Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages

Macrophages are thought to represent one of the first cell types in the bod y to be infected during the early stage of human immunodeficiency virus typ e 1 (HIV-1) transmission and represent a potential viral reservoir in vivo. Thus, an understanding of HIV-1 attachment to these cells is fundamental t o 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, othe r 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 require d 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 hepa ran sulfate proteoglycans (HSPGs) serve as the main class of attachment rec eptors for HIV-1 on macrophages. Most importantly, we demonstrate that a si ngle family of HSPGs, the syndecans, efficiently mediates HIV-1 attachment and represents an abundant class of attachment receptors on macrophages.