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Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike. | Wen et al. Retrovirology 2010 7 79 http www.retrovirology.eom content 7 1 79 RETR0VIR0L0GY RESEARCH Open Access GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike 1 2 11 2 1 Michael Wen Reetakshi Arora Huiqiang Wang Lihong Liu Jason T Kimata Paul Zhou Abstract Background Identification of broad neutralization epitopes in HIV-1 envelope spikes is paramount for HIV-1 vaccine development. A few broad neutralization epitopes identified so far are present on the surface of native HIV-1 envelope spikes whose recognition by antibodies does not depend on conformational changes of the envelope spikes. However HIV-1 envelope spikes also contain transiently-exposed neutralization epitopes which are more difficult to identify. Results In this study we constructed single chain Fvs scFvs derived from seven human monoclonal antibodies and genetically linked them with or without a glycosyl-phosphatidylinositol GPI attachment signal. We show that with a GPI attachment signal the scFvs are targeted to lipid rafts of plasma membranes. In addition we demonstrate that four of the GPI-anchored scFvs but not their secreted counterparts neutralize HIV-1 with various degrees of breadth and potency. Among them GPI-anchored scFv X5 exhibits extremely potent and broad neutralization activity against multiple clades of HIV-1 strains tested. Moreover we show that GPI-anchored scFv 4E10 also exhibited more potent neutralization activity than its secretory counterpart. Finally we demonstrate that expression of GPI-anchored scFv X5 in the lipid raft of plasma membrane of human CD4 T cells confers longterm resistance to HIV-1 infection HIV-1 envelope-mediated cell-cell fusion and the infection of HIV-1 captured and transferred by human DCs. Conclusions Thus GPI-anchored scFv could be used as a general and effective way to identify antibodies that react with transiently-exposed neutralization epitopes in envelope proteins of
