Entry cofactors for HCV

Two receptors that act as cellular cofactors for liver cell entry of the hepatitis C virus (HCV) are reported in a study published this week in Nature Medicine. The research suggests that approved inhibitors of these receptors may have utility as antivirals.

HCV causes a chronic liver disease that frequently resists therapy and predisposes infected individuals to hepatocellular carcinoma. More than 170 million individuals worldwide are infected with HCV and new treatment options are needed.

Thomas Baumert and colleagues now report that two receptor tyrosine kinases, epidermal growth factor receptor (EGFR) and ephrin receptor A2 (EphA2), are cellular cofactors involved in entry of HCV into liver cells. Using approved inhibitors of EGFR and EphA2, the authors show that they can impede HCV replication in vitro and in a mouse model of HCV infection. They propose that blocking the receptor tyrosine kinases interferes with fusion of the virus with the cell membrane.