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β-arrestins (βarrs), initially discovered as desensitizers of GPCR signaling, are now known to function as intracellular scaffolds and signaling transducers mediating a wide array of signaling cascades including immune responses to inflammatory stimuli. An important cause of immune cell infiltration and cardiac inflammation are viral pathogens such as enterovirus coxsackievirus B3 (CVB3) induced myocarditis. While viral myocarditis is a leading cause of dilated cardiomyopathy, the precise molecular mechanisms for the acute immune response to CVB3 infection are not well understood. Given the important role for βarrs in the acute immune response, we tested the hypothesis that βarrs are necessary for the activation of the acute immune response and mediate the progression and severity of cardiotropic CVB3-induced myocarditis in mice. Five to 7-week-old mice devoid of βarr1 (βarr1 KO) or βarr2 (βarr2 KO) were …