Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2.
Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2.
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DOI：
10.1038/ncomms13882
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发表时间：
2017-01-09
影响因子：
16.6
通讯作者：
Machida K
中科院分区：
文献类型：
--
作者：
Chen CL;Huang JY;Wang CH;Tahara SM;Zhou L;Kondo Y;Schechter J;Su L;Lai MM;Wakita T;Cosset FL;Jung JU;Machida K
丙型肝炎病毒（HCV）感染B细胞一直是一个有争议的话题。为了检查HCV是否具有通过对嗜淋巴细胞HCV感染特异性的共受体的遗传决定的嗜淋巴细胞性，我们建立了来自HCV阳性B细胞淋巴瘤的嗜肝和嗜淋巴细胞HCV株的感染性克隆和嵌合病毒。嗜淋巴细胞性HCV株的病毒包膜和5′-UTR序列是其嗜淋巴细胞性的主要原因。病毒传感器RIGI的沉默或microRNA-122的过表达促进了B细胞中的持续病毒复制。通过cDNA文库筛选，我们确定了免疫细胞特异性的共刺激受体B7.2（CD 86）作为嗜淋巴细胞HCV的共受体。HCV感染B细胞可抑制对抗原刺激的回忆反应。共同受体B7.2使嗜淋巴细胞HCV感染记忆B细胞，导致记忆B细胞功能抑制和HCV感染宿主的持续HCV感染。丙型肝炎病毒（HCV）对B细胞的感染知之甚少，但被认为会导致淋巴组织增生性疾病。在此，Chen等人鉴定了CD 86作为嗜淋巴细胞HCV的共受体，并表明HCV感染抑制记忆B细胞功能。
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. Infection of B cells by hepatitis C virus (HCV) is poorly understood, but is thought to result in lymphoproliferative disorders. Here, Chen et al. identify CD86 as co-receptor for lymphotropic HCV and show that HCV infection inhibits memory B-cell function.