Intracellular antibody fragment against hepatitis B virus X protein does not inhibit viral replication.

Intracellular antibody fragment against hepatitis B virus X protein does not inhibit viral replication.
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DOI:
10.3349/ymj.2006.47.5.721
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发表时间:
2006-10-31
影响因子:
2.4
通讯作者:
Park S
Park S
中科院分区:
医学4区
文献类型:
--
作者:
Jin YH;Hong SH;Kim K;Shin HJ;Park S

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B型肝炎病毒的复制受到X蛋白缺陷的抑制。尽管有几种分子阻断了X蛋白的细胞靶点,减少了B型肝炎病毒子代的产生,但X蛋白特异性抑制剂对病毒复制的影响尚未研究。为了特异性地阻断X蛋白,我们采用了使用针对X蛋白的抗体片段H7单链可变区片段(H7scFv)的细胞内表达方法。我们之前证明了H7单链抗体的细胞质表达可以抑制X蛋白诱导的致瘤性和反式激活。本研究通过内源性B病毒聚合酶活性测定和实时荧光定量PCR检测,细胞内H7 scFv表达抑制报告基因的反式激活,但不抑制病毒复制。我们的研究结果表明,细胞内表达抗X蛋白的抗体片段可能不是抑制B型肝炎病毒复制的替代治疗方式。
Replication of the hepatitis B virus is suppressed by deficiency of the X protein. Although several molecules that block cellular targets of X protein reduce the production of hepatitis B virus progeny, the effect of a specific inhibitor of X protein on viral replication has not been investigated. To block X protein specifically, we adopted an intracellular expression approach using H7 single chain variable fragment (H7scFv), an antibody fragment against X protein. We previously demonstrated that cytoplasmic expression of H7scFv inhibits X protein-induced tumorigenicity and transactivation. In this study, intracellular H7scFv expression inhibits reporter gene transactivation but not viral replication determined by endogenous hepatitis B virus polymerase activity assay and real-time PCR. Our findings imply that intracellular expression of antibody fragment against X protein may not be an alternative therapeutic modality for inhibition of hepatitis B virus replication.