Characterization of hepatitis E virus infection in tree shrew (Tupaia belangeri chinensis)

Abstract

Background: Hepatitis E virus (HEV) is a major cause of hepatitis in developing countries and poses a threat to public health worldwide. Tree shrew (Tupaia belangeri chinensis) is a useful animal model in studies on hepatitis viruses, such as hepatitis B and C viruses. However, the use of this animal model for HEV research is yet to be developed. Methods: Tree shrews were intravenously (IV) injected with swine genotype 4 HEV or infected by contact-exposure to IV infected tree shrews. RT-nPCR was performed to detect HEV RNA in the feces, tissues, and blood. HEV capsid protein in the different tissues was detected by Western blot and estimated by quantitative RT-PCR. Anti-HEV antibodies were determined by ELISA. Liver damages were evaluated by histopathologic examination and analysis of liver-specific enzymes activities. Results: Both negative and positive strands of HEV RNA were detected in the feces of the HEV-infected or contact-exposed tree shrews 3-4 days post-inoculation. HEV RNA was detectable in the liver, spleen, kidneys, and bile. Virusemia developed in all the HEV-infected tree shrews. HEV capsid protein was expressed in the liver, spleen, and kidneys. The histological examination and analysis of liver-specific enzymes activities showed that HEV caused acute liver lesions in the tree shrews. Meanwhile, the infected tree shrews showed positive IgG and IgM antibodies. Conclusions: Tree shrews are susceptible to HEV and may be useful animal models for HEV experimental infection studies on pathogenesis or preclinical drug development.