Very low-density lipoprotein/lipo-viro particles reverse lipoprotein lipase-mediated inhibition of hepatitis C virus infection via apolipoprotein C-III
| Autor: | Jin-Ching Lee, Kung Chia Young, Ming Derg Lai, Pin-Nan Cheng, Hung Yu Sun, I-Chin Wu, Shainn Wei Wang, Chun Chieh Lin, Ting-Tsung Chang, Dar-Bin Shieh |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Very low-density lipoprotein Apolipoprotein C Apolipoprotein B Lipolysis Blood Donors Hepacivirus Lipoproteins VLDL Young Adult chemistry.chemical_compound Internal medicine medicine Humans Cells Cultured Triglycerides Intermediate-density lipoprotein Apolipoprotein C-III Lipoprotein lipase Virulence biology Chemistry Cholesterol Virion Gastroenterology nutritional and metabolic diseases Hepatitis C Chronic Viral Load Lipoproteins LDL Lipoprotein Lipase Endocrinology Biochemistry biology.protein Female lipids (amino acids peptides and proteins) Lipoprotein |
| Zdroj: | Gut. 62:1193-1203 |
| ISSN: | 1468-3288 0017-5749 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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