Wang Qiaochu, Peng Wanjun, Yang Yehong, Wu Yue, Han Rong, Ding Tao, Zhang Xutong, Liu Jiangning, Yang Juntao, Liu Jiangfeng
State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, CAMS and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China.
iScience. 2024 Jul 27;27(9):110602. doi: 10.1016/j.isci.2024.110602. eCollection 2024 Sep 20.
Clinical research indicates that SARS-CoV-2 infection is linked to several neurological consequences, and the virus is still spreading despite the availability of vaccinations and antiviral medications. To determine how hosts respond to SARS-CoV-2 infection, we employed LC-MS/MS to perform ubiquitinome and proteome analyses of the brain cortexes from K18- mice in the presence and absence of SARS-CoV-2 infection. A total of 8,024 quantifiable proteins and 5,220 quantifiable lysine ubiquitination (Kub) sites in 2023 proteins were found. Glutamatergic synapse, calcium signaling pathway, and long-term potentiation may all play roles in the neurological consequences of SARS-CoV-2 infection. Then, we observed possible interactions between 26 SARS-CoV-2 proteins/E3 ubiquitin-protein ligases/deubiquitinases and several differentially expressed mouse proteins or Kub sites. We present the first description of the brain cortex ubiquitinome in K18- mice, laying the groundwork for further investigation into the pathogenic processes and treatment options for neurological dysfunction following SARS-CoV-2 infection.
临床研究表明，新型冠状病毒2（SARS-CoV-2）感染与多种神经学后果相关，尽管有疫苗和抗病毒药物，但该病毒仍在传播。为了确定宿主对SARS-CoV-2感染的反应，我们采用液相色谱-串联质谱法（LC-MS/MS），对感染和未感染SARS-CoV-2的K18-小鼠的大脑皮层进行泛素组和蛋白质组分析。共发现了8024种可定量蛋白质以及2023种蛋白质中的5220个可定量赖氨酸泛素化（Kub）位点。谷氨酸能突触、钙信号通路和长时程增强可能都在SARS-CoV-2感染的神经学后果中起作用。然后，我们观察了26种SARS-CoV-2蛋白/E3泛素蛋白连接酶/去泛素化酶与几种差异表达的小鼠蛋白或Kub位点之间可能的相互作用。我们首次描述了K18-小鼠大脑皮层的泛素组，为进一步研究SARS-CoV-2感染后神经功能障碍的致病过程和治疗方案奠定了基础。
