Desmin mutations in cardiomyocytes increase susceptibility to coxsackievirus B3 infection by impairing antiviral IFN-β response and upregulating viral receptors expression.

backgroundDesmin-related cardiomyopathies caused by mutations in the DES gene are characterized by cytoskeletal disorganization and impaired cardiomyocyte function. Viral infections, particularly with Coxsackievirus B3 (CVB3), have been implicated as environmental triggers for cardiac decompensation. However, the interaction between desmin mutations and viral infection has never been explored.

methodsHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a healthy donor (control-CMs) and from patients carrying DES

resultsDES

conclusionCVB3/28 infection compromises the structural integrity and contractile function of cardiomyocytes and exerts a more severe effect in cells harboring DES mutations. These findings underscore a pathogenic synergy between genetic cytoskeletal defects and viral infection, revealing a mechanistic basis for the heightened vulnerability of patients carrying mutation in DES gene to virus-induced cardiac decompensation. CVB3/28 infection disrupts cardiomyocyte structure and impairs contractility, with more severe effects in cells carrying DES mutations. By enhancing viral replication and weakening antiviral defenses, DES mutations act synergistically with CVB3/28 infection to increase the risk of cardiac dysfunction.