Volume 26 Issue 8 - June 6, 2014 PDF
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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
Hung-Yu Sun1, Chun-Chieh Lin2, Jin-Ching Lee3, Shainn-Wei Wang4, Pin-Nan Cheng5, I-Chin Wu5, Ting-Tsung Chang5,6, Ming-Derg Lai2,6, Dar-Bin Shieh6,7, Kung-Chia Young1,2,6,*
1 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
4 Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
5Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
6 Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan
7 Institute of Oral Medicine and Center for Micro-Nano Science and Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
 
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Hepatitis C virus (HCV) infection takes advantage of hepatic lipid/lipoprotein synthesis pathways. Infectious virions associate with intravascular triglyceride-rich lipoproteins, including very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), forming lipo-viro-particles (LVP). Previous studies showed that lipoprotein lipase (LPL), an initial enzyme driving triglyceride hydrolysis of VLDL to finally become LDL, might give hepatocytes the ability to bind HCV but also might suppress productive infections in a cell-based model. This study considers LPL-mediated protection and possible regulation by lipoprotein components (VLDL, LDL and LVP) with samples from normolipidemic blood donors. VLDL and LDL are fractionated by iodixanol density gradient ultracentrifugation, with further immunoglobulin affinity purification of LVP from HCV-infected donor VLDL and LDL fractions. Results show a higher triglyceride/cholesterol ratio of LDL in HCV-infected donors verses healthy donors (0.4 vs. 0.2, P = 0.013, n = 12 each group), 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. Inhibition of LPL activity can be restored by antibodies recognizing apolipoprotein (apo) C-III. Inhibition also correlates with steady and elevated levels of apoC-III in VLDL-VLP and LDL-LVP. Using a cell-based HCV infection system, LPL-mediated inhibition can be reversed by treatment with VLDL and HCV LVPs in an apoC-III dependent manner. Plasma HCV viral loads show significant negative relationship with plasma LPL activity and significant positive relationship with VLDL apoC-III. This study reveals that LPL is an anti-HCV factor.
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