The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines
The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines
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DOI：
10.1038/sj.onc.1202643
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发表时间：
1999-05-06
期刊：
影响因子：
8
通讯作者：
Transy, C
中科院分区：
文献类型：
--
作者：
Bergametti, F;Prigent, S;Transy, C
B型肝炎病毒致癌作用与慢性病毒感染的关系尚不明确。事实上，多效性效应已被归因于HBx：除了其间接刺激转录的充分证明的能力之外，该蛋白质已被报道影响细胞生长、信号转导、DNA修复和凋亡。在这项工作中，我们产生了组成型表达野生型或突变型HBx的Chang（CCL-13）衍生的细胞系，作为更接近慢性感染环境的HBx-宿主细胞相互作用的模型，与经典的瞬时表达系统相比，我们证明了HBx对受体细胞中凋亡细胞死亡途径的增强作用。这种作用不太可能依赖于p53活性，因为该蛋白在CCL-13中是功能失活的。此外，抗氧化剂和环孢菌素A未能将凋亡反应降低回正常水平，表明活性氧物质的产生和钙调磷酸酶活化不直接参与HBx的促凋亡作用。相反，我们的数据表明，反式激活和刺激细胞凋亡是紧密相连的HBx活动。最后，反式激活活性蛋白的表达没有导致MAP激酶磷酸化模式的可检测变化，也没有影响宿主细胞修复体外照射质粒DNA的能力。
The role of hepatitis B virus carcinogenesis associated with chronic, viral infection remains ill-defined. Indeed, pleiotropic effects have been ascribed to HBx: in addition to its well-documented ability to indirectly stimulate transcription, the protein has been reported to affect cell growth, signal transduction, DNA repair and apoptosis, In this work, we generated Chang (CCL-13)-derived cell lines constitutively expressing wild type or mutant HBx, as a model of HBx-host cell interaction closer to the chronic infection setting, than the classically used transient expression systems, We document the potentiation by HBx of the apoptotic cell death pathway in the recipient cells. This effect is unlikely to rely on p53 activity since the protein is functionally inactivated in CCL-13, In addition, antioxidants and cyclosporin A failed to reduce the apoptotic response back to the normal level, suggesting that production of reactive oxygen species and calcineurin activation are not directly involved in the proapoptotic effect of HBx. In contrast, our data show that transactivation and stimulation of apoptosis are tightly linked HBx activities. Finally, expression of transactivation-active protein did not result in detectable change in the pattern of MAP kinases phosphorylation nor did it affect the ability of the host cell to repair in vitro irradiated plasmid DNA.