PDF(Pubmed)
Abstract：
Neurological symptoms associated with COVID-19, acute and long term, suggest SARS-CoV-2 affects both the peripheral and central nervous systems (PNS/CNS). Although studies have shown olfactory and hematogenous invasion into the CNS, coinciding with neuroinflammation, little attention has been paid to susceptibility of the PNS to infection or to its contribution to CNS invasion. Here we show that sensory and autonomic neurons in the PNS are susceptible to productive infection with SARS-CoV-2 and outline physiological and molecular mechanisms mediating neuroinvasion. Our infection of K18-hACE2 mice, wild-type mice, and golden Syrian hamsters, as well as primary peripheral sensory and autonomic neuronal cultures, show viral RNA, proteins, and infectious virus in PNS neurons, satellite glial cells, and functionally connected CNS tissues. Additionally, we demonstrate, in vitro, that neuropilin-1 facilitates SARS-CoV-2 neuronal entry. SARS-CoV-2 rapidly invades the PNS prior to viremia, establishes a productive infection in peripheral neurons, and results in sensory symptoms often reported by COVID-19 patients.
摘要：
与COVID-19相关的神经系统症状，急性和长期，提示SARS-CoV-2影响外周和中枢神经系统（PNS/CNS）。尽管研究显示嗅觉和血源性侵入中枢神经系统，与神经炎症同时发生，人们很少关注PNS对感染的易感性或其对CNS侵袭的贡献。在这里，我们表明PNS中的感觉和自主神经元容易受到SARS-CoV-2的生产性感染，并概述了介导神经侵袭的生理和分子机制。我们感染K18-hACE2小鼠，野生型小鼠,和金色的叙利亚仓鼠，以及主要的外周感觉和自主神经培养，显示病毒RNA，蛋白质，和PNS神经元中的感染性病毒，卫星胶质细胞，和功能性连接的中枢神经系统组织。此外,我们展示，在体外，神经纤毛蛋白-1促进SARS-CoV-2神经元进入。SARS-CoV-2在病毒血症之前迅速侵入PNS，在外周神经元中建立生产性感染，并导致COVID-19患者经常报告的感觉症状。
