EASL2015:锌指抗病毒蛋白AGAINST疗效 乙型肝炎病毒转录和复制的

StephenW

P0533
THE EFFICACY OF ZINC FINGER ANTIVIRAL PROTEIN AGAINST
HEPATITIS B VIRUS TRANSCRIPTION AND REPLICATION IN
TRANSGENIC MOUSE MODEL
E.-Q. Chen1,2, H. Tang1,2, J. Dai1,2, L. Bai1,2. 1Center of Infectious
Diseases, West China Hospital of Sichuan University, 2Division of
Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan
University, Chengdu, China
E-mail: [email protected]
Background and Aims: The zinc finger antiviral protein (ZAP) is
a mammalian host restriction factor, and it could inhibit HBV RNA
synthesis in vitro experiments. However, the role of ZAP against
HBV in vivo environment is unclear. This study aimed to investigate
whether ZAP could act against HBV transcription and replication in
ZAP tansgenic mouse model.
Methods: HBV-replication-competent plasmid pHBV4.1 was
transferred to ZAP transgenic ICR mice via the tail vein, using
a hydrodynamic in vivo transfection procedure. HBV RNA and
HBVDNA replication intermediates in the liver were respectively
analyzed by Northern blotting and Southern blotting. The
expression of hepatitis B surface antigen (HBsAg) and hepatitis B
core antigen (HBcAg) in the liver tissue was detected by
immunohistochemical staining.
Results: As compared to control ICR mouse, the level of HBVRNA
in ZAP transgenic mouse liver tissue was only decreased by 8.4%;
while the level of HBVDNA replication intermediates was decreased
by 82%. In addition, the expression levels of HBsAg and HBcAg in
ZAP transgenic mouse liver were both significantly less than that
of control ICR mouse.
Conclusions: Our findings suggest that ZAP could inhibit HBV
replication in vivo in mice, which offers a new target for anti-HBV
drug development.

StephenW

P0533
锌指抗病毒蛋白AGAINST疗效
乙型肝炎病毒转录和复制的
转基因小鼠模型
E.-Q. Chen1,2，H. Tang1,2，J. Dai1,2，L. Bai1,2。传染性1Center
疾病，西中国四川大学，2区的医院
传染病，生物治疗，四川省国家重点实验室
大学，成都，中国
电子邮件：[email protected]
背景和目的：锌指抗病毒蛋白（ZAP）是
哺乳动物宿主的制约因素，故能抑制HBV RNA
合成的体外实验。然而，ZAP对角色
乙肝病毒的体内环境目前还不清楚。本研究旨在探讨
ZAP是否能起到抗HBV转录和复制的
ZAP tansgenic小鼠模型。
方法：HBV-复制能力的质粒pHBV4.1是
传送经尾静脉给ZAP转基因ICR小鼠，用
液力体内转染过程。 HBV RNA和
在肝脏HBVDNA复制中间体分别
通过Northern杂交和Southern印迹分析。该
乙型肝炎表面抗原（HBsAg）和乙型肝炎的表达
核心抗原（HBcAg的）在肝脏组织中被检测到
免疫组化染色。
结果：相对于对照ICR小鼠，HBVRNA的水平
在ZAP转基因小鼠肝组织仅下降8.4％;
而HBVDNA复制中间体的水平降低
了82％。此外，该表达HBsAg和HBcAg的在水平
ZAP转基因小鼠肝脏均显著小于
控制ICR鼠标。
结论：我们的研究结果表明，ZAP能够抑制HBV
在小鼠体内的复制，它提供了一个新的靶点抗HBV
药物开发。