Browse by author
Lookup NU author(s): Professor Margaret Bassendine, Dr David Sheridan, Dr Simon Bridge, Dr Daniel Felmlee, Dr R Neely
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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.
Author(s): Bassendine MF, Sheridan DA, Bridge SH, Felmlee DJ, Neely RDG
Publication type: Review
Publication status: Published
Journal: Seminars in Immunopathology
Year: 2013
Volume: 35
Issue: 1
Pages: 87-100
Print publication date: 31/10/2012
ISSN (print): 1863-2297
ISSN (electronic): 1863-2300
Publisher: SPRINGER HEIDELBERG
URL: http://dx.doi.org/10.1007/s00281-012-0356-2
DOI: 10.1007/s00281-012-0356-2
