Xu Fengchao, Song Hongxiao, Li Na, Tan Guangyun
Institute of Translational Medicine, Department of Immunology, The First Hospital, Jilin University, Changchun, Jilin, 130061, PR China.
Department of Obstetric, The First Hospital, Jilin University, Changchun, Jilin, 130021, PR China.
Biochem Biophys Res Commun. 2016 Apr 22;473(1):219-223. doi: 10.1016/j.bbrc.2016.03.082. Epub 2016 Mar 19.
Interferon (IFN) is a regularly utilized therapeutic for the treatment of chronic hepatitis B and appears to induce superior HBeAg seroconversion comparing nucleos/tide analogs. However, the mechanisms underlying IFN inhibition of HBV replication, as well as poor responses to IFN are unclear. Apobec3G has been reported to be involved in regulating HBV replication. In this study, we investigated Apobec3G expression and regulatory pathways during HBV infection. We show that over-expression of A3G leads to inhibition of HBV replication. We also show that IFN induces a significant increase in A3G protein expression, which is associated with STAT3 activation. We further show that A3G expression in HBV patients is lower compared to non-infected controls, possibly by HBsAg which inhibits IFN induced A3G up-regulation in a dose dependent manner. This process is likely mediated through inhibition of STAT3-Ser727 phosphorylation. The results presented in this study indicate that STAT3 plays an important role in IFN-induced A3G production, and HBsAg may correlated with poor response to IFN treatment.
干扰素（IFN）是治疗慢性乙型肝炎常用的一种疗法，相较于核苷/核苷酸类似物，它似乎能诱导更高的HBeAg血清学转换。然而，IFN抑制HBV复制的机制以及对IFN反应不佳的原因尚不清楚。据报道，载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（Apobec3G）参与调节HBV复制。在本研究中，我们调查了HBV感染期间Apobec3G的表达及调控途径。我们发现A3G的过表达会导致HBV复制受到抑制。我们还发现IFN会使A3G蛋白表达显著增加，这与信号转导和转录激活因子3（STAT3）的激活有关。我们进一步表明，与未感染的对照组相比，HBV患者体内的A3G表达较低，这可能是由于乙肝表面抗原（HBsAg）以剂量依赖的方式抑制了IFN诱导的A3G上调。这一过程可能是通过抑制STAT3的727位丝氨酸磷酸化介导的。本研究结果表明，STAT3在IFN诱导的A3G产生中起重要作用，且HBsAg可能与IFN治疗反应不佳有关。
