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Intravascular Transfer Contributes to Postprandial Increase in Numbers of Very-Low-Density Hepatitis C Virus Particles

Lookup NU author(s): Dr Daniel Felmlee, Dr David Sheridan, Dr Simon Bridge, Dr Soren Nielsen, Professor Geoff Toms, Dr R Neely, Professor Margaret Bassendine

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Abstract

BACKGROUND & 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 < .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 apolipoprotein B-100 and not apolipoprotein B-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 with that mixed with phosphate-buffered saline, showing 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, such as exchangeable apolipoproteins, appear to reassociate with TRLs in the vascular compartment.


Publication metadata

Author(s): Felmlee DJ, Sheridan DA, Bridge SH, Nielsen SU, Milne RW, Packard CJ, Caslake MJ, McLauchlan J, Toms GL, Neely RDG, Bassendine MF

Publication type: Article

Publication status: Published

Journal: Gastroenterology

Year: 2010

Volume: 139

Issue: 5

Pages: 1774-1783

Print publication date: 02/08/2010

ISSN (print): 0016-5085

ISSN (electronic): 1528-0012

Publisher: WB Saunders Co.

URL: http://dx.doi.org/10.1053/j.gastro.2010.07.047

DOI: 10.1053/j.gastro.2010.07.047


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