Myocarditis in newborn wild-type BALB/c mice infected with the murine gamma herpesvirus MHV-68.
OBJECTIVE
Animal models of human Epstein-Barr virus (EBV) infection include EBV infection of primates and infection of mice with MHV-68, a further gamma herpesvirus (gamma-HV). We aimed at extending the MHV-68 model to study gamma-HV-related cardiac disease.


METHODS
Newborn wild-type BALB/c- (n=107), wild-type C57BL/6- (n=17) and immunodeficient B6-(Rag1) mice (n=18) were infected by nasal inoculation and evaluated for histopathological changes as well as tissue viral loads.


RESULTS
From day 5 on BALB/c mice showed myocardial viral replication. Whereas focal inflammation occurred simultaneously, necrosis was first observed 9 days post-infection. The maximum rates of necrosis (40%) and of focal inflammation (33%) were found after 10 to 12 and 33 to 35 days, respectively. Some animals developed persistent viral activity and inflammation throughout the observation period of three months. Inflammation was mainly related to T cell infiltrates. Although C57BL/6 mice also showed myocardial inflammation, necrosis was not found suggesting differences in the susceptibility to the virus in distinct mouse strains. In immunodeficient animals higher myocardial viral loads were observed compared to wild-type mice but no cardiac lesions, which suggests that the antiviral immune response contributed to the lesions.


CONCLUSIONS
The model system presented here is the first to allow detailed studies on cardiac disease caused by gamma-HV infections and may facilitate the development of more specific treatment options for human cardiac EBV infection.
Department of Pediatrics, University Hospital, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. Haeusler@rwth-aachen.de
Martin
M
Häusler
Bernd
B
Sellhaus
Simone
S
Scheithauer
Bärbel
B
Gaida
Sabrina
S
Kuropka
Katharina
K
Siepmann
Anna
A
Panek
Wibke
W
Berg
Andreas
A
Teubner
Klaus
K
Ritter
Michael
M
Kleines
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis; D004195:Disease Models, Animal; D006566:Herpesviridae Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000209:etiology* / Q000473:pathology / Q000821:virology; D009206:Myocardium / Q000473:pathology; D018144:Rhadinovirus / Q000276:immunology / Q000302:isolation & purification; D014412:Tumor Virus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology
D000956:Antigens, Viral; D001323:Autoantibodies