Pathologic and immunologic characteristics of coxsackievirus A16 infection in rhesus macaques

Pathologic and immunologic characteristics of coxsackievirus A16 infection in rhesus macaques
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DOI:
10.1016/j.virol.2016.10.031
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发表时间:
2017-01-01
期刊:
影响因子:
3.7
通讯作者:
Li, Qihan
Li, Qihan
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Jingjing;Zhang, Ying;Li, Qihan

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柯萨奇病毒A16(CV-A16)是引起人类手足口病的主要病毒,但其致病机制尚不清楚。在恒河猴中,CV-A16感染引起口腔粘膜和四肢中的特征性囊泡以及组织中的病毒血症和阳性病毒载量,表明这些动物反映了感染的病理过程。免疫学分析表明免疫应答缺陷,包括在感染CV-A16的猕猴中检测不到中和抗体和IFN-γ特异性记忆T细胞。此外,尽管存在针对病毒抗原的阳性T细胞记忆应答,但用灭活疫苗免疫的猕猴中现有的中和抗体令人惊讶地不能保护免受病毒攻击。该病毒能够感染前常规树突状细胞并在其中复制,这可能与在动物中观察到的免疫学特征相关。
Coxsackievirus A16 (CV-A16) causes human hand, foot and mouth disease, but its pathogenesis is unclear. In rhesus macaques, CV-A16 infection causes characteristic vesicles in the oral mucosa and limbs as well as viremia and positive viral loads in the tissues, suggesting that these animals reflect the pathologic process of the infection. An immunologic analysis indicated a defective immune response, which included undetectable neutralizing antibodies and IFN-gamma-specific memory T-cells in macaques infected with CV-A16. Furthermore, existing neutralizing antibodies in macaques immunized with the inactivated vaccine were surprisingly unable to protect against a viral challenge despite the presence of a positive T-cell memory response against viral antigens. The virus was capable of infecting pre-conventional dendritic cells and replicating within them, which may correlate with the immunological characteristics observed in the animals.