Hepatitis C affects nearly 200 million people worldwide. It results from the failure of the immune system to control the hepatitis C virus (HCV) replication and spread, leading to progressive liver disease that can culminate in fibrosis, cirrhosis and cancer. The inflammatory cells that infiltrate the diseased liver functionally contribute to fibrotic disease and cancer development by the release of potent soluble mediators that regulate cell survival and proliferation, angiogenesis, tissue remodelling, metabolism and genomic integrity. The goal of our work was to study the mechanisms of the initiation of the inflammatory process linked to HCV infection. We have shown that the presence of a single viral protein, namely NS5B, the RNA dependent RNA polymerase, promotes pro-inflammatory signaling. Moreover, inhibition of this pathway in HCV transgenic mice fully protects the animals from HCV-linked liver cancer. Our study contributes to a better understanding of the inflammatory mechanisms linked to HCV infection and thereby to tumorigenesis.
Date:
2013-03-21
Relation:
PLOS Pathogens. 2013 Mar 21;9(3):Article number e1003234.