Very low-density lipoprotein/lipo-viro particles reverse lipoprotein lipase-mediated inhibition of hepatitis C virus infection via apolipoprotein C-III.
OBJECTIVE
Circulating hepatitis C virus (HCV) virions are associated with triglyceride-rich lipoproteins, including very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), designated as lipo-viro-particles (LVPs). Previous studies showed that lipoprotein lipase (LPL), a key enzyme for hydrolysing the triglyceride in VLDL to finally become LDL, may suppress HCV infection. This investigation considers the regulation of LPL by lipoproteins and LVPs, and their roles in the LPL-mediated anti-HCV function.


METHODS
The lipoproteins were fractionated from normolipidemic blood samples using iodixanol gradients. Subsequent immunoglobulin-affinity purification from the canonical VLDL and LDL yielded the corresponding VLDL-LVP and LDL-LVP. Apolipoprotein (apo) Cs, LPL activity and HCV infection were quantified.


RESULTS
A higher triglyceride/cholesterol ratio of LDL was found more in HCV-infected donors than in healthy volunteers, and the triglyceride/cholesterol ratio of LDL-LVP was much increased, suggesting that the LPL hydrolysis of triglyceride may be impaired. VLDL, VLDL-LVP, LDL-LVP, but not LDL, suppressed LPL lipolytic activity, which was restored by antibodies that recognised apoC-III/-IV and correlated with the steadily abundant apoC-III/-IV quantities in those particles. In a cell-based system, treatment with VLDL and LVPs reversed the LPL-mediated inhibition of HCV infection in apoC-III/-IV-dependent manners. A multivariate logistic regression revealed that plasma HCV viral loads correlated negatively with LPL lipolytic activity, but positively with the apoC-III content of VLDL. Additionally, apoC-III in VLDL was associated with a higher proportion of HCV-RNA than was IgG.


CONCLUSIONS
This study reveals that LPL is an anti-HCV factor, and that apoC-III in VLDL and LVPs reduces the LPL-mediated inhibition of HCV infection.
Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Hung-Yu
HY
Sun
Chun-Chieh
CC
Lin
Jin-Ching
JC
Lee
Shainn-Wei
SW
Wang
Pin-Nan
PN
Cheng
I-Chin
IC
Wu
Ting-Tsung
TT
Chang
Ming-Derg
MD
Lai
Dar-Bin
DB
Shieh
Kung-Chia
KC
Young
D000328:Adult; D053305:Apolipoprotein C-III / Q000502:physiology*; D001782:Blood Donors; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000821:virology; D006801:Humans; D008066:Lipolysis / Q000502:physiology; D008071:Lipoprotein Lipase / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood / Q000502:physiology*; D008297:Male; D014280:Triglycerides / Q000097:blood; D019562:Viral Load; D014771:Virion / Q000378:metabolism; D014774:Virulence / Q000502:physiology; D055815:Young Adult
D053305:Apolipoprotein C-III; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase