High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients.
Résumé
Hepatitis C virus (HCV) particles associate viral and lipoprotein moieties to form hybrid lipo-viral-particles (LVP). Cell culture produced HCV (HCVcc) and ex vivo characterized LVP primarily differ by their apolipoprotein B (apoB) content, which is low for HCVcc, but high for LVP. Recombinant nucleocapsid-free subviral LVP are assembled and secreted by apoB producing cell lines. To determine whether such subviral particles circulate in HCV-infected individuals. LVP 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 was determined. HCV RNA in LVP was quantified and molar ratios of apoB and HCV genome copy number were calculated. LVP lipidome from four patients was determined by electrospray ionization tandem mass spectrometry. Protein A purified LVP contained at least the envelope glycoprotein E2 and E2-specific antibodies. LVP were present in every patient and were characterized by high lipid content, presence of apolipoproteins characteristic for triglyceride rich lipoproteins (TRL), HCV RNA and viral glycoprotein. Importantly, save for four patient, LVP fractions contained large amount of apoB, with on average more than 1x10(6) apoB molecules per HCV RNA genome. As there is one apoB molecule per TRL, this ratio suggested that most LVP are nucleocapsid-free, envelope glycoprotein-containing subviral particles. LVP and TRL had similar composition of triacylglycerol and phospholipid classes. Conclusion: LVP are a mixed population of particles, comprising predominantly subviral particles that represent a distinct class of modified lipoproteins within the TRL family. (HEPATOLOGY 2012.).