Proteome and ubiquitinome analyses of the brain cortex in K18- hACE2 mice infected with SARS-CoV-2

Qiaochu Wang; Wanjun Peng; Yehong Yang; Yue Wu; Rong Han; Tao Ding; Xutong Zhang; Jiangning Liu; Juntao Yang; Jiangfeng Liu

doi:10.1016/j.isci.2024.110602

Proteome and ubiquitinome analyses of the brain cortex in K18- hACE2 mice infected with SARS-CoV-2

iScience. 2024 Jul 27;27(9):110602. doi: 10.1016/j.isci.2024.110602. eCollection 2024 Sep 20.

Authors

Affiliations

¹ 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.
² 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.

Abstract

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-hACE2 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-hACE2 mice, laying the groundwork for further investigation into the pathogenic processes and treatment options for neurological dysfunction following SARS-CoV-2 infection.

Keywords: Molecular biology; Neuroscience; Omics; Proteomics; Virology.