人柯萨奇B2病毒感染恒河猴模型的初步研究

Preliminary study on the infection of rhesus monkeys by human coxsackie B2 virus

目的通过对人柯萨奇B2病毒经口腔感染恒河猴婴猴的感染特征进行初步分析研究,为人柯萨奇B2病毒恒河猴感染模型的建立提供实验方法及技术支持,为后续开展其感染机制、病理生理等研究奠定基础。方法将柯萨奇B2病毒经口腔感染方式感染3~4月龄的恒河猴婴猴,观察记录恒河猴临床症、体温;采集血液检测生理生化指标;血样和疱疹检测病毒;疱疹组织进行病理检测。结果恒河猴感染后2~5 d出现手、足、口疱疹;动物出现精神沉郁、活动及饮食量减少的情况;体温呈现稽留热曲线图;疱疹液和血样中都可检测到柯萨奇B2病毒;血常规检测出现白细胞减少、单核细胞增加、淋巴细胞数量减少、粒细胞数量增加、嗜酸性细胞增加、嗜碱性细胞减少的情况。血液生化检测发现肝功、肾功、心肌酶都发生了不同程度的升高;疱疹组织病理学显示恒河猴疱疹呈鳞状上皮增厚,表面角化过度,局部坏死伴炎细胞浸润,脓肿形成。结论人柯萨奇B2病毒感染婴猴后出现一系列较为特征的手足口疱疹、临床症状、生理生化、病毒血症等情况,表明经口腔感染方式恒河猴婴猴可以成功构建柯萨奇B2病毒感染的动物模型,建立的相关检测方法和技术是可行的,为后续建立开展恒河猴柯萨奇B2病毒感染模型、发病机制研究、药物及疫苗的评价奠定了实验基础。

Objective To provide experimental method and technical support for the establishment of a rhesus monkey model of human Coxsackie B2 virus infection for analyzing the infection characteristics of human Coxsackie B2 virus in rhesus monkey models.Methods Coxsackie B2 virus was inoculated orally to infect infant rhesus monkeys aged 3-4 months.The clinical symptoms,body weight and temperature of the rhesus monkeys were observed.Blood was collected to detect physiological and biochemical indexes.Virus titers were analyzed in the blood and herpes tissues.Herpes tissues were pathologically examined.Results Herpes appeared on the hands,feet and mouth 2-5 days after infection;animals showed depression,decreased activity and diet intake.Coxsackie B2 virus was detected in the herpes and serum samples.Rhesus monkeys infected with the virus routinely developed leukopenia,and had increased numbers of monocytes,granulocytes,and eosinophils,but decreased numbers of lymphocytes and basophils.Blood biochemical tests showed that the liver function,kidney function,and myocardial enzymes were more or less increased.Herpes histopathology indicated that the tissues had squamous epithelial thickening,excessive surface hyperkeratosis,local necrosis with inflammatory cell infiltration,and abscess formation.Conclusions Characteristic effects of viral infection in infant monkeys including hand,foot and mouth herpes,clinical symptoms,physiological and biochemical impairments,and viremia,indicating that the rhesus monkeys were successfully infected with Coxsackie B2 virus orally.The established detection method and techniques used were feasible for this type of study and laid an experimental foundation for the subsequent establishment of a model of rhesus Coxsackie B2 virus infection for pathogenesis research and drug and vaccine evaluation.