甲型肝炎病毒恒河猴模型的评估

Evaluation of Rhesus Monkey as A Model of Hepatitis A Virus Infection

目的 对国产恒河猴作为甲型肝炎病毒 (HAV)的动物模型做出全面评估。方法 用HAV野型株和H2株减毒HAV感染恒河猴 ,检测分析猴体的各种反应。结果 14只恒河猴经 4株野型病毒感染后 ,全部血清抗体阳转 ,效价为 1∶2～ 1∶12 80 ,13只猴 ( 92 .9% )的血清酶异常升高和粪便排毒 ,2只猴 ( 14 .3% )有肝脏组织病理学极轻度改变 ;35 2只恒河猴分组接种 6 8批H2株及其子代病毒后 ,血清抗体阳转率为 99.7% ,血清酶异常升高率为2 .8% ,粪便排毒率为 5 8.3% ( 14 / 2 4 ) ,无肝脏组织病理学变化。结论 国产恒河猴是HAV的敏感动物 ,其ALT等血清酶指标能有效反映HAV的强毒或弱毒性质 。

Objective To completely evaluate the rhesus monkey as a model of hepatitis A virus(HAV)infection.Methods Infect rhesus monkeys with 4 wild strains and 68 lots of attenuated H2 strains of HAV,and analyze the responses of the monkeys.Results The serum antibody positive conversion rate of the 14 monkeys infected with 4 wild strains was 100%,and the antibody titers of them ranged from 1∶2 to 1∶ 1 280 .Of the 14 monkeys,13(92.9%)showed abnormal elevation of serum enzyme and excretion of virus in stools,and 2( 14.3% )showed slight pathological changes in liver tissues.A total of 352 monkeys were inoculated with 68 lots of primary or subcultured H2 strains,and serum antibody positive conversion,abnormal elevation of serum enzyme and excretion of virus in stools were observed in 99.7%,2.8% and 58.3% of them respectively.However,no pathological changes in liver tissues were observed.Conclusion Domestic rhesus monkeys were sensitive to HAV infection,and the serum enzyme levels of them reflected the properties of virulent or attenuated HAV strain effectively.So rhesus monkey can be served as an animal model to monitor the residual virulence of strain used for the production of live attenuated HA vaccine.