Lipids and HCV

Bassendine, Margaret, Sheridan, David, Bridge, Simon, Felmlee, Daniel and Neely, Robert Dermot (2013) Lipids and HCV. Seminars in Immunopathology, 35 (1). pp. 87-100. ISSN 1863-2297

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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 1018 particles produced every 24 h whilst the estimated hepatitis C virion production rate is 1012 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.

Item Type: Article
Uncontrolled Keywords: Lipid droplets, lipoprotein, VLDL, triglycerides, LDL receptor, lipo-viral particles
Subjects: A100 Pre-clinical Medicine
C900 Others in Biological Sciences
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Ellen Cole
Date Deposited: 13 Dec 2012 15:57
Last Modified: 12 Oct 2019 18:28

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