Binding of HIV-1 to RBCs involves the Duffy Antigen Receptors for Chemokines (DARC)

The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on-activation, normal T cell-expressed and -secreted (RANTES), but not macrophage inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian individuals via DARC making RBCs able to transmit HIV to peripheral blood mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is inhibited by treating these cells with recombinant RANTES, but not with recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.