The J6JFH1 strain of hepatitis C virus infects human B-cells with low replication efficacy.
The J6JFH1 strain of hepatitis C virus infects human B-cells with low replication efficacy.
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DOI：
10.1089/vim.2013.0140
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发表时间：
2014-07
期刊：
影响因子：
2.2
通讯作者：
Masato Nakai;T. Seya;M. Matsumoto;K. Shimotohno;N. Sakamoto;Hussein H. Aly
中科院分区：
文献类型：
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作者：
Masato Nakai;T. Seya;M. Matsumoto;K. Shimotohno;N. Sakamoto;Hussein H. Aly
摘要丙型肝炎病毒感染是世界范围内严重的健康问题，可导致肝细胞癌或终末期肝病。目前使用聚乙二醇化干扰素、利巴韦林和NS3/4A蛋白水解酶抑制剂可以在大量患者中获得良好的预后，但目前仍没有有效的丙型肝炎疫苗。丙型肝炎病毒强烈感染肝脏中的肝细胞。然而，肝外表现，如混合性冷球蛋白血症，一种以B细胞增殖为特征的全身性免疫复合物介导的疾病，可能演变为明显的B细胞性非霍奇金淋巴瘤。丙型肝炎病毒核糖核酸常与外周血淋巴细胞结合，提示可能与外周血单核细胞，尤其是B细胞与丙型肝炎病毒相互作用。B细胞丙型肝炎病毒感染一直是一个有争议的问题，而丙型肝炎病毒体外感染系统的新进展表明，外切体可以传递丙型肝炎病毒基因组来支持感染。我们的目的是阐明原代B细胞对丙型肝炎病毒感染的易感性，并研究其功能效应。本文通过逆转录聚合酶链式反应检测丙型肝炎病毒负链RNA和NS5A蛋白，发现重组丙型肝炎病毒J6JFH1株能感染正常人外周血中分离的人B细胞。我们还显示了在B细胞丙型肝炎病毒感染后，I型干扰素可以阻断丙型肝炎病毒的复制。虽然在B淋巴细胞中复制丙型肝炎病毒的效率低于肝细胞系(Huh7)细胞，但我们的结果清楚地表明，没有其他非B细胞的人B淋巴细胞实际上可以感染丙型肝炎病毒，这种相互作用导致B细胞的先天免疫反应的诱导，并改变这些细胞对凋亡的反应。
Abstract Hepatitis C virus (HCV) infection is a serious health problem worldwide that can lead to hepatocellular carcinoma or end-stage liver disease. Current treatment with pegylated interferon, ribavirin, and NS3/4A protease inhibitor would lead to a good prognosis in a large population of patients, but there is still no effective vaccine for HCV. HCV robustly infects hepatocytes in the liver. However, extrahepatic manifestations such as mixed cryoglobulinemia, a systemic immune complex-mediated disorder characterized by B-cell proliferation, which may evolve into overt B-cell non-Hodgkin's lymphoma, have been demonstrated. HCV-RNA is often found to be associated with peripheral blood lymphocytes, suggesting a possible interaction with peripheral blood mononuclear cells (PBMCs), especially B-cells with HCV. B-cell HCV infection was a matter of debate for a long time, and the new advance in HCV in vitro infectious systems suggest that exosome can transmit HCV genome to support "infection." We aimed to clarify the susceptibility of primary B-cells to HCV infection, and to study its functional effect. In this article, we found that the recombinant HCV J6JFH1 strain could infect human B-cells isolated from the peripheral blood of normal volunteers by the detection of both HCV-negative-strand RNA by reverse transcription polymerase chain reaction, and NS5A protein. We also show the blocking of HCV replication by type I interferon after B-cell HCV infection. Although HCV replication in B-lymphocytes showed lower efficiency, in comparison with hepatocyte line (Huh7) cells, our results clearly demonstrate that human B-lymphocytes without other non-B-cells can actually be infected with HCV, and that this interaction leads to the induction of B-cells' innate immune response, and change the response of these cells to apoptosis.