Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

Variable loop 3 (V3) of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and P. vivax can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the P. knowlesi alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of P. vivax and P. knowlesi erythrocyte binding proteins.A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.Human immunodeficiency virus type 1 (HIV-1) and the human malaria parasite Plasmodium vivax both use chemokine receptors in obligate steps of cell invasion. HIV-1 uses CCR5 and CXCR4 as the major coreceptors for infecting CD4+ cells (macrophages, T-lymphocytes, and other cell types) in vivo, while P. vivax uses the Duffy antigen receptor for chemokines (DARC) for invading human reticulocytes [1,2]. Alleles of CCR5 and DARC associated with decreased functional protein expression confer resistance to HIV and P. vivax, respectively, and chemokines can inhibit in vitro infection by either pathogen [1,3-5]. The HIV surface glycoprotein (SU, gp120) undergoes a conformational change upon binding to CD4 and then presents a chemokine receptor binding surface predicted to include a hydrophobic core surrounded by positive residues contributed by conserved and variable regions including the base of the V3 loop. The V3 loop putatively extends toward the cell surface and contacts the chemokine receptor at a second site in the second extracellular loop. Individual amino acid mutations in the V3 loop can change chemokine receptor specificity.P. vivax and the simian mala