SARS-CoV-2/human interactome reveals ACE2 locus crosstalk with the immune regulatory network in the host
| Autor: | Christy Lite, Melita Juliet, Allen J. Freddy, Shiek S. S. J. Ahmed |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Microbiology (medical) Angiotensins ACE2/AGT-axis Gene regulatory network Plasma protein binding Biology medicine.disease_cause immune response Immunomodulation 03 medical and health sciences 0302 clinical medicine Immune system medicine Humans Immunology and Allergy Gene Regulatory Networks Receptor 030304 developmental biology Coronavirus Regulation of gene expression AcademicSubjects/SCI01150 0303 health sciences General Immunology and Microbiology SARS-CoV-2 Gene Expression Profiling COVID-19 General Medicine Cell biology Crosstalk (biology) Infectious Diseases Gene Expression Regulation 030220 oncology & carcinogenesis Host-Pathogen Interactions Angiotensin-Converting Enzyme 2 Signal transduction AcademicSubjects/MED00690 Protein Binding Signal Transduction Research Article |
| Zdroj: | Pathogens and Disease |
| ISSN: | 2049-632X |
| Popis: | Severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), remains to be a threat across the globe. SARS-CoV-2 entry into the host is mediated by binding of viral spike protein to the Human angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is an essential member of the Renin–Angiotensin system (RAS) involved in maintaining the blood pressure and vascular remodelling. Although ACE2 receptor is the entry point to the host, recent studies show activation of ACE2 to modulate the host to develop a suitable environment for its replication. However, the ACE2 activating the immune signals on SARS-CoV-2 attachment is still under investigation. We have used systems biological approach to construct the host regulatory network upon SARS-CoV-2 attachment to the ACE2 receptor. Since lungs are the primary infection site, we integrate human lung gene expression profile along with the host regulatory network to demonstrate the altered host signalling mechanism in viral infection. Further, the network was functionally enriched to determine immune modulation in the network. We also used the proteomic database to assess the occurrence of similar signalling events in other human tissues that exhibit lineage of infection across different organs. The constructed network contains 133 host proteins with 298 interactions that directly or indirectly connect to the ACE2 receptor. Among 133 proteins, 29 were found to be differentially regulated in the host lungs on SARS-CoV-2 infection. Altered proteins connect multiple proteins in a network that modulates kinase, carboxypeptidase and cytokine activity, leading to changes in the host immune system, cell cycle and signal transduction mechanisms. Further investigation showed the presence of similar signalling events in the kidneys, placenta, pancreas, testis, small intestine and adrenal gland as well. Overall, our results will help in understanding the immune molecular regulatory networks influenced by the ACE2 mediated interaction in other body tissues, which may aid in identifying the secondary health complications associated with SARS-CoV-2 infection. The authors expect their results will help advance understanding of the immune molecular regulatory networks influenced by the ACE2 receptor-mediated interaction in other body tissues, which could help find the secondary health complications associated with SARS-CoV-2 infection. |
| Databáze: | OpenAIRE |
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