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Neutrophils, Crucial, or Harmful Immune Cells Involved in Coronavirus Infection: A Bioinformatics Study
Nima Hemmat1,2, Afshin Derakhshani1, Hossein Bannazadeh Baghi1,2
1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Insights
This study identifies key genes and biological processes involved in SARS-CoV infection, suggesting potential therapeutic targets like Serpins and Arginase inhibitors for both SARS and COVID-19 patients.
Area of Science:
- Virology
- Immunology
- Genomics
Background:
- Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and SARS-CoV-2 cause severe respiratory illnesses, including COVID-19, a global pandemic.
- The molecular mechanisms underlying SARS-CoV infection and its impact on the respiratory tract remain incompletely understood.
- Understanding the host response to SARS-CoV infection is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate the molecular mechanisms and host response in SARS-CoV infection.
- To identify key genes and biological pathways significantly altered during SARS-CoV infection.
- To explore potential therapeutic strategies for SARS-CoV and SARS-CoV-2 based on molecular findings.
Main Methods:
- Analysis of the GSE1739 microarray dataset comparing SARS-CoV-positive and normal peripheral blood mononuclear cells (PBMC).
- Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene modules associated with SARS-CoV infection.
- GEO2R analysis to pinpoint significant genes and Gene Ontology (GO) analysis to determine activated biological processes.
Main Results:
- A highly preserved 833-gene turquoise module was significantly related to SARS-CoV infection.
- Key genes identified include ELANE, ORM2, RETN, BPI, ARG1, DEFA4, CXCL1, and CAMP.
- GO analysis revealed neutrophil activation and degranulation as primary biological processes, with predicted neutrophilia, basophilia, and lymphopenia.
Conclusions:
- Neutrophil-related pathways are critically involved in the host response to SARS-CoV infection.
- Serpins and Arginase inhibitors may offer therapeutic benefits for patients with SARS-CoV infection.
- Given the similarity between SARS-CoV and SARS-CoV-2, these inhibitors could potentially benefit COVID-19 patients.
Abstract:
The latest member of the Coronaviridae family, called SARS-CoV-2, causes the Coronavirus Disease 2019 (COVID-19). The disease has caused a pandemic and is threatening global health. Similar to SARS-CoV, this new virus can potentially infect lower respiratory tract cells and can go on to cause severe acute respiratory tract syndrome, followed by pneumonia and even death in many nations. The molecular mechanism of the disease has not yet been evaluated until now. We analyzed the GSE1739 microarray dataset including 10 SARS-positive PBMC and four normal PBMC. Co-expression network analysis by WGCNA suggested that highly preserved 833 turquoise module with genes were significantly related to SARS-CoV infection. ELANE, ORM2, RETN, BPI, ARG1, DEFA4, CXCL1, and CAMP were the most important genes involved in this disease according to GEO2R analysis as well. The GO analysis demonstrated that neutrophil activation and neutrophil degranulation are the most activated biological processes in the SARS infection as well as the neutrophilia, basophilia, and lymphopenia predicted by deconvolution analysis of samples. Thus, using Serpins and Arginase inhibitors during SARS-CoV infection may be beneficial for increasing the survival of SARS-positive patients. Regarding the high similarity of SARS-CoV-2 to SARS-CoV, the use of such inhibitors might be beneficial for COVID-19 patients.
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