Systematic pathogenesis and replication of avian hepatitis E virus in specific-pathogen-free adult chickens
Systematic pathogenesis and replication of avian hepatitis E virus in specific-pathogen-free adult chickens
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DOI：
10.1128/jvi.79.6.3429-3437.2005
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Meng, XJ
中科院分区：
文献类型：
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作者：
Billam, P;Huang, FF;Meng, XJ
戊型肝炎病毒(HEV)是人类重要的病原体。由于缺乏HEV的细胞培养系统和实用的动物模型，对其致病机制和复制机制知之甚少。在鸡身上发现了一种HEV毒株，命名为禽类HEV，这促使我们评估鸡作为研究HEV的模型。将85只60周龄无特定病原体的雏鸡随机分为3组。第1组(28只)经口鼻腔接种5×10(4.5)50%禽流感病毒感染量；第2组(29只)静脉注射相同剂量的鸡戊型肝炎病毒。3组鸡(n=28)不接种，作为对照。在接种后1、3、5、7、10、13、16、20、24、28、35和42天，每组各取2只鸡进行尸检，其余鸡在接种后56天剖检。每次尸检时都采集血清、粪便和各种组织样本，包括肝和脾样本，以进行病理和病毒学测试。到21dpi，全部经口鼻和静脉注射。免疫后的鸡出现了血清转换。从1-20dpi的静脉注射中可以不同地检测到粪便病毒的脱落。口鼻组为10~56dpi。在两种静脉注射的血清、胆汁和肝脏样本中都检测到了禽HEV RNA。并经口鼻接种鸡只。鼻腔28例中有7例和静脉注射29例中7例可见以包膜下出血或右中间叶增大为特征的大体肝损害。给鸡接种疫苗。肝脏镜下病变主要为淋巴细胞性外周静脉炎和静脉炎。口鼻(P=0.0008)和静脉注射的病变评分较高。(P=0.0029)组鸡显著高于对照组(P=0.05)。感染鸡的血浆肝酶乳酸脱氢酶略有升高。结果表明，鸡是研究HEV复制和致病的有效模型。这是首次报道HEV在同源动物模型中通过其自然途径传播。
Hepatitis E virus (HEV) is an important human pathogen. Due to the lack of a cell culture system and a practical animal model for HEV, little is known about its pathogenesis and replication. The discovery of a strain of HEV in chickens, designated avian HEV, prompted us to evaluate chickens as a model for the study of HEV. Eighty-five 60-week-old specific-pathogen-free chickens were randomly divided into three groups. Group 1 chickens (n = 28) were each inoculated with 5 x 10(4.5) 50% chicken infectious doses of avian HEV by the oronasal route, group 2 chickens (n = 29) were each inoculated with the same dose by the intravenous (i.v.) route, and group 3 chickens (n = 28) were not inoculated and were used as controls. Two chickens from each group were necropsied at 1, 3, 5, 7, 10, 13, 16, 20, 24, 28, 35, and 42 days postinoculation (dpi), and the remaining chickens were necropsied at 56 dpi. Serum, fecal, and various tissue samples, including liver and spleen samples, were collected at each necropsy for pathological and virological testing. By 21 dpi, all oronasally and i.v. inoculated chickens had seroconverted. Fecal virus shedding was detected variably from 1 to 20 dpi for the i.v. group and from 10 to 56 dpi for the oronasal group. Avian HEV RNA was detected in serum, bile, and liver samples from both i.v. and oronasally inoculated chickens. Gross liver lesions, characterized by subcapsular hemorrhages or enlargement of the right intermediate lobe, were observed in 7 of 28 oronasally and 7 of 29 i.v. inoculated chickens. Microscopic liver lesions were mainly lymphocytic periphlebitis and phlebitis. The lesion scores were higher for oronasal (P = 0.0008) and i.v. (P = 0.0029) group birds than for control birds. Slight elevations of the plasma liver enzyme lactate dehydrogenase were observed in infected chickens. The results indicated that chickens are a useful model for studying HEV replication and pathogenesis. This is the first report of HEV transmission via its natural route in a homologous animal model.