Lymphocyte and antibody responses reduce enterovirus 71 lethality in mice by decreasing tissue viral loads.
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.
Lin
Yu-Wen
YW
Institute of Biomedical Sciences, National Cheng Kung University, Tainan, Taiwan 701, Republic of China.
Chang
Kung-Chao
KC
Kao
Chia-Min
CM
Chang
Shih-Ping
SP
Tung
Yuk-Ying
YY
Chen
Shun-Hua
SH
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D001921:Brain / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D002648:Child; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000276:immunology / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009500:Neutralization Tests; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D019562:Viral Load
D000914:Antibodies, Viral