Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2GI2 as probed by Fc-tagged gp120

被引:28
作者
Binley, James M.
Ngo-Abdalla, Stacie
Moore, Penny
Bobardt, Michael
Chatterji, Udayan
Gallay, Philippe
Burton, Dennis R.
Wilson, Ian A.
Elder, John H.
de Parseval, Aymeric
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[2] Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA
[3] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa
[4] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[5] Scripps Res Inst, Dept Immunol & Mol Biol, La Jolla, CA 92037 USA
[6] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[7] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1186/1742-4690-3-39
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope ( Env) with various receptors, we assessed the inhibitory properties of various anti-Env monoclonal antibodies (mAbs) in binding assays. To assist in detecting Env in attachment assays, we generated Fc fusions of full-length wild-type gp120 and several variable loop-deleted gp120s. Through investigation of the inhibition of Env binding to cell lines expressing CD4, CCR5, DC-SIGN, syndecans or combinations thereof, we found that the broadly neutralizing mAb, 2G12, directed to a unique carbohydrate epitope of gp120, inhibited Env-CCR5 binding, partially inhibited Env-DC-SIGN binding, but had no effect on Env-syndecan association. Furthermore, 2G12 inhibited Env attachment to primary monocyte-derived dendritic cells, that expressed CD4 and CCR5 primary HIV receptors, as well as DC-SIGN, and suggested that the dual activities of 2G12 could be valuable in vivo for inhibiting initial virus dissemination and propagation.
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页数:15
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