-2 感染主要发生在脉管系统内，但也发生在其他细胞内，如神经元、神经胶质细胞和脉络丛细胞；然而，在胎儿组织中没有观察到病毒复制和细胞死亡增加。有趣的是，在感染和模拟感染的后代之间观察到早期总体发育差异，并且在初次感染后 7 天，在受感染的大脑中观察到高水平的神经胶质增生，尽管此时病毒已被清除。在怀孕小鼠中，与非怀孕小鼠相比，我们还观察到更严重的 COVID-19 感染，体重减轻更严重，病毒传播到大脑的情况也更严重。令人惊讶的是，尽管表现出疾病的临床症状，但我们没有观察到这些受感染小鼠的母体炎症或抗病毒干扰素反应增加。总体而言，这些发现对产前接触 COVID-19 后母亲的神经发育和妊娠并发症具有令人担忧的影响。
Whether or not SARS-CoV-2 can cross from mother to fetus during a prenatal infection has been controversial; however, recent evidence such as viral RNA detection in umbilical cord blood and amniotic fluid, as well as the discovery of additional entry receptors in fetal tissues suggests a potential for viral transmission to and infection of the fetus. Furthermore, neonates exposed to maternal COVID-19 during later development have displayed neurodevelopmental and motor skill deficiencies, suggesting the potential for consequential neurological infection or inflammation in utero. Thus, we investigated transmission potential of SARS-CoV-2 and the consequences of infection on the developing brain using human ACE2 knock-in mice. In this model, we found that viral transmission to the fetal tissues, including the brain, occurred at later developmental stages, and that infection primarily targeted male fetuses. In the brain, SARS-CoV-2 infection largely occurred within the vasculature, but also within other cells such as neurons, glia, and choroid plexus cells; however, viral replication and increased cell death were not observed in fetal tissues. Interestingly, early gross developmental differences were observed between infected and mock-infected offspring, and high levels of gliosis were seen in the infected brains 7 days post initial infection despite viral clearance at this time point. In the pregnant mice, we also observed more severe COVID-19 infections, with greater weight loss and viral dissemination to the brain, compared to non-pregnant mice. Surprisingly, we did not observe an increase in maternal inflammation or the antiviral IFN response in these infected mice, despite showing clinical signs of disease. Overall, these findings have concerning implications regarding neurodevelopment and pregnancy complications of the mother following prenatal COVID-19 exposure.
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DOI：
10.1073/pnas.2122236119
发表时间：
2022-07-26
影响因子：
11.1
作者：
通讯作者：
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影响因子：
48
作者：
Bazarian, Jeffrey J.;Biberthaler, Peter;Jagoda, Andy S.
通讯作者：
Jagoda, Andy S.
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
9.3
作者：
Cardoso FL;Herz J;Fernandes A;Rocha J;Sepodes B;Brito MA;McGavern DB;Brites D
通讯作者：
Brites D
DOI：
10.1093/cid/cit045
发表时间：
2013-05
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Richards JL;Hansen C;Bredfeldt C;Bednarczyk RA;Steinhoff MC;Adjaye-Gbewonyo D;Ault K;Gallagher M;Orenstein W;Davis RL;Omer SB
通讯作者：
Omer SB