戊型肝炎病毒实验感染恒河猴的研究

Study on Experimental Infection of Rhesus Monkeys with Hepatitis E Virus

报道了用戊型肝炎（ＨｅｐａｔｉｔｉｓＥ，ＨＥ）病人粪便悬液感染恒河猴后的组织病理学、血液生化与免疫学以及病毒学分子生物学检测的结果。三只实验猴在感染后第３～４周均出现ＡＬＴ异常；粪便以及肝脏与胆囊组织超薄切片中电镜观察到２７～３４ｎｍ大小的病毒样颗粒；病理组织切片观察表明，肝脏组织有典型的急性炎症病灶；粪便与血清经ＲＴｎＰＣＲ扩增到戊型肝炎病毒（ＨｅｐａｔｉｔｉｓＥＶｉｒｕｓ，ＨＥＶ）特异性片段，粪便排毒从感染后第７天持续至第５０天左右，病毒血症迟于粪便排毒，出现于感染后两周左右，维持１～２周；ＥＬＩＳＡ检测发现，实验猴血清中ＨＥＶＩｇＧ抗体水平在感染后３～４周阳转，４～５个月后转阴。这些实验结果提示，恒河猴作为ＨＥＶ感染实验动物模型是理想的，建立系统的恒河猴实验模型对探讨ＨＥＶ感染发病机理、机体免疫应答以及临床诊断与疫苗研制具有重要意义。

Three rhesus monkeys ( Macaca mulatta ) were inoculated intravenously with fecal suspensions obtained from hepatitis E patients. The alanine aminotransferase (ALT) level in the three monkeys elevated 3 to 4 weeks after infection. Virus like particles about 27 to 34 nm were found in the stool specimens, the liver and the gallbladder tissues by electron microscope examination. The liver tissue slice showed characteristic histopathologic changes of acute hepatitis. Specific HEV fragments were obtained by RT nPCR from feces and sera. Excretion of virus began on the 7th day and lasted to about the 50th day after infection. The appearance of virus in serum was 2 weeks after inoculation and lasted for only 1 to 2 weeks. Anti HEV IgG was detected by enzyme linked immunosorbent assay 3-4 weeks after infection and negative conversion took place 4 to 5 months later.