柯萨奇病毒A组6型和B组1型混合感染叙利亚金黄地鼠动物模型的实验研究
作者:
作者单位:

1.中国医学科学院/北京协和医学院  2. 3.医学生物学研究所

基金项目:

北京协和医学院中央高校基本科研业务费(3332023079);云南省基础研究专项-面上项目(202401CF070048);中国医学科学院医学生物学研究所所级重点科研专项项目(No.2022IMBCAMS002)


Coinfection of Coxsackievirus A6 and B1 Experimental Study on Syrian Hamsters Animal Model
Author:
Affiliation:

Institute of Medical Biology,Chinese Academy of Medical Sciences

Fund Project:

Basic Research Funds for Central Universities of Peking Union Medical College(3332023079);Basic Research Project of Science and Technology Plan of Yunnan Provincial Department of Science and Technology(202401CF070048);Key Research Project of the Institute of Medical Biology, Chinese Academy of Medical Sciences (No.2022IMBCAMS002)

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    摘要:

    目的 建立柯萨奇病毒A组6型(Coxsackievirus A6, CVA6)和B组1型(Coxsackievirus B1, CVB1)混合感染叙利亚金黄地鼠手足口病动物模型。方法 本研究将24只地鼠分为CVA6感染组、CVB1感染组、CVA6和CVB1混合感染组及对照组,采取鼻腔滴注病毒液和PBS方式造模。监测记录15天内临床指标、生理指标、排毒情况,并在感染后D7选取动物进行组织病理学和病毒抗原与核酸检测。结果 单独和混合感染的实验组地鼠均出现类似人类手足口病的临床症状;WBC、NEUT、LYMPH结果提示病毒感染血象特征;咽拭子、粪便、血液和组织中均能检测到两种病毒核酸;粪便样品中能分离出两种病毒;脑等组织出现病理损伤表现及CVA6和CVB1病毒抗原蛋白和核酸的阳性共定位。结论 经鼻腔同时滴注CVA6和CVB1混合液能够成功感染叙利亚金黄地鼠,复制出类似人类手足口病的疱疹、造成病毒性心肌炎和脑炎病理损伤等,结果显示混合感染组相较于单独感染组病情更为严重,表现为临床症状加重、病毒复制增高以及组织病理损伤明显。本研究为开展人类肠道病毒混合感染基础和临床研究提供一定借鉴和参考。

    Abstract:

    Objective To establish an animal model of hand, foot and mouth disease (HFMD) in Syrian hamsters coinfected with Coxsackievirus A6 (CVA6) and Coxsackievirus B1 (CVB1). Methods Twenty-four Syrian hamsters were divided into CVA6 infection group, CVB1 infection group, CVA6 and CVB1 coinfection group and control group. The model was established by nasal instillation of virus solution and PBS. Clinical indicators, physiological indicators, and detoxification status were monitored and recorded for 15 days, and animals were selected on D7 after infection for histopathology and viral antigen and nucleic acid testing. Results Hamsters in the single and coinfection groups showed clinical symptoms similar to human HFMD. The results of WBC, NEUT and LYMPH indicated the blood characteristics of viral infection. Both viral nucleic acids were detected in throat swabs, feces, blood and tissues. Both viruses were isolated in fecal samples. Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues. Conclusion The nasal instillation of CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters, replicate herpes similar to human hand, foot and mouth disease, and cause viral myocarditis and encephalitis pathological damage. The results showed that the coinfection group was more serious than the single infection group, with worse clinical symptoms, increased viral replication and obvious tissue pathological damage. This study provides a certain reference for the basic and clinical research of human enterovirus coinfection.

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  • 收稿日期:2024-07-22
  • 最后修改日期:2024-09-02
  • 录用日期:2025-02-19
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