Binding of Free and Immune Complex-Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System.
Binding of Free and Immune Complex-Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System.
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游离丙型肝炎病毒和免疫复合物相关丙型肝炎病毒与红细胞的结合是由补体系统介导的。
DOI：
10.1002/hep.30087
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Allison,RobertD
中科院分区：
文献类型：
--
作者：
Salam,KaziAbdus;Wang,RichardY;Grandinetti,Teresa;DeGiorgi,Valeria;Alter,HarveyJ;Allison,RobertD
红细胞结合循环免疫复合物（IC）并促进IC从循环中清除。慢性丙型肝炎病毒（HCV）感染与IC相关疾病相关。在这项研究中，我们研究了HCV和HCV-IC与红细胞结合和解离的动力学和机制。将细胞培养物产生的HCV与健康献血者的红细胞混合，并对红细胞相关病毒颗粒进行定量。使用纯化的补体蛋白、补体耗竭血清和补体受体抗体研究补体介导的HCV-红细胞结合。使用来自慢性HCV感染患者的纯化HCV特异性免疫球蛋白G（IgG）研究补体介导的HCV-IC/红细胞结合。在不存在抗体的情况下，加入补体活性人血清后，HCV与红细胞的结合增加了200 - 1，000倍。游离HCV的调理作用在10分钟内发生，在20 - 30分钟观察到与红细胞的峰结合。补体蛋白C1是结合所必需的，而C2、C3和C4显著增强结合。补体受体1（CR 1，CD 35）抗体阻断了HCV与从慢性感染HCV患者和健康献血者分离的红细胞的结合。与未结合的HCV相比，HCV-IC显著增强补体介导的与红细胞的结合。补体调理的HCV从红细胞中的解离依赖于因子I的存在。HCV释放的因子I结合优先CD 19 +B细胞相比，其他leukocytes.Conclusion：这些结果表明，补体介导的免费和IC-相关的HCV的红细胞上的CR 1的结合，并提供了一个机制的基本原理，研究的差异表型表达的HCV-IC相关疾病。
Erythrocytes bind circulating immune complexes (ICs) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC‐related disorders. In this study, we investigated the kinetics and mechanism of HCV and HCV‐IC binding to and dissociation from erythrocytes. Cell culture‐produced HCV was mixed with erythrocytes from healthy blood donors, and erythrocyte‐associated virus particles were quantified. Purified complement proteins, complement‐depleted serum, and complement receptor antibodies were used to investigate complement‐mediated HCV‐erythrocyte binding. Purified HCV‐specific immunoglobulin G (IgG) from a chronic HCV‐infected patient was used to study complement‐mediated HCV‐IC/erythrocyte binding. Binding of HCV to erythrocytes increased 200‐ to 1,000‐fold after adding complement active human serum in the absence of antibody. Opsonization of free HCV occurred within 10 minutes, and peak binding to erythrocytes was observed at 20‐30 minutes. Complement protein C1 was required for binding, whereas C2, C3, and C4 significantly enhanced binding. Complement receptor 1 (CR1, CD35) antibodies blocked the binding of HCV to erythrocytes isolated from chronically infected HCV patients and healthy blood donors. HCV‐ICs significantly enhanced complement‐mediated binding to erythrocytes compared to unbound HCV. Dissociation of complement‐opsonized HCV from erythrocytes depended on the presence of Factor I. HCV released by Factor I bound preferentially to CD19+B cells compared to other leukocytes.Conclusion:These results demonstrate that complement mediates the binding of free and IC‐associated HCV to CR1 on erythrocytes and provide a mechanistic rationale for investigating the differential phenotypic expression of HCV‐IC–related disease.
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