Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, China.
Medical School, Kunming University of Science and Technology, 727 Jingming Road, Kunming, China.
BMC Infect Dis. 2018 Dec 20;18(1):687. doi: 10.1186/s12879-018-3544-4.
Hepatitis E virus (HEV) is a leading cause of hepatitis worldwide. However, its infection biology and pathogenesis remain largely elusive. Furthermore, no proven medication is available for treating hepatitis E. Robust experimental models are urgently required to advance the research of HEV infection. Because of the lacking of a sophisticated small animal model, this study aimed to establish a mouse model of HEV infection.
We constructed a full-length swine HEV cDNA clone of genotype 4 (named as pGEM-HEV) by reverse genetics approach. And we inoculated with HEV RNA in BALB/c mice to establish small animal model for HEV infection and pathogenesis studies.
The capped RNA transcripts of pGEM-HEV prepared in vitro were replication-competent in HepG2 cells. Importantly, BALB/c mice intravenously inoculated with RNA transcripts of pGEM-HEV developed an active infection as shown by shedding viruses in feces, detectable negative strand of HEV in the liver, spleen and kidney, and causing liver inflammation.
In this study, we successfully established of BALB/c mice-based small animal model for HEV provides an opportunity to further understand HEV pathogenesis and to develop effective antiviral medications.
戊型肝炎病毒（HEV）是全球范围内肝炎的主要病因。然而，其感染生物学和发病机制在很大程度上仍难以捉摸。此外，尚无有效的药物可用于治疗戊型肝炎。迫切需要建立强大的实验模型来推进 HEV 感染的研究。由于缺乏复杂的小动物模型，本研究旨在建立 HEV 感染的小鼠模型。
我们通过反向遗传学方法构建了全长猪 HEV 基因型 4 cDNA 克隆（命名为 pGEM-HEV）。我们用 HEV RNA 感染 BALB/c 小鼠，以建立用于 HEV 感染和发病机制研究的小动物模型。
体外制备的 pGEM-HEV 帽状 RNA 转录本在 HepG2 细胞中具有复制能力。重要的是，静脉内接种 pGEM-HEV RNA 转录本的 BALB/c 小鼠表现出活跃的感染，表现为粪便中排出病毒、肝脏、脾脏和肾脏中可检测到的 HEV 负链以及引起肝脏炎症。
本研究成功建立了基于 BALB/c 小鼠的 HEV 小动物模型，为进一步了解 HEV 的发病机制和开发有效的抗病毒药物提供了机会。
