Massachusetts General Hospital, Harvard Medical School, GI Unit, Boston, Massachusetts.
The hepatitis C virus (HCV) requires elements of host lipid metabolism for every step in the viral life cycle. Clinically, it has long been observed that patients with chronic hepatitis C have lower nonhigh-density lipoprotein cholesterol, and these levels rise after successful treatment. The HCV itself circulates as a highly lipidated lipoviral particle, which closely resembles very low-density lipoprotein (VLDL). Several required coentry factors for the virus to gain access to the hepatocytes have been described, and several, including SRB1, LDL-R, and the NPC1L1 receptors, are important receptors for lipoprotein and cholesterol uptake. Inside the cell, the virus induces lipogenesis, and specifically induces the master regulator sterol response element binding protein. Viral replication then requires the concerted efforts of viral proteins combined with several host factors involved in cholesterol synthesis. The virus is then packaged alongside the cellular machinery for VLDL production. The complex interplay highlights pathways of hepatic steatosis and unveils drug targets for the treatment of HCV.