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Open Access Research

Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B virus in animal model

Jie Dai123, En-Qiang Chen12, Lang Bai12, Dao-Yin Gong4, Qiao-Ling Zhou12, Xing Cheng12, Fei-Jun Huang4* and Hong Tang12*

Author Affiliations

1 Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China

2 Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China

3 Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041, China

4 Department of Forensic Pathology, Medical School of Basic and Forensic Sciences, Sichuan University, Chengdu, Sichuan, 610041, China

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Virology Journal 2012, 9:280  doi:10.1186/1743-422X-9-280

Published: 21 November 2012

Abstract

Background

The effects of Hepatitis B virus (HBV) rtA181T/sW172* mutation on viral replication and pathogenicity was concerned recently. This study aimed to investigate the biological characteristics of rtA181T/sW172* mutant strain of HBV in animal model.

Methods

The rtA181T/sW172* mutant plasmid was constructed using the pHBV4.1 (wild type HBV) as a template. The wild and mutant HBV replication mouse models were established utilizing a hydrodynamic technique. The titers of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and HBV DNA in serum, and the levels of HBsAg, hepatitis B core antigen(HBcAg), HBV DNA replication intermediates (HBV DNA RI) and HBV RNA in liver were measured after 1, 3, 5, 7, 10, 12 and 15 days of plasmid injection.

Results

In wild-type HBV replication mouse model, serum HBsAg was high on day 1, 3, and 5, but became lower since day 7; while in mutant HBV mouse model, serum HBsAg was always at very low level. In liver tissues, HBV DNA RI of wild type HBV was detected on day 1 after transfection. The level subsequently peaked on day 3, gradually declined after day 5, and was almost undetectable on day 10. However, the HBV DNA RI levels of the mutant strain were always higher and lasted longer until day 15. Consistently, the expression levels of HBsAg and HBcAg in liver of the mutant group were significantly increased.

Conclusions

In the case of the HBV rtA181T/sW172* mutation, the secretion of serum HBsAg was impaired, whereas HBV DNA replication and HBsAg/HBcAg expression were increased in liver. These results suggest that the mutation can impair HBsAg secretion, and may cause the accumulation of viral core particles in liver.

Keywords:
Hepatitis B virus; rtA181T/sW172* mutation; Transcription and replication; Hepatitis B surface antigen; Secretion defect; Drug sensitivity