Transcriptome profiling of different types of human respiratory tract cells infected by SARS-CoV-2 highlight an unique role for inflammatory and interferon response

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) at the end of 2019 has caused a large global outbreak and now become a major public health issue. However, there is currently a lack of data underlying how the human host interacts with SARS-CoV-2 virus. In the current study, We performed Venn-analysis, Gene ontology (GO), KEGG pathway analysis and Protein-protein interaction analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during human respiratory tract cell infection with SARS-CoV-2. We found 36 overlapping upregulated genes among different types of cells after viral infection. Further functional enrichment analysis revealed these Differential Expressed Genes (DEGs) are most likely involved in biological processes related to inflammatory response and response to cytokine, cell component related to extracellular space and I-kappa B/NF-kappa B complex, molecular function related to protein binding and cytokine activity. KEGG pathways analysis highlighted altered conical and casual pathways related to TNF, NF-kappa B, Cytokine-cytokine receptor interaction and IL-17 signaling pathways during SARS CoV-2 infection with CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, IL32, CX3CL1, CCL20, IRF1, NFKB2 and NFKB1A up-regulated which may explain the inflammatory cytokine storms associated with severe cases of COVID-19.

KEYWORDS:

• SARS-CoV-2
• transcriptomics
• gene ontology
• pathway analysis
• inflammatory response

Acknowledgements

This work was supported by Shenzhen Natural Science Foundation (JCYJ20190809152415652), China Postdoctoral Science Foundation (2019M660836), the National Science and Technology Major Project (2018ZX10711001, 2017ZX10103011, 2018ZX09711003, and 2020YFC0841700), Shenzhen Science and Technology Research and Development Project (202002073000001). Yingxia Liu, Yu Wang, Minghui Yang and Luping Lei contributed to the study design. Minghui Yang, Luping Lei, Yang Yang and Jun Wang contributed to the manuscript and figures. Qiumei Cao, Xiao Jiang, Jinzhi Lai, Ling Qing and Kun Huang contributed to the proof reading. All the authors have read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

We searched for RNA-Seq experiments deposited in the Gene Expression Omnibus (GEO) database and NCBI PubMed related to SARS-CoV-2 infection in different types of human respiratory tract cells (Calu-3, doi:10.3390/biology9090260; ACE2-A549, GSE154613; a lung organoid model driving by human pluripotent stem cells, GSE155241; Primary human bronchial epithelial cells, GSE150819) which carried out in human cells (ex vivo) or human cell lines (in vitro).

Additional information

Funding

This work was supported by Shenzhen Natural Science Foundation [grant number JCYJ20190809152415652], China Postdoctoral Science Foundation [grant number 2019M660836], Shenzhen Key Technology Research Project [grant number JSGG20200207161928126], the National Science and Technology Major Project [grant numbers 2018ZX10711001, 2017ZX10103011, 2018ZX09711003, and 2020YFC0841700], and Shenzhen Science and Technology Research and Development Project [grant number 202002073000001].