Université de Lyon, France; INSERM U851, Lyon, France.
Hepatology. 2012 Jul;56(1):39-48. doi: 10.1002/hep.25628. Epub 2012 Apr 25.
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.
LVPs are a mixed population of particles, comprising predominantly subviral particles that represent a distinct class of modified lipoproteins within the TRL family.
丙型肝炎病毒（HCV）颗粒将病毒和脂蛋白部分结合在一起形成混合脂蛋白颗粒（LVPs）。细胞培养产生的 HCV（HCVcc）和体外鉴定的 LVPs 主要区别在于其载脂蛋白（apo）B 含量，HCVcc 的 apoB 含量低，而 LVPs 的 apoB 含量高。载脂蛋白 B 产生的细胞系可组装和分泌无核衣壳的亚病毒 LVP。为了确定 HCV 感染个体中是否存在这种亚病毒颗粒，从 36 例丙型肝炎患者的低密度血浆部分用蛋白 A 沉淀与免疫球蛋白结合的 LVP，并测定其脂质含量、载脂蛋白谱和病毒组成。用定量 PCR 测定 LVP 中的 HCV RNA，并计算 apoB 和 HCV 基因组拷贝数的摩尔比。通过电喷雾电离/串联质谱法测定来自四个患者的 LVP 脂质组。用蛋白 A 纯化的 LVP 至少含有包膜糖蛋白 E2 和 E2 特异性抗体。LVPs 存在于每个患者中，其特征是脂质含量高，存在富含甘油三酯的脂蛋白（TRLs）的载脂蛋白，HCV RNA 和病毒糖蛋白。重要的是，除了四个患者，LVPs 部分含有大量的 apoB，平均每个 HCV RNA 基因组有超过 1×106 apoB 分子。因为每个 TRL 有一个 apoB 分子，这个比例表明大多数 LVP 是无核衣壳、含包膜糖蛋白的亚病毒颗粒。LVPs 和 TRLs 的三酰甘油和磷脂类组成相似。
LVPs 是一种混合颗粒群体，主要由亚病毒颗粒组成，这些亚病毒颗粒代表 TRL 家族中一种独特的修饰脂蛋白。
