Diaz Olivier, Delers François, Maynard Marianne, Demignot Sylvie, Zoulim Fabien, Chambaz Jean, Trépo Christian, Lotteau Vincent, André Patrice
IFR 128 Biosciences Lyon Gerland, INSERM U503, 21 avenue Tony Garnier, 69007 Lyon, France.
Université Pierre et Marie Curie, INSERM, UMRS 505, Paris, France.
J Gen Virol. 2006 Oct;87(Pt 10):2983-2991. doi: 10.1099/vir.0.82033-0.
Hepatitis C virus (HCV) in cell culture has a density comparable to that of other members of the family Flaviviridae, whereas in vivo infectious particles are found partially in low-density fractions, associated with triacylglycerol (TG)-rich lipoproteins (TRLs). In the blood of infected patients, HCV circulates as heterogeneous particles, among which are lipo-viroparticles (LVPs), globular particles rich in TG and containing viral capsid and RNA. The dual viral and lipoprotein nature of LVPs was addressed further with respect to apolipoprotein composition and post-prandial dynamic lipid changes. The TRLs exchangeable apoE, -CII and -CIII, but not the high-density lipoprotein apoA-II, were present on LVPs, as well as the viral envelope proteins. apoB100 and -B48, the two isoforms of the non-exchangeable apoB, were represented equally on LVPs, despite the fact that apoB48 was barely detectable in the plasma of these fasting patients. This indicates that a significant fraction of plasma HCV was associated with apoB48-containing LVPs. Furthermore, LVPs were enriched dramatically and rapidly in triglycerides after a fat meal. As apoB48 is synthesized exclusively by the intestine, these data highlight the preferential association of HCV with chylomicrons, the intestine-derived TRLs. These data raise the question of the contribution of the intestine to the viral load and suggest that the virus could take advantage of TRL assembly and secretion for its own production and of TRL fate to be delivered to the liver.
丙型肝炎病毒（HCV）在细胞培养中的密度与黄病毒科其他成员相当，而在体内，感染性颗粒部分存在于低密度组分中，与富含三酰甘油（TG）的脂蛋白（TRL）相关。在受感染患者的血液中，HCV以异质性颗粒形式循环，其中包括脂病毒颗粒（LVP），即富含TG且含有病毒衣壳和RNA的球状颗粒。就载脂蛋白组成和餐后动态脂质变化而言，对LVP的病毒和脂蛋白双重性质进行了进一步研究。LVP上存在TRL可交换的载脂蛋白E、-CII和-CIII，但不存在高密度脂蛋白载脂蛋白A-II，同时也存在病毒包膜蛋白。不可交换载脂蛋白B的两种异构体载脂蛋白B100和-B48在LVP上的含量相当，尽管在这些空腹患者的血浆中几乎检测不到载脂蛋白B48。这表明血浆中相当一部分HCV与含载脂蛋白B48的LVP相关。此外，高脂餐后LVP中的甘油三酯显著且迅速富集。由于载脂蛋白B48仅由肠道合成，这些数据突出了HCV与乳糜微粒（源自肠道的TRL）的优先关联。这些数据提出了肠道对病毒载量贡献的问题，并表明该病毒可能利用TRL的组装和分泌进行自身产生，并利用TRL的命运将其输送至肝脏。
