CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
China National Center for Bioinformation, Beijing, 100101, China.
Protein Cell. 2022 Dec;13(12):920-939. doi: 10.1007/s13238-022-00915-5. Epub 2022 Apr 4.
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
SARS-CoV-2 感染导致复杂的临床表现和多种器官损伤,但潜在机制,特别是不同器官中的免疫反应,仍不清楚。在这项研究中,分析了感染 SARS-CoV-2 的恒河猴 14 种组织的综合转录组改变。与正常对照组相比,SARS-CoV-2 感染导致涉及各种检查组织/器官不同功能的基因失调,大脑皮层和右心室的转录组变化明显。有趣的是,大脑皮层表现出明显的炎症反应状态,炎症反应相关基因显著上调。同时,大脑皮层中的凝血、血管生成和纤维化因子的表达也上调。基于我们的发现,SARS-CoV-2 的受体神经纤毛蛋白 1(NRP1)在感染后大脑皮层中显著升高,伴随着炎症因子的释放和组织间信号转导的活跃免疫反应,以正反馈的方式增强了中枢神经系统(CNS)的感染,导致病毒性脑炎。总的来说,我们的研究描绘了 SARS-CoV-2 早期感染恒河猴的多组织/器官转录组图谱,并为 COVID-19 相关临床并发症的机制基础提供了重要见解。