4, 5 Indeed, HCV virions with a density <1.06 g/mL are associated with lipoproteins, thus forming hybrid particles known as lipoviral particles (LVPs). These low-density viral particles are globular, rich in triacylglycerol selleck chemicals and total cholesterol (TChol) and contain the viral envelope glycoproteins and nucleocapsid (composed of HCV RNA and core protein).

In addition, LVPs contain all the apolipoproteins (apo) that define the triacylglycerol-rich lipoproteins (TRLs). Indeed, apolipoprotein (apo) B, apoE, apoCI, apoCII, and apoCIII, all of which characterize very low-density, intermediate-density, and low-density lipoproteins (VLDL, IDL, and LDL, respectively), also characterize LVPs (for review, see André et al.6 and Bartenschlager et al.7). Interestingly, the proportions of circulating low-density virus vary widely from patient to patient; in some cases, all HCV RNA is recovered in plasma low-density fractions or is coimmunoprecipitated by apoB-specific antibodies.8 The study of LVPs has been hampered by the absence of an in vitro culture

system that produces find more apoB-associated viral particles. Infectious cell culture–produced HCV (HCVcc) that can be propagated efficiently only in the human hepatoma cell line Huh7 has higher density than in vivo circulating viruses.9 HCVcc are associated with apoE and apoC, but only marginally with apoB, in contrast to ex vivo–characterized LVPs.10, 11 Despite these differences, two sets of evidence further ascertain the role of lipoproteins in HCVcc assembly. First, alteration MCE of the lipoprotein pathway by inhibition of the microsomal

triglyceride transfer protein (MTP) or of the diacylglycerol acyltransferase-1 (DGAT-1) or silencing of apoB or apoE expression decreases the production of infectious HCVcc virions.12-14 Second, the phospholipid compositions of HCVcc and TRL share similar characteristics, whereas they strikingly differ from those of cellular membranes or envelopes of virus that assemble at cellular membranes.15-17 Furthermore, lipoprotein lipases that specifically hydrolyse lipoprotein triacylglycerol modify HCVcc biochemical and physical features and decrease their infectivity.18, 19 Thus, both in vivo–produced and in vitro–produced HCV particles share many characteristics of lipoprotein association, but with differences in the extent of apoB association. Recently, we studied the capacity of cell lines to secrete recombinant envelope glycoproteins E1 and E2.20 Only cell lines that produce TRLs such as HepG2, Huh7, and Caco-2 were able to secrete the envelope glycoproteins, in contrast to cells that do not synthesize lipoproteins. The envelope glycoproteins and apoB were present in the same lipoproteins released from HepG2 and Caco-2, but only marginally or not at all with particles released from Huh7. Poor lipidation of apoB in Huh7 compared with other cell lines might explain these differences.