Antibody dependent enhancement infection of enterovirus 71 in vitro and in vivo.

Antibody dependent enhancement infection of enterovirus 71 in vitro and in vivo.
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肠道病毒71型体外和体内抗体依赖性增强感染

DOI:
10.1186/1743-422x-8-106
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发表时间:
2011-03-08
期刊:
影响因子:
4.8
通讯作者:
Qin CF
Qin CF
中科院分区:
医学3区
文献类型:
--
作者:
Han JF;Cao RY;Deng YQ;Tian X;Jiang T;Qin ED;Qin CF

文献摘要

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人类肠道病毒71型(EV71)已成为急性脑炎和幼儿死亡的重要原因。EV71引起的临床表现多种多样,从轻微的手足口病到严重的神经系统并发症和死亡,但其发病机制仍不清楚。抗体依赖性增强(ADE)感染已在各种病毒中被报道,并已被证明有助于疾病的严重程度。在这项研究中,亚中和抗体的存在增强了THP-1细胞中EV71的感染,并在乳鼠模型中增加了EV71感染的死亡率。此外,建立了一个继发感染模型来描述ADE与疾病严重程度之间的关系,结果表明,初发无症状EV71感染会增加乳鼠继发EV71感染的死亡率。总之,这些体外和体内实验有力地支持了EV71感染ADE的假说。目前的研究结果表明,ADE可能参与了EV71严重感染的发病机制,并提出了疫苗开发和抗体治疗的实际问题。
Human enterovirus 71 (EV71) has emerged as a significant cause of acute encephalitis and deaths in young children. The clinical manifestations caused by EV71 varied from mild hand, foot and mouth disease to severe neurological complications and deaths, but its pathogenesis remains elusive. Antibody dependent enhancement (ADE) infection has been reported in various viruses and has been shown to contribute to disease severity. In this study, the presence of sub-neutralizing antibody was demonstrated to enhance EV71 infection in THP-1 cells and increase the mortality of EV71 infection in a suckling mouse model. Further, a secondary infection model was established to characterize the correlation between ADE and disease severity, and primary asymptomatic EV71 infection was shown to increase the mortality of the secondary EV71 infection in suckling mice. Together, these in vitro and in vivo experiments strongly supported the hypothesis of ADE infection of EV71. The present findings indicate ADE might contribute to the pathogenesis of severe EV71 infection, and raise practical issues of vaccine development and antibody-based therapy.