Intravascular transfer contributes to postprandial increase in numbers of very-low-density hepatitis C virus particles

Felmlee, D. J. et al. (2010) Intravascular transfer contributes to postprandial increase in numbers of very-low-density hepatitis C virus particles. Gastroenterology, 139(5), pp. 1774-1783. (doi:10.1053/j.gastro.2010.07.047) (PMID:20682323)

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Abstract

Background and Aims: The physical association of hepatitis C virus (HCV) particles with lipoproteins in plasma results in distribution of HCV in a broad range of buoyant densities. This association is thought to increase virion infectivity by mediating cell entry via lipoprotein receptors. We sought to determine if factors that affect triglyceride-rich lipoprotein (TRL) metabolism alter the density and dynamics of HCV particles in the plasma of patients with chronic HCV infection. Methods: Fasting patients (n=10) consumed a high-fat milkshake; plasma was collected and fractionated by density gradients. HCV RNA was measured in the very-low–density fraction (VLDF, d<1.025 g/mL) before and at 7 serial time points postprandially. Results: The amount of HCV RNA in the VLDF (HCVVLDF) increased a mean of 26-fold, peaking 180 minutes after the meal (P<0.01). Quantification of HCV RNA throughout the density gradient fractions revealed that HCVVLDF rapidly disappeared, rather than migrating into the adjacent density fraction. Immuno-affinity separation of the VLDF, using antibodies that recognize apoB-100 and not apoB-48 showed that HCVVLDF is composed of chylomicron- and VLDL-associated HCV particles; peaking 120 and 180 minutes after the meal, respectively. Plasma from fasting HCV-infected patients mixed with uninfected plasma increased the quantity of HCVVLDF, compared to that mixed with phosphate-buffered saline, demonstrating extracellular assembly of HCVVLDF. Conclusions: Dietary triglyceride alters the density and dynamics of HCV in plasma. The rapid clearance rate of HCVVLDF indicates that association with TRL is important for HCV infectivity. HCV particles, like exchangeable apolipoproteins, appear to reassociate with TRLs in the vascular compartment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Caslake, Professor Muriel and Packard, Professor Chris and McLauchlan, Professor John
Authors: Felmlee, D. J., Sheridan, D. A., Bridge, S. H., Nielsen, S. U., Milne, R. W., Packard, C. J., Caslake, M. J., McLauchlan, J., Toms, G. L., Neely, R. D. G., and Bassendine, M. F.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Gastroenterology
Publisher:Elsevier B.V.
ISSN:0016-5085
ISSN (Online):1528-0012
Published Online:02 August 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn MclauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH