An Immunocompetent Mongolian Gerbil Model for Hepatitis E Virus Genotype 1 Infection.

Hepatitis E virus (HEV), primarily genotype 1 (HEV-1), causes approximately 20.1 million infections, 44,000 deaths, and 3000 stillbirths annually. Current evidence indicates that HEV-1 is only transmitted in humans. Here, we evaluated whether Mongolian gerbils can serve as animal models for HEV-1 infection. Mongolian gerbils were used for HEV-1 and hepatitis E virus genotype 3 infection experiments. HEV infection parameters, including detection of HEV RNA and HEV antigen, liver function assessment, and histopathology, were evaluated. We adapted a clinical isolate of HEV-1 for Mongolian gerbils by serial passaging in feces of aged male gerbils. The gerbil-adapted strain obtained at passage 3 induced a robust, acute HEV infection, characterized by stable fecal virus shedding, elevated liver enzymes, histopathologic changes in the liver, and seroconversion to anti-HEV. An infectious complementary DNA clone of the adapted virus was generated. HEV-1-infected pregnant gerbils showed a high rate of maternal mortality and vertical transmission. HEV RNA or antigens were detected in the liver, kidney, intestine, placenta, testis, and fetus liver. Liver and placental transcriptomic analyses indicated activation of host immunity. Tacrolimus prolonged HEV-1 infection, whereas ribavirin cleared infection. The protective efficacy of a licensed HEV vaccine was validated using this model. HEV-1 efficiently infected Mongolian gerbils. This HEV-1 infection model will be valuable for investigating hepatitis E immunopathogenesis and evaluating vaccines and antivirals against HEV. Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.

Citation

Tianxu Liu, Qiyu He, Xinyue Yang, Yuebao Li, Disen Yuan, Qinghui Lu, Tianyu Tang, Guiwen Guan, Liwei Zheng, He Zhang, Changyou Xia, Xin Yin, Guochao Wei, Xiangmei Chen, Fengmin Lu, Lin Wang. An Immunocompetent Mongolian Gerbil Model for Hepatitis E Virus Genotype 1 Infection. Gastroenterology. 2024 Sep;167(4):750-763.e10

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PMID: 38582270

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