A Novel Murine Model of Parvovirus Associated Dilated Cardiomyopathy Induced by Immunization with VP1-Unique Region of Parvovirus B19.
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.
Department of Integrative Pathophysiology, Medical Faculty Mannheim, Mannheim, Germany; Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Julijus
0000-0001-8344-1909
J
Bogomolovas
Department of Biological Models, Institute of Biochemistry, Vilnius University, Vilnius, Lithuania.
Egidijus
E
Šimoliūnas
Department of Biological Models, Institute of Biochemistry, Vilnius University, Vilnius, Lithuania.
Ieva
I
Rinkūnaitė
Department of Integrative Pathophysiology, Medical Faculty Mannheim, Mannheim, Germany.
Luka
L
Smalinskaitė
Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Andrej
A
Podkopajev
State Research Institute, Centre for Innovative Medicine, Department of Stem Cell Biology, Vilnius, Lithuania.
Daiva
D
Bironaitė
Medical Faculty Mannheim, Institute of Pathology, Mannheim, Germany.
Cleo-Aron
CA
Weis
Medical Faculty Mannheim, Institute of Pathology, Mannheim, Germany.
Alexander
A
Marx
Department of Biological Models, Institute of Biochemistry, Vilnius University, Vilnius, Lithuania.
Virginija
V
Bukelskienė
Medical Faculty Mannheim, Medical Research Centre, Mannheim, Germany.
Norbert
N
Gretz
Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Virginija
V
Grabauskienė
Department of Integrative Pathophysiology, Medical Faculty Mannheim, Mannheim, Germany.
Dittmar
D
Labeit
Department of Integrative Pathophysiology, Medical Faculty Mannheim, Mannheim, Germany.
Siegfried
S
Labeit
D000818:Animals; D036022:Capsid Proteins / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000821:virology*; D004195:Disease Models, Animal; D004452:Echocardiography; D000939:Epitopes / Q000276:immunology; D020869:Gene Expression Profiling; D006524:Hepatitis, Viral, Animal / Q000276:immunology; D007114:Immunization; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016732:Parvovirus B19, Human / Q000235:genetics*; D010641:Phenotype; D059467:Transcriptome; D014612:Vaccines
D036022:Capsid Proteins; D000939:Epitopes; D018836:Inflammation Mediators; D014612:Vaccines; C095547:capsid protein VP1, parvovirus B19