Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling.
Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling.
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DOI：
10.1371/journal.pone.0156496
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Qin B
中科院分区：
文献类型：
--
作者：
Li L;Lei QS;Zhang SJ;Kong LN;Qin B
泛素特异性蛋白水解酶18(USP18，又称UBP43)具有干扰素刺激基因15(ISG15)依赖和ISG15非依赖的功能。通过沉默USP18在HepG2.2.15细胞中的表达，我们研究了USP18对干扰素-α抗乙肝病毒活性的影响，结果表明，USP18的敲除显著抑制了乙肝病毒的表达，并增加了ISGs的表达。经指示剂量的干扰素-α治疗前后，乙肝病毒表面抗原、e抗原、HBVDNA和细胞内核心抗原水平均显著下降。抑制USP18激活了JAK/STAT信号通路，表现为磷酸化信号转导和转录激活因子1(p-STAT1)的表达增加和延长，同时几个干扰素刺激基因(ISGs)的表达增强。我们的结果表明，USP18通过激活细胞内JAK/STAT信号通路来调节干扰素-α的抗乙肝病毒活性。
Ubiquitin-specific protease 18 (USP18, also known as UBP43) has both interferon stimulated gene 15 (ISG15) dependent and ISG15-independent functions. By silencing the expression of USP18 in HepG2.2.15 cells, we studied the effect of USP18 on the anti-HBV activity of IFN-α and demonstrated that knockdown of USP18 significantly Inhibited the HBV expression and increased the expression of ISGs. Levels of hepatitis B virus surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), HBV DNA and intracellular hepatitis B virus core antigen (HBcAg) were dramatically decreased with or without treatment of indicated dose of IFN-α. Suppression of USP18 activated the JAK/STAT signaling pathway as shown by the increased and prolonged expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) in combination with enhanced expression of several interferon stimulated genes (ISGs). Our results indicated that USP18 modulates the anti-HBV activity of IFN-α via activation of the JAK/STAT signaling pathway in Hepg2.2.15 cells.