Mount Sinai researchers discover novel receptors for SARS-CoV-2 and their age-dependent expression, providing new insights for public health

New York, NY (April 11, 2023) – A study led by Mount Sinai researchers Dr. Bin Zhang, the Willard T.C. Johnson Research Professor of Neurogenetics, and Dr. Christian Forst, an Associate Professor in the Department of Genetics and Genomic Sciences, have identified potential novel receptors for SARS-CoV-2 and unveiled their tissue-specific and age-dependent expression. The findings were published on March 23 in the Federation of European Biochemical Societies Letters.

The study's multiscale network analysis suggests that SARS-CoV-2 utilizes multiple novel receptors, such as the TYOBP receptor CD300e, to facilitate its life cycle and trigger a unique response in the host system. This receptor activates IL-2 pro-inflammatory cytokine signaling, which is believed to contribute to the severity of COVID-19. Researchers identified a strong correlation between tissue age-dependency and SARS-CoV-2 infection-induced receptor expression in subcutaneous fat, tibial artery, brain substantia nigra, esophagus gastroesophageal junction, and liver.

These findings reveal that SARS-CoV-2 may exploit different receptors and pathways across various tissues and age groups, with older adults being more susceptible to severe outcomes. The study's results also provide valuable information about the host response to the virus, the hijacking of key cellular processes, and the age-dependence of these receptors in different tissues.
 
“These findings provide crucial insights into the gene regulatory organization during SARS-CoV-2 infection and the tissue-specific, age-dependent expression of cell receptors involved in COVID-19,” said Dr. Bin Zhang. “This information is critical for public health as it allows us to better understand the molecular mechanisms of SARS-CoV-2 infection and develop new therapeutic interventions against COVID-19."
 
The study highlights the importance of understanding the host response to viral infections and how age can impact the severity of the disease. With these new insights, researchers can develop targeted therapies and interventions to mitigate the impacts of COVID-19 on vulnerable populations, such as older adults and individuals with pre-existing conditions.

The methods employed in this study involved a multiscale network analysis utilizing bulk and single-cell omics data, which allowed the researchers to analyze the complex biological systems of SARS-CoV-2 infection. They integrated large-scale transcriptomic datasets from COVID-19 patients and healthy individuals, along with protein-protein interaction (PPI) data and protein expression data, to construct a comprehensive host-virus interactome. This approach enabled them to identify key genes, proteins, and molecular pathways involved in SARS-CoV-2 infection and the host response, and the age-dependent expression patterns of novel receptors. The research team also validated the findings using a combination of in vitro and in vivo experiments, further substantiating the potential roles of the newly discovered receptors in SARS-CoV-2 infection and COVID-19 severity.

Dr. Christian Forst added, "The discovery of novel receptors that SARS-CoV-2 utilizes, and their age-dependent expression offers new avenues for research and potential therapeutic strategies. This could be especially significant for older adults who have a higher risk of severe COVID-19 outcomes. Our research will help guide public health strategies and support targeted therapies for vulnerable populations."

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The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population. Ranked 14th nationwide in National Institutes of Health (NIH) funding and among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators and clinicians work within and across 34 academic departments and 35 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases. Icahn Mount Sinai offers highly competitive MD, PhD, and Master’s degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System. To learn more, please visit https://icahn.mssm.edu/.