Diacylglycerol acyltransferase-1 localizes hepatitis C virus NS5A protein to lipid droplets and enhances NS5A interaction with the viral capsid core.

The triglyceride-synthesizing enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) plays a critical role in hepatitis C virus (HCV) infection by recruiting the HCV capsid protein core onto the surface of cellular lipid droplets (LDs). Here we find a new interaction between the non-structural protein NS5A and DGAT1 and show that the trafficking of NS5A to LDs depends on DGAT1 activity. DGAT1 forms a complex with NS5A and core and facilitates the interaction between both viral proteins.

HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons.

Background & Aims: Polymorphisms in the IL28B gene have been associated with clearance of hepatitis C virus (HCV), indicating a role for type III interferons (IFNs) in HCV infection. Little is known about the function of type III IFNs in intrinsic antiviral innate immunity.

Methods: We used in vivo and in vitro models to characterize the role of the type III IFNs in HCV infection and analyzed gene expression in liver biopsy samples from HCV-infected chimpanzees and patients.