Transforming growth factor-β suppresses hepatitis B virus replication primarily through transcriptional inhibition of pregenomic RNA
Transforming growth factor-β suppresses hepatitis B virus replication primarily through transcriptional inhibition of pregenomic RNA
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DOI：
10.1002/hep.21726
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发表时间：
2007-09-01
期刊：
影响因子：
13.5
通讯作者：
Chang, Chungming
中科院分区：
文献类型：
--
作者：
Chou, Yu-Chi;Chen, Mong-Liang;Chang, Chungming
转化生长因子- β (tgf - β 1)是一种多效性细胞因子，在调节细胞功能和免疫应答中起关键作用。在这项研究中，我们发现tgf - β 1能够有效抑制乙型肝炎病毒（HBV）的复制。在tgf - β 1存在的情况下，活跃分裂细胞和融合细胞中病毒复制中间体的水平都显著降低。同时，tgf - β 1处理显著降低了病毒转录物、核心蛋白和核衣壳的水平。有趣的是，与pre-C mRNA相比，tgf - β 1的抑制活性与前基因组RNA水平的优先降低有关。进一步分析表明，tgf - β 1可能主要通过转录调控而非转录后修饰降低HBV核心蛋白的表达来发挥抗病毒作用。结论：tgf - β 1可能在HBV感染中发挥双重作用，一方面抑制病毒感染的免疫应答，另一方面直接抑制病毒复制，从而使慢性肝炎患者的肝损害最小化。
Transforming growth factor-betal (TGF-beta 1) is a pleiotropic cytokine with pivotal roles in the regulation of cellular functions and immune responses. In this study, we found that TGF-beta 1 was able to effectively suppress hepatitis B virus (HBV) replication. In the presence of TGF-beta 1, the level of viral replicative intermediates was dramatically decreased, both in actively dividing cells and in confluent cells. At the same time, the levels of viral transcripts, core protein, and nucleocapsid were significantly diminished by TGF-beta 1 treatment. Interestingly, the inhibitory activity of TGF-beta 1 was associated with preferential reduction of the level of pregenomic RNA compared with pre-C mRNA. Further analysis indicated that TGF-beta 1 might exert its antiviral effect primarily through reducing expression of the HBV core protein by transcriptional regulation instead of posttranscriptional modification. Conclusion: TGF-beta 1 may play a dual role in HBV infection, in the suppression of immune responses against viral infection and in the direct inhibition of viral replication, resulting in minimization of liver damage in patients with chronic hepatitis.