Abstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we collected open access data to analyze the mechanisms associated with SARS-CoV-2 infection. Gene set enrichment analysis (GSEA) revealed that apoptosis-related pathways were enriched in the cells after SARS-CoV-2 infection, and the results of differential expression analysis showed that biological functions related to endoplasmic reticulum stress (ERS) and lipid metabolism were disordered. TMBIM6 was identified as a potential target for SARS-CoV-2 in host cells through weighted gene coexpression network analysis (WGCNA) of the time course of expression of host and viral proteins. The expression and related functions of TMBIM6 were subsequently analyzed to illuminate how viral proteins interfere with the physiological function of host cells. The potential function of viral proteins was further analyzed by GEne Network Inference with Ensemble of trees (GENIE3). This study identified TMBIM6 as a target protein associated with the pathogenesis of SARS-CoV-2, which might provide a novel therapeutic approach for COVID-19 in the future.
Highlights
The outbreak of SARS-CoV-2 has disseminated to 216 countries and regions around the world [1]
We obtained transcriptome data of Caco-2 cells infected with SARS-CoV-2 at different time points from Emanuel et al, which consists of 45058 genes with quantifications in Caco-2 cells [11]
The proteome data from cells infected with SARS-CoV-2 [13], influenza A virus (IAV) [14] and respiratory syncytial virus (RSV) [15], which provided the information of differentially expressed proteins, were collected as a source of circumstantial evidence
Summary
The outbreak of SARS-CoV-2 has disseminated to 216 countries and regions around the world [1]. Similar to SARSCoV [6, 7], the spike protein of SARS-CoV-2 directly interacts with the receptor ACE2 on the membrane of human airway epithelial cells to promote virus invasion [8, 9]. Many studies have focused on the receptors for the spike protein of SARS-CoV-2, especially ACE2; the intracellular mechanism used by the virus to achieve amplification and regulate the protein expression of host cells is largely unknown. Gene set enrichment analysis (GSEA) with proteome data was performed to analyze the enriched signaling pathways of differentially expressed proteins induced by SARS-CoV-2 virus invasion. Through integrated bioinformatic analysis of transcriptome, translatome and proteome data, we found that the TMBIM6 protein in host cells was inhibited by SARSCoV-2 at the posttranscriptional level to mediate the host cell response to virus infection
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