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

Abstract

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 antiinflammatory 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.

Coxsackievirus A16 infection stimulates imbalances of T cells in children

“…These data suggest that the viral loads in throat swabs or stool specimens may not correlate with several T-cell subsets as well as the immune factors in plasma. Lin et al reported that the changes in T-cell subsets exhibited a tissue-specific profile (27). They confirmed that throat swab and stool specimens showed a reduced viral load of EV71 than the specific tissue that is the focus of infection, and thus are not adequate for diagnosis.…”

Experimental studies on infant <I>Tupaia belangeri chineses</I> with EV71 infection

“…是手足口病的主要致病原之一, 可使患者并发中枢 神经系统疾病和相关心肺功能衰竭等临床症状, 严 重威胁世界各地婴、幼儿的生命健康，目前尚无有 效药物或疫苗。建立合适的动物模型是深入基础研 究和进行药物评价的关键之一。国内外已有 EV71 感染小鼠的报道, 先后建立了乳鼠 (Lin et al, 2009) 和成年小鼠 (Duo et al, 2009 …”

Dominant CD4‐dependent RNA‐dependent RNA polymerase‐specific T‐cell responses in children acutely infected with human enterovirus 71 and healthy adult controls

“…The cellular and humoral immune responses, such as represented by T cells and the interleukin-6 (IL-6) driven response, are both essential for decreasing the viral load and mortality in EV71-infected mice. 12,13 In humans, an extensive peripheral and central nervous system inflammatory response, with abnormal IL-10, IL-13 and interferon-c (IFN-c) cytokine production as well as lymphocyte depletion, appears to be responsible for the pathogenesis of EV71-associated pulmonary oedema. [14][15][16] However, to date the mechanism of the cellular immune response to EV71 has not been elucidated in detail.…”

“…Blood samples were obtained on days 1-7 after onset, discharge from the hospital (day [7][8][9][10][11][12][13][14] and the fully recovered stage (defined as 1 month after illness onset), respectively. All samples were collected specifically for this study and were coded to protect confidentiality.…”