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

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.