Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
Nat Commun. 2017 Jan 9;8:13882. doi: 10.1038/ncomms13882.
B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells. By cDNA library screening, we identified an immune cell-specific, co-stimulatory receptor B7.2 (CD86) as a co-receptor of lymphotropic HCV. Infection of B cells by HCV inhibited the recall reaction to antigen stimulation. Together, a co-receptor B7.2 enabled lymphotropic HCV to infect memory B cells, leading to inhibition of memory B-cell function and persistent HCV infection in HCV-infected hosts.
B 细胞感染丙型肝炎病毒（HCV）一直是一个有争议的话题。为了研究 HCV 是否通过感染淋巴亲嗜性 HCV 的共受体具有遗传决定的淋巴亲嗜性，我们建立了一个感染性克隆和来自 HCV 阳性 B 细胞淋巴瘤的亲肝和淋巴亲嗜性 HCV 株的嵌合病毒。淋巴亲嗜性 HCV 株的包膜和 5'-UTR 序列负责其亲淋巴性。病毒传感器 RIGI 的沉默或 microRNA-122 的过表达促进了 B 细胞中持续的病毒复制。通过 cDNA 文库筛选，我们鉴定出免疫细胞特异性共刺激受体 B7.2（CD86）是淋巴亲嗜性 HCV 的共受体。HCV 对 B 细胞的感染抑制了对抗原刺激的回忆反应。总之，共受体 B7.2 使淋巴亲嗜性 HCV 能够感染记忆 B 细胞，导致记忆 B 细胞功能抑制和 HCV 感染宿主中持续的 HCV 感染。
