Factor I-mediated processing of complement fragments on HIV immune complexes targets HIV to CR2-expressing B cells and facilitates B cell-mediated transmission of opsonized HIV to T cells

Factor I-mediated processing of complement fragments on HIV immune complexes targets HIV to CR2-expressing B cells and facilitates B cell-mediated transmission of opsonized HIV to T cells
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DOI:
10.4049/jimmunol.177.5.3469
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发表时间:
2006-09-01
影响因子:
4.4
通讯作者:
Stoiber, Heribert
Stoiber, Heribert
中科院分区:
医学2区
文献类型:
--
作者:
Banki, Zoltan;Wilflingseder, Doris;Stoiber, Heribert

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我们的研究表明,补体调理的HIV通过C3b片段与人红细胞(E)上的补体I型受体结合,随后由正常人血清介导的HIV与E的快速分离,这种释放依赖于病毒表面是否存在表明C3b片段转化为IC3b和C3d的因子I。这反过来又导致调理的HIV与表达CR2的B细胞有效结合,从而促进B细胞介导的HIV向T细胞的传播。这些数据为HIV的补体调理提供了一个新的动态观点,提示病毒与E的结合可能是一种短暂的现象,而因子I介导的C3b到Ic3b和C3d在HIV上的处理以病毒为靶向补体受体2型表达细胞。因此,在HIV感染者的滤泡树突状细胞和/或B细胞上,由于辅助因子活性,血清中的因子I和CR1在血清中的协同作用可能是产生C3d调理的感染性HIV储备库的重要因素。
Our study demonstrates that binding of complement-opsonized HIV to complement receptor type I on human erythrocytes (E) via C3b fragments is followed by a rapid normal human serum-mediated detachment of HIV from E. The release was dependent on the presence of factor I indicating a conversion of C3b fragments to iC3b and C3d on the viral surface. This in turn resulted in an efficient binding of opsonized HIV to CR2-expressing B cells, thus facilitating B cell-mediated transmission of HIV to T cells. These data provide a new dynamic view of complement opsonization of HIV, suggesting that association of virus with E might be a transient phenomenon and the factor I-mediated processing of C3b to iC3b and C3d on HIV targets the virus to complement receptor type 2-expressing cells. Thus, factor I in concert with CR1 on E and factor H in serum due to their cofactor activity are likely to be important contributors for the generation of C3d-opsonized infectious HIV reservoirs on follicular dendritic cells and/or B cells in HIV-infected individuals.