Prevention of lymphotropic hepatitis C virus infection by blocking antibodies

我们测定了慢性丙型肝炎病毒(HCV)与患者血清中淋巴细胞系HPB-Ma的结合能力，通过对152例连续入选的患者的前瞻性研究发现，它是干扰素治疗的主要决定因素之一。当中和抗体使丙型肝炎病毒失去感染力时，我们测定了血清中无抗体病毒粒子的数量，并测定了38例患者的包膜蛋白高变区氨基酸序列，其中1b型22例，2a/2b型16例。我们在1b型患者和2a/2b型ALL患者中发现了一致的高变区序列，但在1b型患者中发现了少量无抗体病毒粒子的存在，而在1b型患者中发现了大量无抗体病毒粒子(J Med Virol)。为了确定丙型肝炎病毒的细胞嗜性，我们建立了与肝细胞系Huh7结合的丙型肝炎病毒的测量方法。大多数患者的丙型肝炎病毒可与HPB-Ma和Huh7两种细胞结合，而部分患者的丙型肝炎病毒仅与肝细胞系Huh7结合。不存在仅与淋巴细胞系HPB-Ma结合的丙型肝炎病毒。干扰素的疗效与肝细胞系HuH7的结合力无关，与淋巴细胞系HPB-Ma的结合力密切相关。现在，我们正在检测高变区，以分析细胞的趋向性和针对淋巴细胞感染的封闭抗体。

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.