Coxsackievirus B3 Induces Autophagic Response in Cardiac Myocytes in vivo

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Xia Zhai^1#, Bing Bai^2#, Bohai Yu¹, Tanying Wang¹, Huapeng Wang³, Yao Wang³, Huiyan Li², Lei Tong¹, Yan Wang¹, Fengmin Zhang¹, Wenran Zhao^3*, and Zhaohua Zhong^1*

¹Department of Microbiology, Harbin Medical University, 194 Xuefu Road, Harbin 150086, China; E-mail: zhonghzh@hrbmu.edu.cn

²Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, China

³Department of Cell Biology, Harbin Medical University, 194 Xuefu Road, Harbin 150086, China; E-mail: zhaowr@ems.hrbmu.edu.cn; zhaowenran2002@aliyun.com

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received November 20, 2014; Revision received February 9, 2015

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Viral myocarditis is a common disease that contributes to dilated cardiomyopathy or heart failure. Coxsackievirus B (CVB) is one of the major causative pathogens of viral myocarditis. Previous studies have shown that autophagy is exploited to promote CVB replication in cell lines. To study whether cardiac myocytes respond to CVB infection in a similar way, viral myocarditis was established by the inoculation of 3-week-old BALB/c mice with CVB3. Electron microscopic observation showed that autophagosome-like vesicles were induced in the cardiac myocytes of mice infected by CVB3 at 3, 5, and 7 days after viral infection. The lipidated microtubule-associated protein 1 light chain 3 (LC3), LC3-II, was also significantly increased in both myocardium and the cardiac myocytes extracted from the ventricles of mice infected with CVB3. The increased LC3-II coincided with high level of viral RNA and proteins in both myocardium and isolated cardiac myocytes. Moreover, viral protein synthesis was significantly decreased in primary cardiac myocytes by the treatment with 3-methyladenine, an inhibitor of autophagy. The expression and the phosphorylation of extracellular signal regulated kinase (ERK) were also increased in both myocardium and in the isolated cardiac myocytes of the virus-infected mice, while the interplay of ERK with autophagic response remains to be studied. This study demonstrated that cardiac myocytes respond to CVB3 infection by increased formation of autophagosomes in vivo, which might be exploited for viral replication.

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KEY WORDS: coxsackievirus B, cardiac myocytes, myocardium, autophagy, autophagosome

DOI: 10.1134/S0006297915080052

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