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人源 SCARB2 转基因小鼠作为肠道病毒 71 型的感染动物模型。

Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71.

机构信息

Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

出版信息

PLoS One. 2013;8(2):e57591. doi: 10.1371/journal.pone.0057591. Epub 2013 Feb 25.

DOI:10.1371/journal.pone.0057591
PMID:23451246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3581494/
Abstract

Enterovirus 71 (EV71) and coxsackievirus (CVA) are the most common causative factors for hand, foot, and mouth disease (HFMD) and neurological disorders in children. Lack of a reliable animal model is an issue in investigating EV71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. We generated a novel EV71-infectious model with hSCARB2-transgenic mice expressing the discovered receptor human SCARB2 (hSCARB2). The challenge of hSCARB2-transgenic mice with clinical isolates of EV71 and CVA16 resulted in HFMD-like and neurological syndromes caused by E59 (B4) and N2838 (B5) strains, and lethal paralysis caused by 5746 (C2), N3340 (C4), and CVA16. EV71 viral loads were evident in the tissues and CNS accompanied the upregulated pro-inflammatory mediators (CXCL10, CCL3, TNF-α, and IL-6), correlating to recruitment of the infiltrated T lymphocytes that result in severe diseases. Transgenic mice pre-immunized with live E59 or the FI-E59 vaccine was able to resist the subsequent lethal challenge with EV71. These results indicate that hSCARB2-transgenic mice are a useful model for assessing anti-EV71 medications and for studying the pathogenesis induced by EV71.

摘要

肠道病毒 71 型（EV71）和柯萨奇病毒（CVA）是引起手足口病（HFMD）和儿童神经紊乱的最常见病原体。由于缺乏可靠的动物模型，难以研究 EV71 诱导的人类疾病表现，目前的临床治疗方法也是对症治疗。我们通过表达已发现的受体人 SCARB2（hSCARB2）的 hSCARB2 转基因小鼠，建立了一种新型 EV71 感染模型。用临床分离的 EV71 和 CVA16 感染 hSCARB2 转基因小鼠，导致由 E59（B4）和 N2838（B5）株引起的类似 HFMD 和神经综合征，以及由 5746（C2）、N3340（C4）和 CVA16 引起的致命性瘫痪。EV71 病毒载量在组织和中枢神经系统中明显增加，同时促炎介质（CXCL10、CCL3、TNF-α和 IL-6）上调，与浸润的 T 淋巴细胞募集有关，导致严重疾病。用活 E59 或 FI-E59 疫苗预先免疫的转基因小鼠能够抵抗随后的 EV71 致命性攻击。这些结果表明，hSCARB2 转基因小鼠是评估抗 EV71 药物和研究 EV71 诱导的发病机制的有用模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00a1/3581494/60764bc55a36/pone.0057591.g009.jpg
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