Sex-determining region Y box 4 (SOX4) suppresses Hepatitis B virus replication by inhibiting hepatocyte nuclear factor 4α expression
Sex-determining region Y box 4 (SOX4) suppresses Hepatitis B virus replication by inhibiting hepatocyte nuclear factor 4α expression
复制标题
性别决定区 Y 盒 4 (SOX4) 通过抑制肝细胞核因子 4 α 表达来抑制乙型肝炎病毒复制
DOI：
10.1016/j.antiviral.2020.104745
复制
发表时间：
2020-04-01
影响因子：
7.6
通讯作者：
Lu, Fengmin
中科院分区：
文献类型：
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作者：
Shi, Shu;Liu, Mingchen;Lu, Fengmin
B型肝炎病毒（HBV）感染仍然是世界范围内的一个卫生保健危机，相当数量的慢性B型肝炎患者死于终末期肝病，包括肝硬化和肝细胞癌。先前的研究已经报道了性别决定区Y盒4（SOX 4）通过结合病毒基因组中的AACAAAG基序来促进HBV复制。然而，这样的SOX 4结合位点在大多数HBV基因型株的基因组中未发现。此外，我们发现SOX 4抑制而不是促进大多数HBV毒株的复制。与此一致，当内源性SOX 4被敲低时，HBV复制显著增强。此外，我们证明了SOX 4诱导的HBV复制抑制主要由肝细胞核因子4 α（HNF 4 α）介导。综上所述，我们的研究结果表明，SOX 4通过抑制大多数HBV毒株中HNF 4 α的表达而发挥重要的抗病毒作用。
Hepatitis B virus (HBV) infection is still a health care crisis in the world, and a considerable number of chronic hepatitis B patients die of end-stage liver diseases, including liver cirrhosis and hepatocellular carcinoma. A previous study has reported that sex-determining region Y box 4 (SOX4) promotes HBV replication by binding to the AACAAAG motif in the viral genome. However, such SOX4 binding site was not found in the genome of the majority of HBV genotype strains. Further, we found that SOX4 inhibited rather than promoted the replication of most HBV strains. In line with this, HBV replication was significantly enhanced when the endogenous SOX4 was knocked down. Moreover, we demonstrated that the SOX4-induced suppression of HBV replication was mainly mediated by hepatocyte nuclear factor 4 alpha (HNF4 alpha). Taken together, our findings suggest that SOX4 plays an important antiviral role by inhibiting HNF4 alpha expression in most HBV strains.