Host Kinases Linked to HCV Infection


geodesic domeGlobally, around 200 million people are infected with Hepatitis C virus (HCV). Infection generally leads to chronic liver disease, albeit over a period of decades, which can lead to cirrhosis, hepatocellular carcinoma and liver failure. Current treatment, a combination of pegylated interferon-α and ribavirin, is only effective in 50-85% of patients, dependent on viral genotype. Not surprisingly, much effort is being expended to identify new therapeutic interventions.

Study of the viral lifecycle has been difficult in the past since serum-derived HCV (sHCV) replicates poorly in primary human hepatocytes and hepatoma cells in vitro. Surrogate systems have been developed, however, that have enabled reproduction of all steps of the HCV replication cycle, including cell entry (recently reviewed).

Viral cell entry is still incompletely understood, but a new study from researchers at the University of Rennes 1 has identified host kinases involved in HCV infectivity. Using a small-interfering RNA (siRNA) library, the scientists have shown that knock-down of phosphatidylinositol 4-kinase type III-α (PI4KIIIα) prevents infection by either HCV pseudoparticles (HCVpp) or by cell-culture grown JFH-1-based HCV (HCVcc). A second PI4K-family member, PI4KIIIβ, also influenced cellular susceptibility to HCVpp infection and the ability of the cells to sustain HCV replication. These kinases may therefore represent new targets for HCV therapeutics.

The study is published in the FASEB Journal.

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