Complementing these well-characterized clinical observations, recent molecular studies of HCV–host interactions in state-of-the-art cell culture and animal models have convincingly demonstrated that HCV exploits lipid biosynthesis pathways for its viral life cycle JQ1 price (for review, see Georgel et al.2 and Jones and McLauchlan3). Following

HCV entry and replication, the viral life cycle is completed by viral assembly and egress of infectious viral particles.2 Virus assembly and production require key factors of lipid biosynthesis, and circulating virions are associated with lipid proteins (for review, see Negro1 and Jones and McLauchlan3). A unique feature of HCV assembly in the infected hepatocyte is the interaction of the viral capsid protein core with a lipid-storing cell organelle—the lipid droplet (LDs).3, 4 LDs consist of neutral lipids, predominantly triacylglycerols (TGs) or cholesteryl

esters, that are surrounded by a monolayer of phospholipids and associated proteins.5 The neutral lipids that are stored in LDs are used for metabolism, membrane synthesis (phospholipids and cholesterol), and steroid synthesis. In addition, LDs have a crucial role in storing cholesterol in the form of LY294002 cell line cholesteryl esters. This function is part of the complex homeostatic mechanisms that are involved in regulating the level of intracellular free cholesterol. Interestingly, association of the viral core with LDs has been shown to be essential for infectious HCV production (for review, see Jones and McLauchlan3). It is assumed that nascent viral genomes are transported from the replication sites to core-associated LDs via the recruitment of nonstructural proteins selleck screening library NS3 and NS5A on the LD surface.4, 6, 7 Subsequently, following formation of the assembly complex and envelopment, maturation and secretion pathway (for review, see Jones and McLauchlan3), including

apolipoproteins as essential host factors for virus production.8 A recent report in Nature Medicine produced by Melanie Ott’s laboratory at the Gladstone Institute in San Francisco, CA, provides another important link between the HCV life cycle and lipid metabolism: In this study, the authors elegantly demonstrate that HCV particle formation requires a novel cellular factor: diacylglycerol acyltransferase-1 (DGAT1).9 DGAT1 is an enzyme required for TG biosynthesis specifically present in hepatocytes, adipocytes and enterocytes. The final step of TG biosynthesis is the covalent association between a fatty acyl-coenzyme A and diacylglycerol to form a TG. This reaction is catalyzed by DGAT1 or DGAT2.10 TGs are synthesized in the endoplasmic reticulum (ER), accumulate in the leaflet lipid bilayer, and are channeled into the cytosol.