The LD78β isoform of MIP-1α is the most potent CCR5 agonist and HIV-1-inhibiting chemokine

LD78 alpha and LD78 beta are 2 highly related nonallelic genes that code for different isoforms of the human CC chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha). Two molecular forms of natural LD78 beta (7.778 and 7.793 kDa) were identified from conditioned media of stimulated peripheral blood mononuclear cells. Although LD78 alpha and LD78 beta only differ in 3 amino acids, both LD78 beta variants were 100-fold more potent chemoattractants for mouse lymphocytes than was LD78 alpha. On the contrary, LD78 beta was only 2-fold more efficient than LD78 alpha in chemoattracting human lymphocytes and monocytes. Using CC chemokine receptor-transfected cells, both molecular forms of LD78 beta proved to be much more potent than LD78 alpha in inducing an intracellular calcium rise through CCR5. Compared with LD78 alpha and RANTES, this preferential binding of LD78 beta to CCR5 resulted in a 10- to 50-fold higher potency in inhibiting infection of peripheral blood mononuclear cells by CCR5-using (R5) HIV-1 strains. To date, LD78 beta is the most potent chemokine for inhibiting HIV-1 infection, and can be considered as a potentially important drug candidate for the treatment of infection with R5 HIV-1 strains.