Integrated interactome and transcriptome analysis reveals key host factors critical for SARS-CoV-2 infection

Jie Sheng; Lili Li; Xueying Lv; Meiling Gao; Ziyi Chen; Zhuo Zhou; Jingfeng Wang; Aiping Wu; Taijiao Jiang

doi:10.1016/j.virs.2023.05.004

August 2023

Citation: Jie Sheng, Lili Li, Xueying Lv, Meiling Gao, Ziyi Chen, Zhuo Zhou, Jingfeng Wang, Aiping Wu, Taijiao Jiang. Integrated interactome and transcriptome analysis reveals key host factors critical for SARS-CoV-2 infection .VIROLOGICA SINICA, 2023, 38(4) : 508-519. http://dx.doi.org/10.1016/j.virs.2023.05.004

Integrated interactome and transcriptome analysis reveals key host factors critical for SARS-CoV-2 infection

Jie Sheng ^a,b,c ,
Lili Li ^a,b ,
Xueying Lv ^a,b,d ,
Meiling Gao ^a,b ,
Ziyi Chen ^a,b ,
Zhuo Zhou ^a,b ,
Jingfeng Wang ^{a,b
,,} ,
Aiping Wu ^{a,b
,,} ,
Taijiao Jiang ^{a,b,e,f
,,}

a. Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China;
b. Suzhou Institute of Systems Medicine, Suzhou, 215123, China;
c. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China;
d. Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, China;
e. Guangzhou Laboratory, Guangzhou, 510005, China;
f. State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China

Corresponding author: Jingfeng Wang, wangjf@ism.cams.cn
Aiping Wu, wap@ism.cams.cn
Taijiao Jiang, jiang_taijiao@gzlab.ac.cn
Received Date: 16 January 2023
Accepted Date: 05 May 2023
Available online: 09 May 2023

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has seriously threatened global public health and caused huge economic losses. Omics studies of SARS-CoV-2 can help understand the interaction between the virus and host, thereby providing a new perspective in guiding the intervention and treatment of the SARS-CoV-2 infection. Since large amount of SARS-CoV-2 omics data have been accumulated in public databases, this study aimed to identify key host factors involved in SARS-CoV-2 infection through systematic integration of transcriptome and interactome data. By manually curating published studies, we obtained a comprehensive SARS-CoV-2-human protein-protein interactions (PPIs) network, comprising 3591 human proteins interacting with 31 SARS-CoV-2 viral proteins. Using the RobustRankAggregation method, we identified 123 multiple cell line common genes (CLCGs), of which 115 up-regulated CLCGs showed host enhanced innate immunity and chemotactic response signatures. Combined with network analysis, co-expression and functional enrichment analysis, we discovered four key host factors involved in SARS-CoV-2 infection: IFITM1, SERPINE1, DDX60, and TNFAIP2. Furthermore, SERPINE1 was found to facilitate SARS-CoV-2 replication, and can alleviate the endoplasmic reticulum (ER) stress induced by ORF8 protein through interaction with ORF8. Our findings highlight the importance of systematic integration analysis in understanding SARS-CoV-2-human interactions and provide valuable insights for future research on potential therapeutic targets against SARS-CoV-2 infection.
- SARS-CoV-2
- , Interactome
- , Transcriptome
- , Integration analysis
- , ER stress

Electronic Supplementary Material

10.1016j.virs.2023.05.004-ESM2.docx

10.1016j.virs.2023.05.004-ESM1.xlsx
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