Department of Neuroscience, Del Monte Institute of Neuroscience, University of Rochester, URMC, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
Department of Imaging Sciences, University of Rochester, URMC, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
Commun Biol. 2021 Nov 22;4(1):1318. doi: 10.1038/s42003-021-02856-x.
While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it's unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it's unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes.
虽然在严重感染 COVID-19 的患者中存在 SARS-CoV-2 多器官嗜性,但目前尚不清楚这种情况是否发生在健康的年轻人中。此外,对于针对刺突蛋白 (SP) 的抗体,目前尚不清楚这些抗体是否同样能降低 SARS-CoV-2/SP 多器官嗜性。我们使用荧光标记的 SP-NIRF 来研究病毒行为,使用体内动态成像系统和体外组织分析,在年轻小鼠中进行研究。我们发现 SP 全身分布,随后缓慢区域性消除,除肝脏外,肝脏出现积累。SP 摄取量最高的是肺部,其次是肾脏、心脏和肝脏,但与脉络丛不同,它未在脑实质或 CSF 中检测到。因此,在年轻健康的小鼠中,脑血管屏障有效地限制了 SP 进入脑实质。虽然抗 ACE2 和抗 SP 抗体均能抑制 SP 的分布和器官摄取,但抗 SP 抗体的效果更好。由此可以推断,这些抗体对 SARS-CoV-2 多器官嗜性具有疗效,这可能决定 COVID-19 的器官特异性结局。