Int J Med Sci 2021; 18(5):1143-1152. doi:10.7150/ijms.52256

Research Paper

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection induces dysregulation of immunity: in silico gene expression analysis

Yen-Hung Wu1,2, I-Jeng Yeh1,2, Nam Nhut Phan3, Meng-Chi Yen1,2, Hsin-Liang Liu1, Chih-Yang Wang4,5✉, Hui-Ping Hsu6,7✉

1. Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
2. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
3. NTT Institute of Hi-Technology, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Vietnam.
4. PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
5. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
6. Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
7. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

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Citation:
Wu YH, Yeh IJ, Phan NN, Yen MC, Liu HL, Wang CY, Hsu HP. Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection induces dysregulation of immunity: in silico gene expression analysis. Int J Med Sci 2021; 18(5):1143-1152. doi:10.7150/ijms.52256. Available from https://www.medsci.org/v18p1143.htm

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Abstract

Highly pathogenic coronaviruses (CoVs) induce acute respiratory distress syndrome, and the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused a pandemic since late 2019. The diversity of clinical manifestations after SARS-CoV-2 infection results in great challenges to diagnose CoV disease 2019 (COVID-19). There is a growing body of published research on this topic; however, effective medications are still undergoing a long process of being assessed. In the search for potential genetic targets for this infection, we applied a holistic bioinformatics approach to study alterations of gene signatures between SARS-CoV-2-infected cells and mock-infected controls. Two different kinds of lung epithelial cells, A549 with angiotensin-converting enzyme 2 (ACE2) overexpression and normal human bronchial epithelial (NHBE) cells, were infected with SARS-CoV-2. We performed bioinformatics analyses of RNA-sequencing in this study. Through a Venn diagram, Database for Annotation, Visualization and Integrated Discovery, Gene Ontology, Ingenuity Pathway Analysis, and Gene Set Enrichment Analysis, the pathways and networks were constructed from commonly upregulated genes in SARS-CoV-2-infected lung epithelial cells. Genes associated with immune-related pathways, responses of host cells after intracellular infection, steroid hormone biosynthesis, receptor signaling, and the complement system were enriched. Dysregulation of the immune system and malfunction of interferon contribute to a failure to kill SARS-CoV-2 and exacerbate respiratory distress in severely ill patients. Current findings from this study provide a comprehensive investigation of SARS-CoV-2 infection using high-throughput technology.

Keywords: coronavirus, SARS-CoV-2, COVID-19, interferon, immune system