Hepatitis C virus core protein interacts with fibrinogen-β and attenuates cytokine stimulated acute-phase response
✍ Scribed by Malika Ait-Goughoulte; Arup Banerjee; Keith Meyer; Budhaditya Mazumdar; Kousuke Saito; Ratna B. Ray; Ranjit Ray
- Book ID
- 102849562
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 925 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Fibrinogen-beta (FBG-beta), an important acute-phase protein (APP), is generated by the liver as a target for inflammatory mediators. Here we identified FBG-beta as a hepatitis C virus (HCV) core interacting protein by screening a human liver complementary DNA (cDNA) library using mammalian two-hybrid analysis. An association between FBG-beta and HCV core protein was verified by confocal microscopy and coimmunoprecipitation from the transfected human hepatocyte (Huh-7) cell line. HCV core or genomic RNA transfected Huh-7 cells modestly increased FBG-beta protein expression when compared to the basal level in control hepatocytes. Transfection of HCV core or full-length (FL) gene into Huh-7 cells up-regulated basal FBG-beta promoter activity. Exogenous addition of IL-6 stimulates FBG-beta promoter activity in hepatocytes. However, ectopic expression of HCV core or FL in hepatocytes inhibited IL-6-stimulated FBG-beta promoter activation. Inhibition of endogenous FBG-beta expression following introduction of small interfering RNA (siRNA) into cells displayed a gain of function of promoter regulation by HCV core protein. Further studies suggested that HCV core gene expression in stable transfectants of Huh-7 cells resulted in a basal up-regulation of FBG-beta and other APPs. However, treatment with cytokines, interleukin-6 (IL-6), or tumor necrosis factor-alpha repressed FBG-beta and other acute-phase response (APR) genes.
Conclusion:
Our results reveal that the core/fbg-beta interaction may act as a regulatory feedback, allowing repression of il-6-stimulated apr genes. together, these data suggested a network of interactions between hcv core and the hepatic apr genes, and may contribute to impaired innate immunity for viral persistence.