Preferential Attachment of HIV Particles to Activated and CD45RO+CD4+T Cells

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Abstract
We have studied the binding of biotinylated HIV particles to various cell lines and peripheral blood mononuclear cells (PBMCs). Viruses were harvested from cultures of cell surface-biotinylated cells productively infected with HIV-IIIB. Labeled HIV particles bound to and infected CD4+ cell lines and PBMCs. The interaction between gp120 and CD4 contributed in part to HIV binding to CD4+ cells. However, HIV binding was for the most part independent of CD4 expression and sensitive to polyanion inhibition. Polyanion-sensitive interactions involved heparan sulfate in cell lines but not in primary T cells. Interestingly, HIV binding to primary cells was heterogeneous and targeted discrete subsets of CD4+ and CD4- cells. The CD4+ T cell subset that displayed high HIV-binding capacity contained mostly CD4+CD45RO+ cells, whereas the subset showing undetectable HIV binding contained higher proportions of CD4+CD45RO- cells. Consistently, purified CD4+CD45RO- cells or purified CD4+ T cells with low virus-binding capacity showed lower HIV entry and delayed HIV replication when compared with purified CD4+CD45RO+ or purified CD4+ T cells with high virus-binding capacity, respectively. Our data suggest that the binding of HIV to cell surface-expressed CD4 might be inefficient in a subset of CD4+ T cells and that increased binding of HIV to activated and CD4+CD45RO+ cells may contribute to the higher susceptibility of these cells to HIV infection.