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Journal of Virology, July 2009, p. 6477-6483, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00434-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Lymphocyte and Antibody Responses Reduce Enterovirus 71 Lethality in Mice by Decreasing Tissue Viral Loads{triangledown}

Yu-Wen Lin,1 Kung-Chao Chang,2 Chia-Min Kao,3 Shih-Ping Chang,3 Yuk-Ying Tung,4 and Shun-Hua Chen1,3*

Institute of Biomedical Sciences,1 Department of Pathology,2 Department of Microbiology and Immunology, College of Medicine,3 Statistical Analysis Laboratory, Institute of Education, College of Social Sciences, National Cheng Kung University, Tainan, Taiwan 701, Republic of China4

Received 2 March 2009/ Accepted 16 April 2009

Enterovirus 71 (EV71) infects the central nervous system and causes death and long-term neurological sequelae in hundreds of thousands of young children, but its pathogenesis remains elusive. Immunopathological mechanisms have been suspected to contribute to the pathogenesis of neurological symptoms, so anti-inflammatory agents have been used to treat patients with neurological symptoms. The present study was therefore designed to investigate the functions of lymphocyte and antibody responses in EV71 infection using a mouse model. Immunohistochemical staining analysis revealed virus and three types of lymphocytes, B cells, CD4 T cells, and CD8 T cells, in the spinal cord of an EV71-infected patient who died. A study of mice showed that the levels of virus and lymphocytes in brains and antibody titers in sera were elevated during the time when the mice succumbed to death in a phenomenon analogous to that observed in patients. Further studies demonstrated that after infection, the disease severity, mortality, and tissue viral loads of mice deficient in B, CD4 T, or CD8 T cells were significantly higher than those of wild-type mice. In addition, treatment with a virus-specific antibody, but not a control antibody, before or after infection significantly reduced the disease severity, mortality, and tissue viral loads of mice deficient in B cells. Our results show that both lymphocyte and antibody responses protect mice from EV71 infection. Our study suggests the use of vaccines and virus-specific antibodies to control fatal outbreaks and raises caution over the use of corticosteroids to treat EV71-infected patients with neurological symptoms.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 701, Republic of China. Phone: 886-6-2353535, ext. 5633. Fax: 886-6-2082705. E-mail: shunhua{at}mail.ncku.edu.tw

{triangledown} Published ahead of print on 22 April 2009.

Journal of Virology, July 2009, p. 6477-6483, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00434-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lin, Y.-W., Wang, S.-W., Tung, Y.-Y., Chen, S.-H. (2009). Enterovirus 71 Infection of Human Dendritic Cells. Exp. Biol. Med. 234: 1166-1173 [Abstract] [Full Text]  


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