Human erythrocytes selectively bind and enrich infectious HIV-1 virions.
Human erythrocytes selectively bind and enrich infectious HIV-1 virions.
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DOI：
10.1371/journal.pone.0008297
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发表时间：
2009-12-14
期刊：
影响因子：
3.7
通讯作者：
Alving CR
中科院分区：
文献类型：
--
作者：
Beck Z;Brown BK;Wieczorek L;Peachman KK;Matyas GR;Polonis VR;Rao M;Alving CR
虽然CD 4（+）细胞是血液中HIV感染的主要靶细胞，但HIV-1与红细胞的补体非依赖性结合以及Duffy血型抗原的可能作用引起了争议。为了研究与红细胞结合的问题，将HIV-1与来自30名健康白细胞分离术供体的红细胞在体外孵育，并通过p24分析和HIV-1的吸附以及对CD 4（+）靶细胞的感染性降低来确定结合。所有的细胞，无论血型类型，结合HIV-1 p24。典型的红细胞制剂结合<2.4%的添加的p24，但红细胞选择性地去除基本上所有的病毒感染性，如通过降低CD 4（+）靶细胞的感染所确定的;然而，细胞相关的HIV-1通过反式感染比未吸附的病毒感染CD 4（+）细胞的效率高约100倍。通过用EDTA处理细胞释放所有结合的HIV-1 p24，并通过在洗涤含有结合的HIV-1的红细胞期间加入Ca 2+和Mg 2+来优化结合。尽管红细胞制剂中少量的污染性白细胞也与HIV-1 p24结合，但与CD 4无显著结合，因此似乎结合发生在非CD 4位点的白细胞上。此外，结合发生在红细胞血影上，其中污染的白细胞已经被去除。结果表明，在不存在补体的情况下，与HIV-1体外孵育的红细胞对所有感染性HIV-1病毒体（与非感染性或降解的病毒体相反）的吸附差异不受血型的影响，并且结合依赖于二价阳离子。通过与树突状细胞上的DC-SIGN结合的HIV-1类比，红细胞结合的HIV-1可能包含用于允许细胞的反式感染的重要表面储库。
Although CD4(+) cells represent the major target for HIV infection in blood, claims of complement-independent binding of HIV-1 to erythrocytes and the possible role of Duffy blood group antigen, have generated controversy. To examine the question of binding to erythrocytes, HIV-1 was incubated in vitro with erythrocytes from 30 healthy leukapheresis donors, and binding was determined by p24 analysis and adsorption of HIV-1 with reduction of infectivity for CD4(+) target cells. All of the cells, regardless of blood group type, bound HIV-1 p24. A typical preparation of erythrocytes bound <2.4% of the added p24, but erythrocytes selectively removed essentially all of the viral infectivity as determined by decreased infection of CD4(+) target cells; however, cell-associated HIV-1 was approximately 100-fold more efficient, via trans infection, than unadsorbed virus for infection of CD4(+) cells. All of the bound HIV-1 p24 was released by treatment of the cells with EDTA, and binding was optimized by adding Ca2+ and Mg2+ during the washing of erythrocytes containing bound HIV-1. Although the small number of contaminating leukocytes in the erythrocyte preparation also bound HIV-1 p24, there was no significant binding to CD4, and it thus appears that the binding occurred on leukocytes at non-CD4 sites. Furthermore, binding occurred to erythrocyte ghosts from which contaminating leukocytes had been previously removed. The results demonstrate that erythrocytes incubated in vitro with HIV-1 differentially adsorb all of the infectious HIV-1 virions (as opposed to non-infectious or degraded virions) in the absence of complement and independent of blood group, and binding is dependent on divalent cations. By analogy with HIV-1 bound to DC-SIGN on dendritic cells, erythrocyte-bound HIV-1 might comprise an important surface reservoir for trans infection of permissive cells.
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