Prevention of lymphotropic hepatitis C virus infection by blocking antibodies

通过对152例连续入选患者的前瞻性研究，我们测定了患者血清中慢性丙型肝炎病毒（HCV）与淋巴细胞系HPB-Ma的结合能力，发现它是干扰素治疗的主要决定因素之一（J Hepatology）。由于HCV通过中和抗体失去感染性，我们测定了血清中无抗体病毒粒子的数量，并测定了38例患者的包膜2蛋白高变区的氨基酸序列，其中22例为1b型，16例为2a/2b型。我们发现，1b型患者中有少量无抗体病毒粒子，所有2a/2b型感染患者中无抗体病毒粒子的数量与无抗体病毒粒子的数量无关，但在1b型患者中无抗体病毒粒子的数量与无抗体病毒粒子的数量无关为了确定HCV的细胞嗜性，我们建立了与肝细胞系HuH 7结合的HCV的测量方法。大多数患者的HCV可与HPB-Ma和HuH 7两种细胞系结合，而部分患者的HCV仅与肝细胞系HuH 7结合。没有HCV仅与淋巴细胞系HPB-Ma结合。干扰素治疗效果与肝细胞系HuH 7的结合能力无关，但与淋巴细胞系HPB-Ma有关。现在，我们正在检查高变区以分析细胞嗜性和针对淋巴细胞感染的阻断抗体。

We measured the binding ability of chronic hepatitis C virus (HCV) to the lymphocyte cell line HPB-Ma in the patient's serum, and found that it was one of the major determinant of interferon therapy by the prospective study of 152 consecutively enrolled patients (J Hepatology). As the HCV loose their infectivity by neutralized antibodies, we measured the quantity of antibody-free virion in the serum, and determined the amino acid sequence of hypervariable region of envelope 2 protein for the 38 patients ; 22 genotype 1b and 16 genotype 2a/2b. We found the consensus sequence of hypervariable region in the genotype 1b patients with a small amount of antibody-free virion and the all patients with a genotype 2a/2b infection regardless of the quantity of antibody-free virion, but not in the genotype 1b patients with a high amount of antibody-free virions (J Med Virol).To determine the cell tropism of HCV, we established the measurement method of HCV that bound to the hepatocyte cell line HuH7. The HCV in the majority of patients could bind to the both cell lines HPB-Ma and HuH7, while the HCV in some patients could bind only to the hepatocyte cell line HuH7. There are no HCV that could bind only to the lymphocyte cell line HPB-Ma. The interferon treatment efficacy was well related not to the binding ability to the hepatocyte cell line HuH7 but to the lymphocyte cell line HPB-Ma. Now, we are examining the hypervariable region to analyze the cell tropism and the blocking antibody against the lymphocyte infection.