J Vet Sci.  2017 Dec;18(4):457-464. 10.4142/jvs.2017.18.4.457.

Pathogenesis of coxsackievirus B2 in mice: characterization of clinical isolates of the coxsackievirus B2 from patients with myocarditis and aseptic meningitis in Korea

• Hong J
• Kang B
• Yeo S
• Jee Y
• Park JH

• KMID: 2398504
• DOI: http://doi.org/10.4142/jvs.2017.18.4.457

Abstract

Group B coxsackieviruses (CVBs) are a group of common human pathogens producing various clinical symptoms. Although the virology of CVB is well known, there is limited information on viral pathogenesis and the relationship between clinical symptoms and viral phenotype, particularly for CVB type 2 (CVB2). In 2004 in Korea, two CVB2 strains were isolated: CB2/04/279 from stool of an acute myocarditis patient with heart failure and CB2/04/243 from an aseptic meningitis patient. In this study, a high degree of homology was observed between the CB2/04/279 and CB2/04/243 full genome sequences. The two Korean CVB2 isolates had 93.1% homology compared to 82.1%-82.5% nucleotide sequence identity with the cardiovirulence-associated reference CVB strain Ohio-1 (CVB/O). CVB2-induced pathogenesis was analyzed, focusing on virus-induced pathology of various tissues in 4-week-old BALB/c inbred male mice. Myocarditis developed and extensive pancreatic inflammation was observed in all mice infected with CB2/04/279 or CVB/O, but not in animals infected with CB2/04/243. This is the first report of the full-genomic sequence and pathogenesis of the CVB2 strain isolated from an acute myocarditis patient in Korea.

Keyword

cardiovirulence; coxsackievirus B2; myocarditis; pathogenesis

MeSH Terms

Animals
Base Sequence
Enterovirus
Genome
Heart Failure
Humans
Inflammation
Korea*
Male
Meningitis, Aseptic*
Mice*
Myocarditis*
Pathology
Phenotype
Virology

Figure

• 

  Fig. 1 Histopathological lesions of the pancreas from mice inoculated with CVB2 on days 7 (A, C, E, and G) and 13 (B, D, F, and H) post-inoculation (pi). Mice were mock-infected with saline (A and B), or inoculated with CB2/04/243 (C and D), CB2/04/279 (E and F), or CVB/O (G and H). Mice were sacrificed on days 7 and 13 pi and pancreatic tissues were fixed in formalin, paraffin embedded, cross-sectioned at a 3 µm thickness, and stained with hematoxylin and eosin. 200×.

• 

  Fig. 2 Mice inoculated with CB2/04/243() were compared with those inoculated with CVB/O (■) and CB2/04/279 (□) for pancreatitis severity level on days 7 and 13 post-inoculation (pi). Average severity grades of lesions in animals: 1, minimal; 2, mild; 3, moderate; 4, marked. Severity grades among strains were compared by independent t-tests (n = 6 or 8 per group). *p < 0.05 considered statistically significant.

• 

  Fig. 3 Histopathological lesions of the hearts from mice inoculated with CVB2 on days 7 (A, C, E, and G) and 13 (B, D, F, and H) post-inoculation (pi). Mice were mock-infected with saline (A and B), or inoculated with CB2/04/243 (C and D), CB2/04/279 (E and F), or CVB/O (G and H). Mice were euthanized 7 and 13 days pi. Arrows indicate area of inflammation in heart. Hearts were fixed in formalin, paraffin embedded, cross-sectioned at a 3 µm thickness, and stained with hematoxylin and eosin. 100×.

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