P50 Apolipoprotein E and low-density, apolipoprotein B associated lipoviral particles in chronic hepatitis C infection: evidence for genotype-specific modulation of lipid pathways

Introduction Hepatitis C virus (HCV) co-opts the VLDL assembly, maturation, degradation, and secretory machinery of hepatocytes. Infectious low density particles have been termed lipoviral particles (LVP). LVPs in vivo are triglyceride (TG) rich and contain at least viral RNA, HCV core protein and the VLDL components apolipoprotein B (apoB) and apoE. ApoE is a constituent of infectious HCV particles produced in cell culture, and production of infectious particles is dramatically impaired from cells in which apoE expression has been genetically silenced. Aim To examine the relationship between LVP and apoE in vivo. Method Fasting plasma samples were obtained from 39 chronic HCV genotype (G) three patients and 51 HCV G1 patients. LVP were measured using iodixanol density gradient ultracentrifugation as recently described.1 ApoE levels were determined by an automated immunonephlometric method. Demographic data were recorded and liver biochemical tests, lipid profiles and HOMA-IR were measured in all patients. Results The mean LVP in HCV G3 was 5.2 log10 IU/ml with a mean LVP ratio of 0.286, but showed wide variation (0.03–0.96). This was not significantly different to LVP variation in HCV G1 we have previously reported.1 In HCV G1 we found a strong positive correlation of LVP HCV RNA with apoE levels (r=0.488, p=0.001) and also with LVP ratio (r=0.428, p=0.001). In contrast in HCV G3 we found a significant negative correlation of LVP HCV RNA with apoE levels (r=−0.428, p=0.013), suggesting different utilisation of lipoprotein pathways. We also found a negative correlation of LVP in HCV G3 with HDL cholesterol (r= −0.468, p=0.003) and its structural lipoprotein apoA1 (r= −0.479, p=0.002) whereas we have reported no correlation of LVP in cHCVG1 with HDL or apoA1.1 Furthermore in HCV G3 we found low TG levels compared to G1 (1.00±0.71 vs 1.35±0.76) and no correlation of LVP with TG or HOMA-IR, again contrasting to G1 infection1. Conclusion This study suggests that while serum apoE quantity is a positive determinant for LVP quantity in HCV G1 infection, it is a negative determinant in HCV G3 infection. Furthermore, LVP quantity in HCV G3 is largely based on the paucity of HDL quantity and their components, rather than the parameters associated with TRL levels as in HCV G1. These differences highlight that interaction with host lipoprotein metabolism is important for HCV infection in different genotypes, but in genotype specific ways.