title: Intravascular transfer contributes to postprandial increase in numbers of very-low-density hepatitis C virus particles.
abstract: OBJECTIVE
  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 (HCV(VLDF)) 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 HCV(VLDF) 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 HCV(VLDF) 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 HCV(VLDF), compared with that mixed with phosphate-buffered saline, showing extracellular assembly of HCV(VLDF).
  
  
  CONCLUSIONS
  Dietary triglyceride alters the density and dynamics of HCV in plasma. The rapid clearance rate of HCV(VLDF) 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.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. daniel.felmlee@ncl.ac.uk
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Felmlee
authors.forename: David A
authors.initials: DA
authors.lastname: Sheridan
authors.forename: Simon H
authors.initials: SH
authors.lastname: Bridge
authors.forename: Søren U
authors.initials: SU
authors.lastname: Nielsen
authors.forename: Ross W
authors.initials: RW
authors.lastname: Milne
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Packard
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: John
authors.initials: J
authors.lastname: McLauchlan
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Toms
authors.forename: R Dermot G
authors.initials: RD
authors.lastname: Neely
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Bassendine
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000821:virology; D006801:Humans; D008079:Lipoproteins, VLDL / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load; D014766:Viremia / Q000097:blood* / Q000821:virology; D014771:Virion / Q000378:metabolism*
chemical_list: D008079:Lipoproteins, VLDL; D012367:RNA, Viral