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Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
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CARD8 makes coxsackievirus more "heartbreaking"
Qiankun Wang1, Liang Shan1,2
1Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
The Journal of Experimental Medicine
|September 21, 2022
Insights
Researchers found that CARD8 acts as an innate sensor. It is triggered by coxsackievirus B3 proteases, causing cell death and promoting heart inflammation and viral replication.
Area of Science:
- Immunology
- Virology
- Cardiovascular Science
Background:
- Coxsackievirus B3 (CVB3) is a significant cause of viral myocarditis.
- The mechanisms by which CVB3 induces heart inflammation and cell damage are not fully understood.
- Innate immune sensors play a crucial role in antiviral responses.
Purpose of the Study:
- To identify innate immune sensors involved in the response to CVB3 infection.
- To elucidate the role of these sensors in pyroptosis of cardiac and endothelial cells.
- To understand how this process contributes to viral myocarditis.
Main Methods:
- Utilized cell culture models of aortic endothelial cells and cardiac myocytes.
- Employed coxsackievirus B3 infection models.
- Investigated the activation of CARD8 inflammasome and its role in pyroptosis.
- Assessed viral replication and inflammatory markers.
Main Results:
- Identified CARD8 as a key innate sensor activated by CVB3 proteases.
- Demonstrated that CVB3 protease activity triggers CARD8-dependent pyroptosis in aortic endothelial cells and cardiac myocytes.
- Showed that pyroptosis fueled viral replication and promoted inflammation in the heart.
- Established a link between CARD8 activation and the pathogenesis of CVB3-induced myocarditis.
Conclusions:
- CARD8 serves as an innate sensor that detects CVB3 infection.
- CVB3-induced pyroptosis mediated by CARD8 contributes to viral replication and myocarditis.
- Targeting CARD8-mediated pyroptosis may offer a therapeutic strategy for viral heart disease.
Abstract:
In this issue of JEM, Nadkarni et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20212117) identify CARD8 as an innate sensor triggered by coxsackievirus B3 proteases to drive pyroptosis of aortic endothelial cells and cardiac myocytes, fueling viral replication and heart inflammation.
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