Department of Pediatric, Gynecologic, Microbiological, and Biomedical Sciences, University of Messina, Messina, Italy.
Virology. 2013 Sep;444(1-2):317-28. doi: 10.1016/j.virol.2013.06.028. Epub 2013 Jul 23.
High levels of serum interleukin-8 (IL-8) have been detected in chronic hepatitis B (CHB) patients during episodes of hepatitis flares. We investigated whether hepatitis B virus (HBV) may directly induce IL-8 production and whether IL-8 may antagonize interferon-alpha (IFN-α) antiviral activity against HBV. We showed that CHB patients had significantly higher IL-8 levels both in serum and in liver tissue than controls. In HBV-replicating HepG2 cells, IL-8 transcription was significantly activated. AP-1, C/EBP and NF-kB transcription factors were concurrently necessary for maximum IL-8 induction. Moreover, HBx viral protein was recruited onto the IL-8 promoter and this was paralleled by IL8-bound histone hyperacetylation and by active recruitment of transcriptional coactivators. Inhibition of IL-8 increases the antiviral activity of IFN-α against HBV. Our results indicate that HBV activates IL-8 gene expression by targeting the epigenetic regulation of the IL-8 promoter and that IL-8 may contribute to reduce HBV sensitivity to IFN-α.
在慢性乙型肝炎（CHB）患者肝炎发作期间，血清白细胞介素-8（IL-8）水平升高。我们研究了乙型肝炎病毒（HBV）是否可以直接诱导 IL-8 的产生，以及 IL-8 是否可以拮抗干扰素-α（IFN-α）对 HBV 的抗病毒活性。结果表明，CHB 患者的血清和肝组织中 IL-8 水平明显高于对照组。HBV 复制的 HepG2 细胞中，IL-8 转录明显被激活。AP-1、C/EBP 和 NF-κB 转录因子同时对于最大程度地诱导 IL-8 是必需的。此外，HBx 病毒蛋白被募集到 IL-8 启动子上，这与 IL8 结合的组蛋白乙酰化增加以及转录共激活因子的活性募集平行。抑制 IL-8 可增加 IFN-α 对 HBV 的抗病毒活性。我们的结果表明，HBV 通过靶向 IL-8 启动子的表观遗传调控来激活 IL-8 基因表达，并且 IL-8 可能有助于降低 HBV 对 IFN-α 的敏感性。
