Fri. Jan 21st, 2022

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a positive-stranded RNA virus that appears spherical under a transmission electron microscope. Many studies have shown that SARS-CoV-2 infects host cells through the interaction between the viral nail protein and the host receptor, angiotensin-converting enzyme II (ACE2). SARS-CoV-2 can be spread through saliva, airways, close contact and excrement with great potential for aerosol transfer.

Study: Identification of key pathways and genes in SARS-CoV-2 infection of human intestines by bioinformatics analysis.  Image credit: Limbitech / ShutterstockStudy: Identification of key pathways and genes in SARS-CoV-2 infection of human intestines by bioinformatics analysis. Image credit: Limbitech / Shutterstock

The most common clinical symptoms of (coronavirus disease 2019) COVID-19 are fever, cough and difficulty breathing, with some patients experiencing gastrointestinal upset, including nausea and vomiting. Studies have reported the presence of SARS-CoV-2 in the feces of COVID-19 patients, indicating the ability of the virus to infect the digestive tract.

Given that the effect of SARS-CoV-2 on the human digestive tract is a poorly studied topic, researchers from China recently used bioinformatics analysis techniques to explore the diseases caused by SARS-CoV-2 infection in the human digestive tract. This article is available in Biochem Genet.

The study

The researchers used bioinformatics analysis to identify and investigate the differential expression of microorganisms under different conditions and also used genontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to determine the biological significance of DEGs. The STRING database was used to establish a visual protein-protein interaction network (PPI) and Cytoscape to visualize PPI and outline the top 12 hub genes of the node.

The GSE149312 gene expression profile dataset was obtained from the Gene Expression Omnibus (GEO) database and was divided into a 24 hour and a 60 hour group. R-software was used for analysis and screening of differentially expressed genes (DEGs). The authors took the SARS-COV-2 infection group and the empty group from the original study and grouped them according to the time of infection. Each group had four infected samples and six control samples.

What did they find?

The biological process analysis showed that the DEGs in the 24-hour group were significantly enriched in nuclear division, mitotic nuclear division, mitotic sister chromatid segregation, negative cell cycle regulation, and chromosome separation. The DEGs for the 60 hour group were found in fatty acids and small molecule catabolic processes. They were significantly enriched in acid metabolic processes, cellular response to xenobiotic stimulus, long-chain fatty acid metabolic processes, and unsaturated fatty acid metabolic processes. Among them, no intersection was found between the 24-hour and 60-hour groups.

The KEGG assay results illustrated that the DEGs in the 24-hour group were significantly enriched in small cell lung cancer, cell cycle, cellular senescence, DNA replication, and non-alcoholic fatty liver disease. In contrast, the DEGs for the 60-hour group were found in mineral absorption and chemical carcinogenesis and were significantly enriched in drug metabolism, non-alcoholic fatty liver disease, and metabolism of xenobiotics by cytochrome P450. Among them, the non-alcoholic fatty liver disease pathway was co-expressed in both the 24-hour and 60-hour groups.

Using the STRING database, the team constructed PPI networks of the DEGs in both the 20- and 60-hour groups and the intersection group. The 24-hour PPI network had 1778 nodes and 1457 edges, the 60-hour group had included 710 nodes and 1457 edges, while the intersection group had 692 nodes and 162 edges.

Ni hub-gen

The results identified nine statistically significant hub genes – AKT1, TIMP1, NOTCH, CCNA2, RRM2, TTK, BUB1B, KIF20A and PLK1. They were uploaded to GraphPad Prism (version 8.0.2) in descending order and then analyzed using bioinformatics.

The ATK1 and TIMP1 genes show some stimulating effect on immune cells, including macrophages, and trigger the immune responses, indicating that SARS-CoV-2 can cause severe inflammatory bowel disease, diarrhea, fever and other symptoms after infection and eventually lead to damage to the gastrointestinal tract.

The TTK, BUB1B, PLK1 and CCNA2 genes play significant roles in the normal cell division cycle. The upregulation of these four genes during SARS-CoV-2 infection not only provides favorable conditions for viral transmission, but also highlights the possibility of chromosomal aberrations and other genetic damage in the host cells.

Conclusions

The study identifies the DEGs between SARS-CoV-2 and the normal samples. The nine hub genes obtained in this experiment play important roles in cell growth, reproduction, and disease. The work analyzed the differential expression of these genes during SARS-CoV-2 infection to understand the diseases that the virus can cause and enable timely prevention of them. However, this study is limited by its sample size and the fact that the intestinal organs could not accurately simulate the human environment.

In conclusion, the results of this study provide some direction and basis for follow-up studies of SARS-CoV-2 infection in the human digestive tract, while providing new insights into the prevention and treatment of diseases associated with SARS-CoV-2 infection.

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