Regulation of autophagy and inflammasome signaling by HMGB1-mediated inflammation during SARS-CoV-2 infection
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B650
Abstract ID: 5309
Presenting Author:
Yashoda M Hosakote , Assistant Professor at Univ. of Texas Med. Br., Galveston
Abstract:
The recent devastating COVID-19 pandemic caused by SARS-CoV-2 has resulted in >6.98 million deaths worldwide. Although the pathogenic mechanisms of SARS-CoV-2 infection are still unclear, disease severity in patients is linked not only to replication of the virus but also to the host inflammatory response. Therefore, controlling the host inflammatory response is likely as important as targeting the virus. The high mobility group box 1 protein (HMGB1) is an endogenous danger molecule that is released to signal tissue damage. HMGB1 has been shown to function in regulation of cellular transcription and activation of proinflammatory responses in many pathogenic conditions, but little is known about its role in SARS-CoV-2-induced lung inflammation. In this study, we infected lung epithelial cells and mice with SARS-CoV-2 to investigate the mechanism of HMGB1 release in regulating immune signaling to induce inflammation. We found that SARS-CoV-2 induces autophagy and pyroptosis, and downregulates inflammasome activation in lung epithelial cells, leading to increased virus replication. Treatment of SARS-CoV-2-infected lung epithelial cells with recombinant HMGB1 inhibited autophagy and pyroptosis via the activation of inflammasomes, and inhibited virus replication. These findings suggest that SARS-CoV-2-induced HMGB1 release mediates the activation of innate immune response to promote inflammation and could represent a novel therapeutic strategy to decrease the severity of COVID-19.
Regulation of autophagy and inflammasome signaling by HMGB1-mediated inflammation during SARS-CoV-2 infection
Category
Poster