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Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

Qi Wang1, Paul Schwarzenberger2, Fang Yang1, Jingjing Zhang1, Jianjia Su1, Chun Yang1, Ji Cao1, Chao Ou1, Liang Liang1, Junlin Shi1, Fang Yang1, Duoping Wang1, Jia Wang1, Xiaojuan Wang1, Ping Ruan1 and Yuan Li1*

Author Affiliations

1 Department of Experimental Pathology, Guangxi Cancer Institute (Guangxi Tumor Hospital), Nanning 530021, China

2 Quantum Immunologics, Tampa, FL, USA

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Virology Journal 2012, 9:170  doi:10.1186/1743-422X-9-170

Published: 23 August 2012

Abstract

Background

Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period.

Results

Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228) weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew.

Conclusions

Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.

Keywords:
Tree shrew (Tupaia); Hepatitis B virus; Chronic infection