A Novel Murine Model of Parvovirus Associated Dilated Cardiomyopathy Induced by Immunization with VP1-Unique Region of Parvovirus B19

الملخص EN

Background.

Parvovirus B19 (B19V) is a common finding in endomyocardial biopsy specimens from myocarditis and dilated cardiomyopathy patients.

However, current understanding of how B19V is contributing to cardiac damage is rather limited due to the lack of appropriate mice models.

In this work we demonstrate that immunization of BALB/c mice with the major immunogenic determinant of B19V located in the unique sequence of capsid protein VP1 (VP1u) is an adequate model to study B19V associated heart damage.

Methods and Results.

We immunized mice in the experimental group with recombinant VP1u; immunization with cardiac myosin derived peptide served as a positive reference and phosphate buffered saline served as negative control.

Cardiac function and dimensions were followed echocardiographically 69 days after immunization.

Progressive dilatation of left ventricle and decline of ejection fraction were observed in VP1u- and myosin-immunized mice.

Histologically, severe cardiac fibrosis and accumulation of heart failure cells in lungs were observed 69 days after immunization.

Transcriptomic profiling revealed ongoing cardiac remodeling and immune process in VP1u- and myosin-immunized mice.

Conclusions.

Immunization of BALB/c mice with VP1u induces dilated cardiomyopathy in BALB/c mice and it could be used as a model to study clinically relevant B19V associated cardiac damage.