Secretory IgA specific for a conserved epitope on gp41 envelope glycoprotein inhibits epithelial transcytosis of HIV-1
Secretory IgA specific for a conserved epitope on gp41 envelope glycoprotein inhibits epithelial transcytosis of HIV-1
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DOI：
10.4049/jimmunol.166.10.6257
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发表时间：
2001-05-15
影响因子：
4.4
通讯作者：
Bomsel, M
中科院分区：
文献类型：
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作者：
Alfsen, A;Iniguez, P;Bomsel, M
作为艾滋病病毒（HIV - 1）最初的黏膜传播途径之一，上皮细胞通过非降解性转胞吞作用将HIV - 1从顶端表面转运至基底外侧表面。当HIV - 1包膜糖蛋白与上皮细胞膜结合时，转胞吞作用启动。在此我们表明，病毒包膜的跨膜gp41亚单位在涉及保守的ELDKWA表位的位点与上皮鞘糖脂半乳糖神经酰胺（Gal Cer）结合，Gal Cer是HIV - 1的一种替代受体。破坏顶端表面含Gal Cer的微区的脂筏结构会抑制HIV - 1的转胞吞作用。免疫学研究证实了保守的ELDKWA六肽在HIV - 1转胞吞作用中的关键作用。来自血清阳性受试者的黏膜IgA（而非IgG）靶向该保守肽，中和gp41与Gal Cer的结合，并阻断HIV - 1的转胞吞作用。这些结果强调了分泌型IgA在设计针对HIV - 1感染的黏膜保护策略中的重要作用。
As one of the initial mucosal transmission pathways of HIV (HIV-1), epithelial cells translocate HIV-1 from apical to basolateral surface by nondegradative transcytosis. Transcytosis is initiated when HIV-1 envelope glycoproteins bind to the epithelial cell membrane. Here we show that the transmembrane gp41 subunit of the viral envelope binds to the epithelial glycosphingolipid galactosyl ceramide (Gal Cer), an alternative receptor for HIV-1, at a site involving the conserved ELDKWA epitope. Disrupting the raft organization of the Gal Cer-containing microdomains at the apical surface inhibited HIV-1 transcytosis. Immunological studies confirmed the critical role of the conserved ELDKWA hexapeptide in HIV-1 transcytosis. Mucosal IgA, but not IgG, from seropositive subjects targeted the conserved peptide, neutralized gp41 binding to Gal Cer, and blocked HIV-1 transcytosis. These results underscore the important role of secretory IgA in designing strategies for mucosal protection against HIV-1 infection.