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Journal of Virology, November 2004, p. 12548-12556, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12548-12556.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Coxsackievirus Group B Type 3 Infection Upregulates Expression of Monocyte Chemoattractant Protein 1 in Cardiac Myocytes, Which Leads to Enhanced Migration of Mononuclear Cells in Viral Myocarditis

Yan Shen,{dagger} Wei Xu, Yi-Wei Chu, Ying Wang, Quan-Sheng Liu, and Si-Dong Xiong*

Department of Immunology, Shanghai Medical College of Fudan University, Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai, People's Republic of China

Received 16 February 2004/ Accepted 8 June 2004

Coxsackievirus group B type 3 (CVB3) is an important cause of viral myocarditis. The infiltration of mononuclear cells into the myocardial tissue is one of the key events in viral myocarditis. Immediately after CVB3 infects the heart, the expression of chemokine(s) by infected myocardial cells may be the first trigger for inflammatory infiltration and immune response. However, it is unknown whether CVB3 can induce the chemokine expression in cardiac myocytes. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemokine that stimulates the migration of mononuclear cells. The objective of the present study was to investigate the effect of CVB3 infection on MCP-1 expression in murine cardiac myocytes and the role of MCP-1 in migration of mononuclear cells in viral myocarditis. Our results showed that the expression of MCP-1 was significantly increased in cardiac myocytes after wild-type CVB3 infection in a time- and dose-dependent manner, which resulted in enhanced migration of mononuclear cells in mice with viral myocarditis. The migration of mononuclear cells was partially abolished by antibodies specific for MCP-1 in vivo and in vitro. Administration of anti-MCP-1 antibody prevented infiltration of mononuclear cells bearing the MCP-1 receptor CCR2 in mice with viral myocarditis. Infection by UV-irradiated CVB3 induced rapid and transient expression of MCP-1 in cardiac myocytes. In conclusion, our results indicate that CVB3 infection stimulates the expression of MCP-1 in myocardial cells, which subsequently leads to migration of mononuclear cells in viral myocarditis.

* Corresponding author. Mailing address: Department of Immunology, Shanghai Medical College of Fudan University, 138 YiXueYuan Rd., Shanghai 200032, People's Republic of China. Phone and fax: 86-21-54237749. E-mail: sdxiong{at}shmu.edu.cn.

{dagger} Present address: First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.

Journal of Virology, November 2004, p. 12548-12556, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12548-12556.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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