HBsAg blocks TYPE I IFN induced up -regulation of A3G through inhibition of STAT3
HBsAg blocks TYPE I IFN induced up -regulation of A3G through inhibition of STAT3
复制标题
HBsAg 通过抑制 STAT3 阻断 I 型 IFN 诱导的 A3G 上调
DOI：
10.1016/j.bbrc.2016.03.082
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发表时间：
2016-04-22
影响因子：
3.1
通讯作者：
Tan, Guangyun
中科院分区：
文献类型：
--
作者：
Xu, Fengchao;Song, Hongxiao;Tan, Guangyun
干扰素（IFN）是治疗慢性B型肝炎的常用治疗剂，与核苷类似物相比，其似乎诱导上级HBeAg血清转换。然而，IFN抑制HBV复制的机制以及对IFN的不良反应尚不清楚。据报道，Apobec 3G参与调节HBV复制。在这项研究中，我们研究了Apobec 3G在HBV感染过程中的表达和调控途径。我们发现A3 G的过度表达导致HBV复制的抑制。我们还表明，IFN诱导A3 G蛋白表达的显着增加，这是与STAT 3激活。我们进一步表明，与未感染的对照相比，HBV患者中的A3 G表达较低，这可能是由于HBsAg以剂量依赖性方式抑制IFN诱导的A3 G上调。该过程可能通过抑制STAT 3-Ser 727磷酸化来介导。本研究的结果提示STAT 3在IFN诱导的A3 G产生中起重要作用，HBsAg可能与IFN治疗的不良反应有关。(C)2016 Elsevier Inc. All rights reserved.
Interferon (IFN) is a regularly utilized therapeutic for the treatment of chronic hepatitis B and appears to induce superior HBeAg seroconversion comparing nucleositide 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. (C) 2016 Elsevier Inc. All rights reserved.