近日，中科院微生物研究所孟颂东课题组发现了干扰素抗乙肝病毒的新作用机制。相关研究成果日前发表于《病毒学杂志》。
干扰素作用过程
据了解，使用干扰素（IFN-α）和抗病毒药物是目前治疗慢性乙肝病毒感染的基本手段。干扰素治疗是目前药物治疗后持续应答率最高的治疗方法。少数患者在治疗后，可伴随表面抗原转阴，达到治疗慢性乙肝的终极目标。但干扰素对不同乙肝患者的疗效差异很大，学界对此作用机制并不完全清楚。
该课题组郝军莉等人在前期工作的基础上，发现干扰素可显著下调肝细胞中丰度最高且特异表达的小RNAmiR-122的水平。进一步研究发现，干扰素不是主要在转录水平调节miR-122，而是上调至少一种干扰素活化基因（ISG）NT5C3的表达。
同时，NT5C3 mRNA的3"-UTR包含有miR-122的作用靶点，大量表达的NT5C3 mRNA以“海绵”吸附方式抑制并下调miR-122。由于miR-122可显著抑制乙肝病毒的表达与复制，因此miR-122的下调对干扰素抗病毒的效果产生了极大的负面影响。
业内专家认为，该成果部分解释了干扰素对乙肝疗效差异大的原因，同时，该研究也为增强干扰素的抗病毒疗效提供了依据。
IFN-α-induced miR-122 inhibition negatively affects the anti-HBV efficiency of IFN-α
Junli Hao, Wensong Jin, Xinghui Li, Saifeng Wang, Xiaojun Zhang, Hongxia Fan, Changfei Li, Lizhao Chen, Bin Gao, Guangze Liu and Songdong Meng
Interferon (IFN)-α based therapy can effectively treat chronic hepatitis B virus (HBV) infection which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced marked decrease of miR-122 expression in hepatocytes. We next showed that IFN-α-induced miR-122 down-regulation was only partly due to transcriptional suppression. One IFN-stimulated gene (ISG) NT5C3 which was identified as a miR-122 target, efficiently inhibited miR-122 by binding and sequestering miR-122 with its mRNA 3’ -UTR, indicating that ISG is involved in IFN-α-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-α on miR-122 was completely abolished by blocking IFN-α-induced up-regulation of NT5C3 mRNA expression by RNAi. Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-α-mediated HBV inhibitory effects could be significantly enhanced when blocking IFN-α-induced down-regulation of miR-122. We therefore conclude that IFN-α-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insight for better understanding of the anti-viral mechanism of IFN-α and raise further potential interest in enhancing its anti-HBV efficacy.
文献连接：IFN-α-induced miR-122 inhibition negatively affects the anti-HBV efficiency of IFN-α
