title: High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients.
abstract: Hepatitis C virus (HCV) particles associate viral and lipoprotein moieties to form hybrid lipoviral particles (LVPs). Cell culture-produced HCV (HCVcc) and ex vivo-characterized LVPs primarily differ by their apolipoprotein (apo) B content, which is low for HCVcc, but high for LVPs. Recombinant nucleocapsid-free subviral LVPs are assembled and secreted by apoB-producing cell lines. To determine whether such subviral particles circulate in HCV-infected individuals, LVPs complexed with immunoglobulin were precipitated with protein A from low-density plasma fractions of 36 hepatitis C patients, and their lipid content, apolipoprotein profile, and viral composition were determined. HCV RNA in LVPs was quantified and molar ratios of apoB and HCV genome copy number were calculated. LVPs lipidome from four patients was determined via electrospray ionization/tandem mass spectrometry. Protein A-purified LVPs contained at least the envelope glycoprotein E2 and E2-specific antibodies. LVPs were present in every patient and were characterized by high lipid content, presence of apolipoproteins characteristic of triglyceride-rich lipoproteins (TRLs), HCV RNA, and viral glycoprotein. Importantly, save for four patients, LVPs fractions contained large amounts of apoB, with on average more than 1 × 10(6) apoB molecules per HCV RNA genome. Because there is one apoB molecule per TRL, this ratio suggested that most LVPs are nucleocapsid-free, envelope glycoprotein-containing subviral particles. LVPs and TRLs had similar composition of triacylglycerol and phospholipid classes.
  
  
  CONCLUSIONS
  LVPs are a mixed population of particles, comprising predominantly subviral particles that represent a distinct class of modified lipoproteins within the TRL family.
authors.affiliation: Université de Lyon, France; INSERM U851, Lyon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Scholtes
authors.forename: Christophe
authors.initials: C
authors.lastname: Ramière
authors.forename: Dominique
authors.initials: D
authors.lastname: Rainteau
authors.forename: Laure
authors.initials: L
authors.lastname: Perrin-Cocon
authors.forename: Claude
authors.initials: C
authors.lastname: Wolf
authors.forename: Lydie
authors.initials: L
authors.lastname: Humbert
authors.forename: Martine
authors.initials: M
authors.lastname: Carreras
authors.forename: Aurélie
authors.initials: A
authors.lastname: Guironnet-Paquet
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.forename: Patrice
authors.initials: P
authors.lastname: André
authors.forename: Olivier
authors.initials: O
authors.lastname: Diaz
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000378:metabolism*; D015153:Blotting, Western; D015331:Cohort Studies; D005260:Female; D016174:Hepacivirus / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053419:Lipoproteins, IDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019590:Nucleocapsid Proteins / Q000032:analysis / Q000378:metabolism*; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D014759:Viral Envelope Proteins / Q000378:metabolism; D019562:Viral Load
chemical_list: D001055:Apolipoproteins B; D008075:Lipoproteins, HDL; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus