TRIM28通过抑制干扰素JAK-STAT信号通路促进乙肝病毒复制机制

TRIM28 Promotes HBV Replication by Inhibition of the Activation of JAK/STAT Signaling Pathway by IFN-α

对TRIM28和乙肝病毒(HBV)持续感染之间的联系进行了初步探讨.研究发现,在支持HBV感染和复制的人肝细胞HLCZ01中,过表达TRIM28抑制α-干扰素(IFN-α)的抗HBV作用,且降低了干扰素诱导基因(ISGs)的表达水平;而在细胞内沉默TRIM28则增强IFN-α的抗HBV作用,并且上调多种ISGs的表达.在HBV复制的HepG2.2.15中,也得到了类似的实验结果.在HLCZ01细胞内,TRIM28仅抑制IFN诱导的ISGs产生,但不影响IFN上游信号分子STAT1与STAT2的磷酸化水平.TRIM28的表达水平在乙肝病人肝组织中显著高于正常人肝组织,同时HBV感染HLCZ01细胞后,使得细胞内TRIM28表达水平上调.研究结果表明,TRIM28通过抑制JAK-STAT信号通路来减弱IFN-α的抗HBV作用,并且HBV可能通过上调TRIM28的表达来实现其免疫逃逸,为研究HBV的慢性感染机制提供了新思路.

This study focused on exploring the association between TRIM28and chronic HBV infection.In HLCZ01cells,ectopic expression of TRIM28attenuated the antiviral activity against HBV adopted by IFN-αtreatment.In contrast,the replication of HBV was augmented in TRIM28-silencing cells.Besides,TRIM28exhibits the same effect on HBV in HepG2.2.15cells.In human hepatocytes,TRIM28can suppress Type I interferon-induced ISGs production,but show no effect on the activation of STAT1and STAT2.Importantly,TRIM28expression in liver tissue from HBV-infected patients is higher than that in normal liver tissue and HBV infection induces the TRIM28upregulation in HLCZ01cells.Briefly,our data shows that TRIM28weakens the antiviral activity of IFN-αagainst HBV by inhibiting the signal transduction in JAK/STAT pathway,which might be a trick played by HBV for successful immune evasion.Our finding provides a new insight into chronic HBV infection mechanism.