HCV Core Protein Linked to Immune Evasion in Liver Cells

The core protein of the hepatitis C virus (HCV) has been implicated in the development of hepatocellular carcinoma (HCC).

As reported in the October 2006 issue of Virology, researchers from the University of California at Davis conducted a laboratory study to investigate the early influence of the core protein on hepatocyte (liver cell) gene expression, and to identify molecular processes modulated by the protein.

Because it is difficult to culture and maintain HCV in the laboratory, the researchers used a HepG2 human hepatocyte cell line with inducible expression of HCV-1b core protein.

Results

The investigators observed a significant change in the expression of 407 genes, including genes regulating apoptosis (programmed cell death), immune response, and progression through the cell cycle.

Some of these genes were previously identified as tumor markers.

Decreased expression of chemo-attractants such as tumor necrosis factor (TNF) SF10, CCL20 (also known as liver and activation-regulated chemokine), and osteopontin was observed, suggesting that expression of the HCV core protein could lead to suppression of the inflammatory response and mobilization of macrophages and neutrophils to the site of HCV infection.

Increased expression of anti-apoptosis factors including PAK2, API5, BH1, Tax1BP1, DAXX, and TNF AIP3/A20 was also observed.

Some of these genes were linked with regulation of NF-kappa-B (NFKB) activation, suggesting that alteration of their expression by the HCV core protein might lead to the suppression of NFKB activation of inflammatory responses.

Conclusion

In conclusion, the authors wrote, these data suggested that HCV core protein expression may contribute to viral persistence by protecting infected hepatocytes from cell death by suppressing apoptosis and inflammatory response to HCV infection.

Reference
H Nguyen, S Sankaran, S Dandekar. Hepatitis C virus core protein induces expression of genes regulating immune evasion and anti-apoptosis in hepatocytes. Virology 354(1): 58-68. October 2006.