Hepatitis C virus (HCV) is a small, enveloped virus comprising an RNA genome encased in a protein capsid and surrounded by a lipid bilayer containing two glycoproteins. Acute infection can cause hepatitis but the virus usually persists as a chronic infection of the liver where it can cause inflammation and, eventually, hepatocellular carcinoma. How HCV subverts hepatocytes to turn them into virus-producing factories, has remained unclear.
In a paper publishing in the Open Access journal PLOS Biology on 31st March, a research team based in Lyon (France) finds a small secreted protein, Netrin-1, closely implicated in the lifecycle of this virus. Romain Parent and his collaborators report that HCV enhances expression of Netrin-1 in hepatocytes and, in turn, Netrin-1 increases both the amount of the viral RNA genome and the infectivity of the virus particles produced. What’s more, the authors present evidence that Netrin-1 also promotes viral uptake into uninfected cells, perhaps by blocking internalisation of the epidermal growth factor receptor (EGFR) and so increasing the amount of this cofactor for viral uptake on the cell surface.
HCV replicates mainly in the hepatocytes of the liver. It enters these cells by complex interactions with several cell surface proteins and, once inside, replicates on intracellular membranes, in particular those of the endoplasmic reticulum (ER). These authors were drawn to study the possible role of Netrin-1 in HCV infection because of previous studies showing its involvement in several cancer types as well as in inflammatory diseases associated with cancer.