title: Lipids and HCV.
abstract: Chronic hepatitis C virus (HCV) infection is associated with an increase in hepatic steatosis and a decrease in serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL) and apolipoprotein B (apoB), the main protein constituent of LDL and very low-density lipoprotein (VLDL). These changes are more marked in HCV genotype 3 infection, and effective treatment results in their reversal. Low lipid levels in HCV infection correlate not only with steatosis and more advanced liver fibrosis but also with non-response to interferon-based therapy. The clinical relevance of disrupted lipid metabolism reflects the fact that lipids play a crucial role in the life cycle of hepatitis C virus. HCV assembly and maturation in hepatocytes depend on microsomal triglyceride transfer protein and apoB in a manner that parallels the formation of VLDL. VLDL production from the liver occurs throughout the day with an estimated 10(18) particles produced every 24 h whilst the estimated hepatitis C virion production rate is 10(12) virions per day. HCV particles in the serum exist as a mixture of complete low-density infectious lipo-viral particles (LVP) and a vast excess of apoB-associated empty nucleocapsid-free sub-viral particles that are complexed with anti-HCV envelope antibodies. Apolipoprotein E (apoE) is also involved in HCV particle morphogenesis and is an essential apolipoprotein for HCV infectivity. ApoE is a critical ligand for the receptor-mediated removal of triglyceride rich lipoprotein (TRL) remnants by the liver. The dynamics of apoB-associated lipoproteins, including HCV-LVP, change post-prandially with an increase in large TRL remnants and very low density HCV-LVP which are rapidly cleared by the liver (at least three HCV receptors are cellular receptors for uptake of TRL remnants). In summary, HCV utilises triglyceride-rich lipoprotein pathways within the liver and the circulation to its advantage.
authors.affiliation: Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK. m.bassendine@ncl.ac.uk
authors.forename: M F
authors.initials: MF
authors.lastname: Bassendine
authors.forename: D A
authors.initials: DA
authors.lastname: Sheridan
authors.forename: S H
authors.initials: SH
authors.lastname: Bridge
authors.forename: D J
authors.initials: DJ
authors.lastname: Felmlee
authors.forename: R D G
authors.initials: RD
authors.lastname: Neely
mesh_terms: D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D005234:Fatty Liver / Q000150:complications*; D016174:Hepacivirus / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D015243:Cholesterol, VLDL; D008055:Lipids; D008077:Lipoproteins, LDL; D002784:Cholesterol