Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1.
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.
de Witte
Lot
L
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bobardt
Michael
M
Chatterji
Udayan
U
Degeest
Gisèle
G
David
Guido
G
Geijtenbeek
Teunis B H
TB
Gallay
Philippe
P
D000906:Antibodies / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D034741:RNA, Small Interfering / Q000494:pharmacology; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053670:Syndecan-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D053586:Virus Internalization
D000906:Antibodies; D034741:RNA, Small Interfering; D015728:Receptors, HIV; D053670:Syndecan-3