A systematic study of Tupaia as a model for human acute hepatitis B infection

The Journal of Veterinary Medical Science

article

Jun LI¹  Tong-Dong SHI²  Jun-Feng HAN¹  Xing-Guang ZENG³  Cui-Li FAN³  Chao HAN¹  Hong-Li LIU³  Yu-Zhang WU¹ 

[1] Institute of Immunology, Third Military Medical University;Division of Infectious Diseases, The Second Affiliated of Chongqing University of Medical Science;Ltd.

关键词: acute infection;    hepatitis B virus;    pathogenesis;    small animal model;    viral replication;   

DOI  :  10.1292/jvms.21-0026

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

The molecular features of hepatitis B virus (HBV) infection, eradication, and pathogenesis are poorly understood, partly due to the lack of an adequate animal model that faithfully reproduces the course of infection. Although Tupaia belangeri were previously recognized as HBV-susceptible animals, the course of infection in adult tupaias remains obscure. Herein, we performed a longitudinal study and demonstrated that adult tupaias were efficiently infected (90% infection rate) with 10 8 copies of the HBV genome. HBV replicated vigorously, produced high levels of covalently closed circular DNA (cccDNA) in hepatocytes, and released hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAg), and HBV DNA into the serum at day 9 post-inoculation (p.i.), which then decreased on day 15 p.i. The kinetics were consistent with the expression of liver HBsAg and HBeAg, as determined with immunohistochemistry. The viral products in serum at day 9 and 15 p.i. represented de novo synthesized viral products, as treatment with a viral entry inhibitor completely abolished these products from the serum. Viral clearance and serological conversion occurred at day 21 p.i. and were accompanied by elevated alanine transaminase (ALT) levels and liver pathology, such as inflammatory infiltration and hepatocyte ballooning degeneration. Although ALT levels eventually returned to normal levels by day 42 p.i., the liver pathology persisted until at least day 120 p.i. The HBV infection process in tupaia, therefore, exhibits features similar to that of human acute HBV infection, including viral replication, viral eradication, ALT elevation, and liver pathology. Thus, adopting the tupaia model to study host-HBV interactions presents an important advance which could facilitate further investigation and understanding of human HBV infection, especially for features like cccDNA that current small-animal models cannot effectively model.

【 授权许可】

Unknown