ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects.
ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects.
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DOI：
10.1097/j.pain.0000000000002051
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发表时间：
2020-11
期刊：
影响因子：
7.4
通讯作者：
Price TJ
中科院分区：
文献类型：
--
作者：
Shiers S;Ray PR;Wangzhou A;Sankaranarayanan I;Tatsui CE;Rhines LD;Li Y;Uhelski ML;Dougherty PM;Price TJ
SARS-CoV-2引发了一场全球性危机。COVID-19是由该病毒引起的疾病，其特征是肺炎、呼吸窘迫和高凝状态，可能是致命的。感染的早期症状是嗅觉、味觉和化学感觉丧失。这种疾病的其他神经系统影响已经被描述，但没有解释。现在很明显，许多这些神经系统的影响（例如关节疼痛和头痛）可以在感染后持续至少几个月，这表明感觉神经元参与了持续性疾病。我们发现，人背根神经节（DRG）神经元表达SARS-CoV-2受体，血管紧张素转换酶2在RNA和蛋白质水平。我们还证明，SARS-CoV-2和冠状病毒相关的因子和受体广泛表达的人背根神经节在腰椎和胸部的水平作为评估批量RNA测序。ACE2 mRNA由表达MRGPRD mRNA的伤害感受器亚群表达，表明SARS-CoV-2可能通过进入在皮肤和管腔器官的最外层形成游离神经末梢的神经元而进入神经系统。因此，DRG感觉神经元是SARS-CoV-2入侵周围神经系统的潜在靶点，病毒感染人类伤害感受器可能会导致COVID-19中所见的一些持续性神经学效应。
SARS-CoV-2 has created a global crisis. COVID-19, the disease caused by the virus, is characterized by pneumonia, respiratory distress, and hypercoagulation and can be fatal. An early sign of infection is loss of smell, taste, and chemesthesis—loss of chemical sensation. Other neurological effects of the disease have been described, but not explained. It is now apparent that many of these neurological effects (for instance joint pain and headache) can persist for at least months after infection, suggesting a sensory neuronal involvement in persistent disease. We show that human dorsal root ganglion (DRG) neurons express the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 at the RNA and protein level. We also demonstrate that SARS-CoV-2 and coronavirus-associated factors and receptors are broadly expressed in human DRG at the lumbar and thoracic level as assessed by bulk RNA sequencing. ACE2 mRNA is expressed by a subset of nociceptors that express MRGPRD mRNA, suggesting that SARS-CoV-2 may gain access to the nervous system through entry into neurons that form free nerve endings at the outermost layers of skin and luminal organs. Therefore, DRG sensory neurons are a potential target for SARS-CoV-2 invasion of the peripheral nervous system, and viral infection of human nociceptors may cause some of the persistent neurological effects seen in COVID-19.
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