Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2

Xu, Gang1; Wu, Yezi1; Xiao, Tongyang1; Qi, Furong1; Fan, Lujie2; Zhang, Shengyuan1; Zhou, Jian1; He, Yanhua3; Gao, Xiang1; Zeng, Hongxiang1; Li, Yunfei1; Zhang, Zheng1,4,5

2022-09-07

10.1038/s41392-022-01156-y

Signal Transduction and Targeted Therapy   Impact Factor & Quartile

2095-9907

2059-3635

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global pandemic that seriously threatens health and socioeconomic development, but the existed antiviral drugs and vaccines still cannot yet halt the spread of the epidemic. Therefore, a comprehensive and profound understanding of the pathogenesis of SARS-CoV-2 is urgently needed to explore effective therapeutic targets. Here, we conducted a multiomics study of SARS-CoV-2-infected lung epithelial cells, including transcriptomic, proteomic, and ubiquitinomic. Multiomics analysis showed that SARS-CoV-2-infected lung epithelial cells activated strong innate immune response, including interferon and inflammatory responses. Ubiquitinomic further reveals the underlying mechanism of SARS-CoV-2 disrupting the host innate immune response. In addition, SARS-CoV-2 proteins were found to be ubiquitinated during infection despite the fact that SARS-CoV-2 itself didn't code any E3 ligase, and that ubiquitination at three sites on the Spike protein could significantly enhance viral infection. Further screening of the E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) library revealed four E3 ligases influencing SARS-CoV-2 infection, thus providing several new antiviral targets. This multiomics combined with high-throughput screening study reveals that SARS-CoV-2 not only modulates innate immunity, but also promotes viral infection, by hijacking ubiquitination-specific processes, highlighting potential antiviral and anti-inflammation targets.

SCI

English

First ; Corresponding

National key research and development program[2021YFC2300103] ; National Natural Science Foundation of China["82101857","82151212"] ; National Science Fund for Distinguished Young Scholars[82025022] ; Guangdong Provincial Department of Science and Technology[2021B1212030010] ; Shenzhen Science and Technology Innovation Committee[KQTD20200909113758004] ; Central Charity Fund of Chinese Academy of Medical Science[2020-PT310-009] ; Guangzhou Lab Emerging Funding[EKPG21-03]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000850803100001

SPRINGERNATURE

Web of Science

1.Southern Univ Sci & Technol, Natl Clin Res Ctr Infect Dis, Inst Hepatol, Shenzhen Peoples Hosp 3,Affiliated Hosp 2,Sch Med, Shenzhen 518112, Guangdong, Peoples R China
2.Guangzhou Med Univ, Guangzhou Lab, Guangzhou, Peoples R China
3.Second Mil Med Univ, Dept Microbiol, Shanghai Key Lab Med Biodef, Shanghai 200433, Peoples R China
4.Guangdong Key Lab Antiinfect Drug Qual Evaluat, Shenzhen 518112, Guangdong, Peoples R China
5.Chinese Acad Med Sci, Shenzhen Res Ctr Communicable Dis Diag & Treatmen, Shenzhen, Guangdong, Peoples R China

Xu, Gang,Wu, Yezi,Xiao, Tongyang,et al. Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2[J]. Signal Transduction and Targeted Therapy,2022,7(1).

Xu, Gang.,Wu, Yezi.,Xiao, Tongyang.,Qi, Furong.,Fan, Lujie.,...&Zhang, Zheng.(2022).Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2.Signal Transduction and Targeted Therapy,7(1).

Xu, Gang,et al."Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2".Signal Transduction and Targeted Therapy 7.1(2022).