Liu Cong, Liu Lijuan, Wang Xiuling, Liu Youyi, Wang Miao, Zhu Fan
Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan, 430071, People's Republic of China.
Hubei Province Key Laboratory of Allergy and Immunology, Wuhan, 430071, Hubei Province, People's Republic of China.
Virus Genes. 2017 Dec;53(6):797-806. doi: 10.1007/s11262-017-1479-2. Epub 2017 Jun 20.
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 κB (NF-κB) using shRNA targeting NF-κB/p65 or PDTC (an inhibitor of NF-κB) 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-κB in HepG2 cells. This study might provide a new insight in HBV-associated liver diseases including HCC.
位于7号染色体的人类内源性逆转录病毒W家族（HERV-W）包膜（env）在胎盘中高度表达，并在滋养层发育中具有融合活性。已发现HERV-W env在某些癌症和免疫疾病中过表达。病毒反式激活因子可诱导人类细胞系中HERV-W env的过表达。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可增加HERV-W env的启动子活性，并上调人肝癌HepG2细胞中未剪接和剪接的HERV-W env的mRNA水平及其蛋白水平。有趣的是，我们发现使用靶向NF-κB/p65的shRNA或PDTC（一种NF-κB抑制剂）抑制核因子κB（NF-κB）可减弱HBx诱导的HERV-W env的上调。这些结果表明，HBx可能通过NF-κB上调HepG2细胞中HERV-W env的表达。本研究可能为包括肝癌在内的HBV相关肝病提供新的见解。
