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Very low-density lipoprotein/lipo-viro particles reverse lipoprotein lipase-mediated inhibition of hepatitis C virus infection via apolipoprotein C-III
  1. Hung-Yu Sun1,
  2. Chun-Chieh Lin2,
  3. Jin-Ching Lee3,
  4. Shainn-Wei Wang4,
  5. Pin-Nan Cheng5,
  6. I-Chin Wu5,
  7. Ting-Tsung Chang5,6,
  8. Ming-Derg Lai2,6,
  9. Dar-Bin Shieh6,7,
  10. Kung-Chia Young1,2,6
  1. 1Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  2. 2Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  3. 3Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
  4. 4Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  5. 5Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  6. 6Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  7. 7Institute of Oral Medicine and Center for Micro-Nano Science and Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  1. Correspondence to Dr Kung-Chia Young, No. 1, University Rd., Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; t7908077{at}mail.ncku.edu.tw

Abstract

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.

Design 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.

Conclusion 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.

  • Apolipoprotein C
  • hepatitis C virus
  • lipoprotein
  • lipo-viro-particle
  • lipoprotein lipase
  • viral load

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Footnotes

  • Funding This study was supported by the National Science Council of Taiwan under Grant numbers NSC 96-2320-B-006-005, NSC 96-2628-B-006-007-MY3 and 99-2320-B-006-015-MY3.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by National Cheng Kung University Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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