SARS-CoV-2 tropism in the brain and its relationship to COVID-19 pathogenesis

COVID-19是一场美国和全球灾难，已导致近100万人死亡 其中包括203，000多名美国人。COVID-19是由一部小说引起的 称为严重急性呼吸综合征（SARS）-CoV-2的β-冠状病毒（CoV）， 据报道会导致严重的肺炎和致命的呼吸衰竭。之甚少 了解这种病毒的致病机理及其致病机制。在这 应用，我们建议测试SARS-CoV-2对大脑的影响。我们将开发 表达SARS-CoV-2受体的多细胞类型特异性小鼠模型，人 ACE 2，以细胞类型特异性方式。然后我们将使用各种分子， 生物化学，组织学和神经科学方法来测试大脑的向性， SARS-CoV-2的深度及其对呼吸中枢调节的影响。 该提案将对我们目前对COVID的理解产生变革性影响- 19及其发病机制，并将揭示重要的治疗靶点。

COVID-19 is a US and global disaster which has led to the deaths of almost a million individuals, including over 203,000 Americans, thus far. COVID-19 is caused by a novel beta-coronavirus (CoV) known as Severe Acute Respiratory Syndrome (SARS)-CoV-2, which was reported to cause severe pneumonia and lethal respiratory failure. Little is known about the disease mechanism of this virus and its disease mechanism. In this application, we propose to test the effects of SARS-CoV-2 on the brain. We will develop multiple cell-type specific mouse models that express the SARS-CoV-2 receptor, human ACE2, in a cell-type specific manner. We will then use a variety of molecular, biochemical, histological and neuroscience approaches to test the brain tropism of SARS-CoV-2 in depth and the effects of that on the central regulation of respiration. This proposal will have a transformative impact on our current understanding of COVID- 19 and its mechanisms of pathogenesis and will uncover important therapeutic targets.