PMID- 18040049 OWN - NLM STAT- MEDLINE DCOM- 20080118 LR - 20220223 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 104 IP - 49 DP - 2007 Dec 4 TI - Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1. PG - 19464-9 AB - 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. FAU - de Witte, Lot AU - de Witte L AD - Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Bobardt, Michael AU - Bobardt M FAU - Chatterji, Udayan AU - Chatterji U FAU - Degeest, Gisele AU - Degeest G FAU - David, Guido AU - David G FAU - Geijtenbeek, Teunis B H AU - Geijtenbeek TB FAU - Gallay, Philippe AU - Gallay P LA - eng GR - R21 AI071952/AI/NIAID NIH HHS/United States GR - R33 AI071952/AI/NIAID NIH HHS/United States GR - R33 AI076005/AI/NIAID NIH HHS/United States GR - AI 071952/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20071126 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antibodies) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, HIV) RN - 0 (Syndecan-3) SB - IM MH - Antibodies/pharmacology MH - Dendritic Cells/*immunology/virology MH - *HIV-1 MH - Humans MH - RNA, Small Interfering/pharmacology MH - Receptors, HIV/antagonists & inhibitors/genetics/*metabolism MH - Syndecan-3/antagonists & inhibitors/genetics/*metabolism MH - T-Lymphocytes/*immunology/virology MH - *Virus Internalization PMC - PMC2148312 COIS- The authors declare no conflict of interest. EDAT- 2007/11/28 09:00 MHDA- 2008/01/19 09:00 PMCR- 2008/06/04 CRDT- 2007/11/28 09:00 PHST- 2007/11/28 09:00 [pubmed] PHST- 2008/01/19 09:00 [medline] PHST- 2007/11/28 09:00 [entrez] PHST- 2008/06/04 00:00 [pmc-release] AID - 0703747104 [pii] AID - 8220 [pii] AID - 10.1073/pnas.0703747104 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19464-9. doi: 10.1073/pnas.0703747104. Epub 2007 Nov 26.