Hepatitis C virus (HCV) is a major cause of liver disease. It affects more than 3 million people in U.S.A. and about 300 million people worldwide. However,  therapeutic options are limited and there are no vaccines for prevention. Viral entry is the first step of infection. A  French team reported on Nature Medicine that HCV infection requires the cooperative interaction of host cell factors epidermal growth factor receptor (EGFR) and ephrin receptor A2 as host cofactors for viral entry. Receptor kinase inhibitors limited infection by most HCV genotypes in vitro and in a human liver chimeric mouse model. Interferon alpha also inhibited viral entry. This study opens the door for the development of new therapeutics and vaccines.