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Journal of Virology, October 2001, p. 9187-9200, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9187-9200.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Syndecans Serve as Attachment Receptors for Human Immunodeficiency Virus Type 1 on Macrophages†

Andrew C. S. Saphire,1 Michael D. Bobardt,1 Zhe Zhang,2 Guido David,2 and Philippe A. Gallay1,*

Department of Immunology, The Scripps Research Institute, La Jolla, California 92037,1 and Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium2

Received 7 March 2001/Accepted 28 June 2001

Macrophages are thought to represent one of the first cell types in the body to be infected during the early stage of human immunodeficiency virus type 1 (HIV-1) transmission and represent a potential viral reservoir in vivo. Thus, an understanding of HIV-1 attachment to these cells is fundamental to the development of novel anti-HIV-1 therapies. Although one of the major targets of HIV-1 in vivo---CD4+ T lymphocytes---express high CD4 levels, other major targets such as macrophages do not. We asked in this study whether this low CD4 level on macrophages is sufficient to support HIV-1 attachment to these cells or whether cell surface proteins other than CD4 are required for this process. We show that CD4 alone is not sufficient to support the initial adsorption of HIV-1 to macrophages. Importantly, we find that heparan sulfate proteoglycans (HSPGs) serve as the main class of attachment receptors for HIV-1 on macrophages. Most importantly, we demonstrate that a single family of HSPGs, the syndecans, efficiently mediates HIV-1 attachment and represents an abundant class of attachment receptors on macrophages.

* Corresponding author. Mailing address: Department of Immunology IMM-9, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8180. Fax: (858) 784-8227. E-mail: gallay{at}scripps.edu.

dagger This is publication no. 13562-IMM from the Department of Immunology, The Scripps Research Institute, La Jolla, Calif.

Journal of Virology, October 2001, p. 9187-9200, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9187-9200.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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