Hepatitis B virus (HBV) induces the expression of interleukin-8 that in turn reduces HBV sensitivity to interferon-alpha

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• 作者：Teresa Pollicino ; Luigi Bellinghieri ; Agnese Restuccia ; Giuseppina Raffa ; Cristina Musolino ; Angela Alibr ; i ; Diana Teti ; Giovanni Raimondo
• 关键词：Hepatitis B virus chronic infection ; Interleukin-8 ; IL-8 promoter ; Transcription factors ; Hepatitis B X viral regulatory protein ; Signal pathways ; Chromatin immunoprecipitation ; Chromatin modifying enzymes ; IL-8 siRNA ; Interferon-alpha
• 刊名：Virology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：444
• 期：1-2
• 页码：317-328
• 全文大小：1867 K

文摘

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-¦Á) 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-¦Á 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-¦Á.