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

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.