Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1

被引:122
作者
de Witte, Lot
Bobardt, Michael
Chatterji, Udayan
Degeest, Gisele
David, Guido
Geijtenbeek, Teunis B. H.
Gallay, Philippe
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[2] VU Amsterdam Univ, Med Ctr, Dept Mol Cell Biol & Immunol, NL-1007 MB Amsterdam, Netherlands
[3] Katholieke Univ Leuven VIB, Dept Human Genet, B-3000 Louvain, Belgium
关键词
D O I
10.1073/pnas.0703747104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dendritic cells (DCs) efficiently capture HIV-1 and mediate transmission to T cells, but the underlying molecular mechanism is still being debated. The C-type lectin DC-SIGN is important in HIV-1 transmission by DCs. However, various studies strongly suggest that another HIV-1 receptor on DCs is involved in the capture of HIV-1. Here we have identified syndecan-3 as a major HIV-1 attachment receptor on DCs. Syndecan-3 is a DC-specific heparan sulfate (HS) proteoglycan that captures HIV-1 through interaction with the HIV-1 envelope glycoprotein gp120. Syndecan-3 stabilizes the captured virus, enhances DC infection in cis, and promotes transmission to T cells. Removal of the HSs from the cell surface by heparinase III or by silencing syndecan-3 by siRNA partially inhibited HIV-1 transmission by immature DCs, whereas neutralizing both syndecan-3 and DC-SIGN completely abrogated HIV-1 capture and subsequent transmission. Thus, HIV-1 exploits both syndecan-3 and DC-SIGN to mediate HIV-1 transmission, and an effective microbicide should target both syndecan-3 and DC-SIGN on DCs to prevent transmission.
引用
收藏
页码:19464 / 19469
页数:6
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