摘要
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 SARSCoV-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 SARSCoV-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.
基金
supported by the National Natural Science Foundation of China (32070678,82102371 and 31671371)
the Emergency Key Program of Guangzhou Laboratory,grant no.EKPG21-12
the Selfsupporting Program of Guangzhou Laboratory,Grant No.SRPG22-007,SRPG22-020
the National Key Research and Development Program of China (2020YFC0840800)
CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061)
the National Key Research and Development Program of China (2021YFC2302000).
