PhIP-Seq analysis reveals autoantibodies for novel antigens in the mouse model of Coxsackievirus B3 infection

Abstract Myocarditis is a frequent occurrence in children and adolescents that can lead to dilated cardiomyopathy, and viruses are commonly suspected in those affected. Experimentally, Coxsackievirus B3 (CVB) infection in mice occurs in viral and non-viral phases, but in continuum, and histologically, the disease features have similarities with that of human disease. Mechanistically, by using traditional methods, autoantibodies have been demonstrated for various antigens in post-infectious myocarditis leading to a suggestion that autoimmunity could be an underlying mechanism. However, their role continues to be enigmatic, raising a question that whether autoantibody repertoires are sufficiently characterized. Here, we describe a versatile and high-throughput, phage-immunoprecipitation sequencing platform that permitted us to comprehensively evaluate antibody reactivities in serum samples harvested from mice infected with CVB. By screening the phage-displayed virus library (VirScan), antibody reactivity occurred specifically to CVB, and thus, validating our methodology. Similar analysis with the human library revealed antibody reactivity for antigens conserved in both humans and mice, suggesting a role for them in the viral pathogenesis. Alternatively, detection of these autoantibodies may have a diagnostic value in the evaluation of myocardial damage, including cardiac autoimmunity as might occur in CVB infection.