BREAKING! COVID-19 Research: University Of Alabama Identify Fifteen Viral Genes Expressed In Human Lung Epithelial Cells Infected With SARS-CoV-2
: Leading molecular and cellular pathologists from the University of Alabama have now identified 15 main viral genes explicitly expressed in human lung epithelial cells infected by the SARS-CoV-2 coronavirus.
The research lead by Dr Sooryanarayana Varambally, Dr Darshan S. Chandrashekar and Dr Upender Manne, all from the Department of Pathology, University of Alabama at Birmingham could help reveal new therapeutic targets.
The study findings were published in a preprint server. https://www.biorxiv.org/content/10.1101/2020.06.24.169268v1
In order to understand more about how viruses like the various coronaviruses affect human host cells, high-throughput RNA sequencing, and microarray technologies help to detect and uncover the molecular changes following respiratory virus infections.
Bioinformatic analyses of the vast amount of data available plays a critical role in order to extract useful information and insights.
The research study by the scientists from the University of Alabama utilized the meta-analysis of such data to understand how SARS-CoV-2 affects the cell at the molecular level and how it is similar to and different from other respiratory viruses, and which parts of the virus-host cell interaction are susceptible to drug inhibition.
The study findings show that SARS-CoV-2 infected human bronchial epithelial cells show altered gene expression, some of which related to type I interferon signaling pathways and others to the inflammatory response, immune pathways, antiviral responses and other reactions to the presence of the virus.
By further meta-analyzing five studies on human lung epithelial cells infected by other viruses, they researchers found that this also showed differential expression of various genes following infection.
Subsequently these differentially expressed genes (DEGs) were then compared with those found in SARS-CoV-2 infection, to arrive at 15 genes that were differentially expressed specifically in the latter. Some of these were upregulated, while others were suppressed.
Association of COVID 19 hub genes with other respiratory viral infections. A network generated by use of
Cytoscape depicts the expression of COVID-19 hub genes on infection by various respiratory viruses.
The green arrows indicate down-regulation, and the red arrows show up-regulation of these genes.
Most significantly, among these are genes is the the colony-stimulating factor 2 (CSF2) that encodes a key cytokine elevated in many respiratory diseases such as pulmonary alveolar proteinosis.
Others identified include the S100 calcium-binding protein A9 (S100A9) and S100A8, which bind calcium and zinc and are found at high levels in lung inflammation.
Also found was the transcriptional and immune response regulator (TCIM) which is a positive regulator of cell proliferation pathways in thyroid cancer.
At the same time, the cysteine-rich C-terminal 1 (CRCT1) gene, found to act as a tumor suppressor was also identified among the 15 genes.
Another, the tripartite motif family-like 2 (TRIML2) gene enhances the growth of human mouth cancers.
Another similar gene found is the C-X-C Motif chemokine ligand 14 (CXCL14), which suppresses the growth of cancer cells in the mouth, lung, and the head and neck, besides prostate and breast cancers.
Other genes identified include Hephaestin-like 1 (HEPHL1), which is a glycoprotein that has ferroxidase activity, and MAS-related GPR family member X3 (MRGPRX3) that is part of the G-protein coupled receptor family. The latter is found to be reduced in expression in human bronchial epithelium after exposure to smoke from e-cigarettes.
Furthermore, the expression of the apoptosis pathway and type I interferon signaling pathway genes were also found to be commonly affected by both SARS-CoV-2 and other viral infections.
Though another analysis of over 1,000 interactions between almost 170 host cell and viral proteins shows that 24 genes may be considered as hub genes,among these, the only one that is exclusively expressed in cells infected by SARS-CoV-2 is the CSF2.
However in contrast, the others are almost always altered in cells infected by other respiratory viruses as well.
Most significantly, the CSF2 gene is therefore suspected of having a central role in facilitating SARS-CoV-2 infection of the human lung epithelial cells.
Dr Varambally told Thailand Medical News, “Both PPI analysis and comparative transcriptome analysis point to a role of CSF2 in the molecular mechanism of SARS-CoV-2 infections of human lung epithelium. The current study also highlights the exclusivity of known lung inflammation disorder genes such as S100A8 and S100A9 with respect to SARS-CoV-2 infection.”
He added, “These study findings will now need to be experimentally validated to find optimal molecular targets that can be used to develop therapies against the SARS-CoV-2 coronavirus.”
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