Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B virus in animal model.
Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B virus in animal model.
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DOI：
10.1186/1743-422x-9-280
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发表时间：
2012-11-21
期刊：
影响因子：
4.8
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Dai J;Chen EQ;Bai L;Gong DY;Zhou QL;Cheng X;Huang FJ;Tang H
B型肝炎病毒（HBV）rtA 181 T/sW 172 * 突变对病毒复制和致病性的影响是近年来研究的热点。本研究旨在通过动物模型研究乙型肝炎病毒rtA 181 T/sW 172 * 突变株的生物学特性。以pHBV4.1（野生型HBV）为模板构建rtA 181 T/sW 172 * 突变质粒。利用流体动力学技术建立了野生型和突变型HBV复制小鼠模型。分别于注射质粒后1、3、5、7、10、12、15 d检测血清中B肝炎表面抗原（HBsAg）、乙型肝炎B e抗原（HBeAg）、乙型肝炎病毒DNA（HBV DNA）的滴度及肝组织中HBsAg B核心抗原（HBcAg）、HBV DNA复制中间体（HBV DNA RI）和HBV RNA的含量。在野生型HBV复制小鼠模型中，血清HBsAg在第1、3和5天较高，但从第7天开始降低;而在突变型HBV复制小鼠模型中，血清HBsAg始终处于很低的水平。转染后第1天肝组织中检测到野生型HBV的HBVDNA RI。随后在第3天达到峰值，第5天后逐渐下降，第10天几乎检测不到。然而，突变株的HBV DNA RI水平始终较高，持续时间更长，直到第15天。突变组肝组织中HBsAg和HBcAg的表达水平明显升高。在HBV rtA 181 T/sW 172 * 突变的情况下，血清HBsAg分泌受损，而HBV DNA复制和HBsAg/HBcAg表达在肝脏中增加。这些结果表明，该突变可以削弱HBsAg的分泌，并可能导致病毒核心颗粒在肝脏中的积累。
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. 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. 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. 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.