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

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

  • Virol Sin. 2023 Aug;38(4):508-519. doi: 10.1016/j.virs.2023.05.004.
Jie Sheng 1,  Lili Li 2,  Xueying Lv 3,  Meiling Gao 2,  Ziyi Chen 2,  Zhuo Zhou 2,  Jingfeng Wang 4,  Aiping Wu 5,  Taijiao Jiang 6
Affiliations

Affiliations

  • 1 Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, China; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
  • 2 Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
  • 3 Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, China; Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, China.
  • 4 Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, China. Electronic address: [email protected].
  • 5 Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, China. Electronic address: [email protected].
  • 6 Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, 215123, China; Guangzhou Laboratory, Guangzhou, 510005, China; State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China. Electronic address: [email protected].
PMID: 37169126 DOI: 10.1016/j.virs.2023.05.004
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.

Keywords

ER stress; Integration analysis; Interactome; SARS-CoV-2; Transcriptome.

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