Department of Cellular Biology, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, China.
PLoS One. 2010 Feb 11;5(2):e9160. doi: 10.1371/journal.pone.0009160.
A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77-79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection.
Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination.
Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation.
These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis.
最近的一项研究表明，中国养殖的家兔携带一种新型戊型肝炎病毒（HEV）基因型。尽管兔 HEV 分离株与哺乳动物 HEV 基因型 1 至 4 的核苷酸同源性为 77-79%，但其基因组组织非常相似。由于家兔广泛用于实验，包括作为感染模型，因此我们研究了它们是否构成人类 HEV 感染的合适动物模型。
将 42 只 SPF 兔随机分为 11 组，用 6 种不同的兔 HEV 分离株、2 种不同剂量的第二代兔 HEV 以及基因型 1 和 4 HEV 进行接种。接种后每周采集血清和粪便。检测血清中 HEV 抗原、RNA、抗体和丙氨酸氨基转移酶，检测粪便中 HEV RNA。剖检时采集肝脏样本进行组织病理学检查。
接种兔 HEV 的兔子感染了 HEV，出现病毒血症、粪便病毒排出和血清中病毒抗原水平升高，并发生肝炎，肝酶 ALT 升高。疾病的严重程度与感染剂量（基因组当量）相对应，最严重的肝疾病由 GDC54-18 株引起。然而，只有 9 只感染基因型 4 HEV 的兔子中的 2 只，以及没有感染基因型 1 HEV 的兔子发生肝炎，尽管 9 只接种基因型 1 HEV 的兔子中的 6 只和所有接种基因型 4 HEV 的兔子在接种后 14 周均转化为抗 HEV IgG 抗体阳性。
这些数据表明，家兔是兔 HEV 感染的合适模型，但不太可能用于研究人类 HEV。兔 HEV 感染家兔可能为研究 HEV 发病机制提供合适的平行动物模型。
