Complement mediates the binding of HIV to erythrocytes
Complement mediates the binding of HIV to erythrocytes
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DOI：
10.4049/jimmunol.173.6.4236
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发表时间：
2004-09-15
影响因子：
4.4
通讯作者：
Schifferli, JA
中科院分区：
文献类型：
--
作者：
Horakova, E;Gasser, O;Schifferli, JA
即使在抗逆转录病毒治疗下，血浆中的病毒检测不到，一部分HIV仍与红细胞相关。本工作的目的是进一步表征这种关联在体外。我们开发了一种体外模型来研究HIV-1与红细胞粘附的相关因素。将放射性标记的HIV-1（HIV）和预先形成的HIV-1/抗HIV免疫复合物（HIV-IC）在各种人血清中调理，使用蔗糖密度梯度超离心纯化，并与人红细胞孵育。我们观察到，当在正常人血清中调理时，不仅HIV-IC，而且HIV与红细胞结合，尽管HIV的粘附性低于HIV-IC。当补体系统被阻断时，粘附被取消，但在低丙种球蛋白血症血清中维持。补体缺乏的血清表明，这两种途径的补体是重要的最佳坚持。在C1 q缺陷型血清中未观察到粘附，并且当使用抗因子D抗体阻断旁路途径时，HIV的粘附减少。抗补体受体1的单克隆抗体可抑制粘附。在超生理浓度下，纯化的C1 q介导一小部分HIV和HIV-IC与红细胞的结合。总之，当暴露于补体时，HIV-IC与其他类型的IC一样与红细胞结合。特别令人感兴趣的是，单独的HIV也以补体/补体受体1依赖性方式与红细胞结合。因此，红细胞不仅可以将HIV-IC递送到易受感染的器官，而且还可以释放HIV。这可能在原发性感染的进展中起关键作用。
A fraction of HIV is associated with erythrocytes even when the virus becomes undetectable in plasma under antiretroviral therapy. The aim of the present work was to further characterize this association in vitro. We developed an in vitro model to study the factors involved in the adherence of HIV-1 to erythrocytes. Radiolabeled HIV-1 (HIV) and preformed HIV-1/anti-HIV immune complexes (HIV-IC) were opsonized in various human sera, purified using sucrose density gradient ultracentrifugation, and incubated with human erythrocytes. We observed that, when opsonized in normal human serum, not only HIV-IC, but also HIV, bound to erythrocytes, although the adherence of HIV was lower than that of HIV-IC. The adherence was abolished when the complement system was blocked, but was maintained in hypogammaglobulinemic sera. Complement-deficient sera indicated that both pathways of complement were important for optimal adherence. No adherence was seen in C1q-deficient serum, and the adherence of HIV was reduced when the alternative pathway was blocked using anti-factor D Abs. The adherence could be inhibited by an mAb against complement receptor 1. At supraphysiological concentrations, purified C1q mediated the binding of a small fraction of HIV and HIV-IC to erythrocytes. In conclusion, HIV-IC bound to erythrocytes as other types of IC do when exposed to complement. Of particular interest was that HIV alone bound also to erythrocytes in a complement/complement receptor 1-dependent manner. Thus, erythrocytes may not only deliver HIV-IC to organs susceptible to infection, but free HIV as well. This may play a crucial role in the progression of the primary infection.