Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Division of Experimental Animals Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Viruses. 2022 May 24;14(6):1125. doi: 10.3390/v14061125.
Although cell culture systems for hepatitis E virus (HEV) have been established by using cell lines such as PLC/PRF/5 and A549, small-animal models for this virus are limited. Since Mongolia gerbils are susceptible to genotype 1, 3 and 4 HEV (HEV-1, HEV-3 and HEV4), we intraperitoneally inoculated Mongolia gerbils with HEV-5, HEV-7, HEV-8, rabbit HEV or rat HEV in addition to the above three genotypes to investigate the infectivity and to assess whether Mongolia gerbil is an appropriate animal model for HEV infection. The results indicated that (i) HEV-5 and rat HEV were effectively replicated in the Mongolia gerbils in the same manner as HEV-4: large amounts of the viral RNA were detected in the feces and livers, and high titers of the serum anti-HEV IgG antibodies were induced in all animals. The feces were shown to contain HEV that is infectious to naïve gerbils. Furthermore, HEV-4, HEV-5 and rat HEV were successfully transmitted to the gerbils by oral inoculation. (ii) Although the viral RNA and serum anti-HEV IgG antibodies were detected in all animals inoculated with HEV-1 and HEV-8, both titers were low. The viral RNA was detected in the feces collected from two of three HEV-3-inoculated, and one of three HEV-7-inoculated gerbils, but the titers were low. The serum antibody titers were also low. The viruses excreted into the feces of HEV-1-, HEV-3-, HEV-7- and HEV-8-inoculated gerbils failed to infect naïve Mongolia gerbils. (iii) No infection sign was observed in the rabbit HEV-inoculated gerbils. These results demonstrated that Mongolia gerbils are broadly susceptible to HEV, and their degree of sensitivity was dependent on the genotype. Mongolia gerbils were observed to be susceptible to not only HEVs belonging to HEV-A but also to rat HEV belonging to HEV-C1, and thus Mongolia gerbil could be useful as a small-animal model for cross-protection experiments between HEV-A and HEV-C1. Mongolia gerbils may also be useful for the evaluation of the efficacy of vaccines against HEV.
虽然已经建立了使用 PLC/PRF/5 和 A549 等细胞系的戊型肝炎病毒 (HEV) 细胞培养系统,但该病毒的小动物模型仍然有限。由于蒙古沙鼠易感染基因型 1、3 和 4 的 HEV(HEV-1、HEV-3 和 HEV4),我们除了上述三种基因型之外,还通过腹腔接种蒙古沙鼠 HEV-5、HEV-7、HEV-8、兔 HEV 或大鼠 HEV,以研究其感染性,并评估蒙古沙鼠是否为合适的 HEV 感染动物模型。结果表明:(i) HEV-5 和大鼠 HEV 以与 HEV-4 相同的方式在蒙古沙鼠中有效复制:大量病毒 RNA 在粪便和肝脏中被检测到,所有动物均诱导出高滴度的血清抗-HEV IgG 抗体。粪便中含有可感染新生沙鼠的 HEV。此外,通过口服接种,成功地将 HEV-4、HEV-5 和大鼠 HEV 传播给沙鼠。(ii) 虽然所有接种 HEV-1 和 HEV-8 的动物均检测到病毒 RNA 和血清抗-HEV IgG 抗体,但滴度均较低。从三分之二的 HEV-3 接种沙鼠和三分之一的 HEV-7 接种沙鼠的粪便中检测到病毒 RNA,但滴度较低。血清抗体滴度也较低。HEV-1、HEV-3、HEV-7 和 HEV-8 接种沙鼠排出的病毒未能感染新生蒙古沙鼠。(iii) 接种兔 HEV 的沙鼠未出现感染迹象。这些结果表明,蒙古沙鼠广泛易感 HEV,其敏感性程度取决于基因型。蒙古沙鼠不仅易感染属于 HEV-A 的 HEV,还易感染属于 HEV-C1 的大鼠 HEV,因此蒙古沙鼠可作为 HEV-A 和 HEV-C1 之间交叉保护实验的小动物模型。蒙古沙鼠也可用于评估抗 HEV 疫苗的功效。