J Bacteriol Virol.  2013 Sep;43(3):210-216. 10.4167/jbv.2013.43.3.210.

Cardiac-specific Coxsackievirus and Adenovirus Receptor (CAR) Deletion Inhibit Enterovirus Infection in Murine Heart

Affiliations
  • 1Department of Biomedical Science, Jungwon University, Goesan-gun, Chungbuk, Korea. bklim@jwu.ac.kr
  • 2Department of Herber Skin Care, College of Herbal Bio-industry, Gyeongsan-si, Gyeongsangbuk-do, Korea.

Abstract

The structure of coxsackievirus and adenovirus receptor's CAR is similar to adhesion molecules. In the adult heart, the majority of CAR localizes at the intercalated disc. Germ line CAR deletion induces embryonic lethality at E11.5 with evidence of a cardiac abnormality. The CAR role as a viral receptor is well known; however, its precise function in the heart for enterovirus infection is not clear. To understand the role of CAR in the cardiac myocyte, we generated cardiac-specific CAR knockout mice using a CAR floxed allele and alpha-MHC-Mer CRE Mer mice. Western blot analysis and immunofluorescent stain of ventricles at 6 weeks after 2 weeks tamoxifen administration, CAR expression was significantly decreased in CAR(f/f) MCM mice but not in CAR(f/f) mice heart. Enterovirus was intraperitoneally infected into CAR(f/f) MCM and CAR(f/f) mice (n=10 each). CAR disruption was dramatically reduced virus infection and replication in the heart but not different in liver, spleen, and pancreas. Cardiac myocyte damage was significantly reduced in the CAR(f/f) MCM mutant mice by evans blue dye stain. In addition, the CAR(f/f) MCM mutant mice heart inflammation and fibrosis were decreased in H&E and trichrome stain compare to CAR(f/f) control mice. CAR expression was required for normal ventricular function, but it is the cause of enterovirus infection. In the adult mice heart, CAR deletion was significantly reduced viral infection, proliferation, and myocarditis. These results suggested that CAR deletion could be useful therapeutic strategy to prevent viral myocarditis.

Keyword

Coxsackievirus and adenovirus receptor; Cardiomyocyte; Enterovirus; Inflammation; Myocaditis

MeSH Terms

Adenoviridae
Adult
Alleles
Animals
Azo Compounds
Blotting, Western
Enterovirus
Enterovirus Infections
Eosine Yellowish-(YS)
Evans Blue
Fibrosis
Germ Cells
Heart
Humans
Inflammation
Liver
Methyl Green
Mice
Mice, Knockout
Myocarditis
Myocytes, Cardiac
Pancreas
Receptors, Virus
Spleen
Tamoxifen
Ventricular Function
Viruses
Azo Compounds
Eosine Yellowish-(YS)
Evans Blue
Methyl Green
Receptors, Virus
Tamoxifen
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