Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Viruses. 2024 Oct 12;16(10):1605. doi: 10.3390/v16101605.
Since Mongolian gerbils are broadly susceptible to hepatitis E virus (HEV), including genotypes 1, 4, 5, and 8 (HEV-1, HEV-5, HEV-5, and HEV-8) and rat HEV, they are a useful small animal model for HEV. However, we have observed that the subtypes HEV-3k and HEV-3ra in genotype 3 HEV (HEV-3) were not infected efficiently in the gerbils. A small-animal model for HEV-3 is also needed since HEV-3 is responsible for major zoonotic HEV infections. To investigate whether gerbils can be used as animal models for other subtypes of HEV-3, we injected gerbils with five HEV-3 subtypes (HEV-3b, -3e, -3f, -3k, and -3ra) and compared the infectivity of the subtypes. We detected viral RNA in the gerbils' feces. High titers of anti-HEV IgG antibodies in serum were induced in all HEV-3b/ch-, HEV-3f-, and HEV-3e-injected gerbils. Especially, the HEV-3e-injected animals released high levels of viruses into their feces for an extended period. The virus replication was limited in the HEV-3b/wb-injected and HEV-3k-injected groups. Although viral RNA was detected in HEV-3ra-injected gerbils, the copy numbers in fecal specimens were low; no antibodies were detected in the sera. These results indicate that although HEV-3's infectivity in gerbils depends on the subtype and strain, Mongolian gerbils have potential as a small-animal model for HEV-3. A further comparison of HEV-3e with different genotype strains (HEV-4i and HEV-5) and different genera (rat HEV) revealed different ALT elevations among the strains, and liver damage occurred in HEV-4i- and HEV-5-infected but not HEV-3e- or rat HEV-infected gerbils, demonstrating variable pathogenicity across HEVs from different genera and genotypes in Mongolian gerbils. HEV-4i- and HEV-5-infected Mongolian gerbils might be candidate animal models to examine HEV's pathogenicity.
由于蒙古沙土鼠广泛易感戊型肝炎病毒（HEV），包括基因型 1、4、5 和 8（HEV-1、HEV-5、HEV-5 和 HEV-8）和大鼠 HEV，因此它们是一种有用的戊型肝炎病毒小动物模型。然而，我们观察到，在沙土鼠中，基因型 3 中的 HEV-3k 和 HEV-3ra 亚型不能有效地被感染。由于 HEV-3 是主要的人畜共患 HEV 感染，因此也需要一种戊型肝炎病毒 3 型的小动物模型。为了研究沙土鼠是否可以作为其他 HEV-3 亚型的动物模型，我们用五种戊型肝炎病毒 3 型（HEV-3b、-3e、-3f、-3k 和 -3ra）注射沙土鼠，并比较了这些亚型的感染性。我们在沙土鼠的粪便中检测到了病毒 RNA。在所有用 HEV-3b/ch-、HEV-3f-和 HEV-3e 注射的沙土鼠中，血清中均诱导出了高滴度的抗-HEV IgG 抗体。特别是，用 HEV-3e 注射的动物在较长时间内从粪便中释放出高水平的病毒。在 HEV-3b/wb 注射组和 HEV-3k 注射组中，病毒复制受到限制。尽管在注射 HEV-3ra 的沙土鼠中检测到了病毒 RNA，但粪便标本中的拷贝数较低；血清中未检测到抗体。这些结果表明，尽管 HEV-3 在沙土鼠中的感染性取决于亚型和株，但蒙古沙土鼠具有作为戊型肝炎病毒 3 型小动物模型的潜力。进一步比较 HEV-3e 与不同基因型（HEV-4i 和 HEV-5）和不同属（大鼠 HEV）的株系，发现株系之间的 ALT 升高程度不同，在感染 HEV-4i 和 HEV-5 的沙土鼠中发生了肝损伤，但在感染 HEV-3e 和大鼠 HEV 的沙土鼠中没有发生，这表明在蒙古沙土鼠中不同属和基因型的戊型肝炎病毒具有不同的致病性。感染 HEV-4i 和 HEV-5 的蒙古沙土鼠可能是研究戊型肝炎病毒致病性的候选动物模型。
