The University of Texas Medical Branch at Galveston
Research Project: Revealing HMGB1 Protein’s Role in COVID-19 Disease
COVID-19 Respiratory Virus Research Award
basic biologic mechanisms
The ongoing devastating COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in overwhelming number of deaths worldwide and still rising. New variants of the virus continue to emerge, such as the recent Delta, Omicron and now its subvariants, which have crippled the world’s economy and weakened healthcare systems. SARS-CoV-2 infection induces an unwanted inflammatory response that can lead to lethal outcomes of COVID-19 disease. We have identified a protein called high mobility group box 1 (HMGB1), which alerts the immune system of potential damage that can be inflicted during SARS-CoV-2 infection. We will investigate the role of HMGB1 in SARS-CoV-2 infection, which may guide us on the development of novel therapeutic strategies to mitigate the COVID-19 pandemic.
Our studies demonstrated both the beneficial and the detrimental role of high mobility group box-1 (HMGB1) in promoting inflammation during SARS-CoV-2 infection. Our findings suggest that initial low levels of HMGB1 secretion are essential in alerting the immune system to tissue damage. However, excessive HMGB1 secretion promotes massive production of proinflammatory mediators called cytokines in immune cells, leading to uncontrolled inflammation and an impaired immune system. These findings suggest that modulation of HMGB1’s pro-inflammatory function could prevent acute and damaging inflammatory responses not only in COVID-19 patients but also for other emerging respiratory viral infections that affect the human population of all age groups.