HBV X Protein induces overexpression of HERV-W env through NF-κB in HepG2 cells
HBV X Protein induces overexpression of HERV-W env through NF-κB in HepG2 cells
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HBV X 蛋白通过 NF-κB 在 HepG2 细胞中诱导 HERV-W env 过度表达。
DOI：
10.1007/s11262-017-1479-2
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发表时间：
2017-12-01
期刊：
影响因子：
1.6
通讯作者：
Zhu, Fan
中科院分区：
文献类型：
--
作者：
Liu, Cong;Liu, Lijuan;Zhu, Fan
位于 7 号染色体的人内源性逆转录病毒 W 家族 (HERV-W) 包膜 (env) 在胎盘中高表达，并在滋养层发育中具有融合活性。研究发现，HERV-W env 在某些癌症和免疫疾病中过度表达。病毒反式激活剂可以诱导人类细胞系中 HERV-W env 的过度表达。乙型肝炎病毒X蛋白（HBx）被认为是一种多功能致癌蛋白。在此，我们报道HBx可以增加人肝癌HepG2细胞中HERV-W env的启动子活性，并上调非剪接和剪接的HERV-W env及其蛋白质的mRNA水平。有趣的是，我们发现使用靶向 NF-kappa B/p65 的 shRNA 或 PDTC（NF-kappa B 抑制剂）抑制核因子 kappa B (NF-kappa B) 可以减弱 HBx 诱导的 HERV-W env 上调。这些表明HBx可能通过NF-kappa B上调HepG2细胞中HERV-W env的表达。这项研究可能为包括 HCC 在内的 HBV 相关肝病提供新的见解。
Human endogenous retrovirus W family (HERV-W) envelope (env) at chromosome 7 is highly expressed in the placenta and possesses fusogenic activity in trophoblast development. HERV-W env has been found to be overexpressed in some cancers and immune diseases. Viral transactivators can induce the overexpression of HERV-W env in human cell lines. Hepatitis B virus X protein (HBx) is believed to be a multifunctional oncogenic protein. Here, we reported that HBx could increase the promoter activity of HERV-W env and upregulate the mRNA levels of non-spliced and spliced HERV-W env and also its protein in human hepatoma HepG2 cells. Interestingly, we found that the inhibition of nuclear factor kappa B (NF-kappa B) using shRNA targeting NF-kappa B/p65 or PDTC (an inhibitor of NF-kappa B) could attenuate the upregulation of HERV-W env induced by HBx. These suggested that HBx might upregulate the expression of HERV-W env through NF-kappa B in HepG2 cells. This study might provide a new insight in HBV-associated liver diseases including HCC.