P. Menten et al., The LD78 beta isoform of MIP-1 alpha is the most potent CCR5 agonist and HIV-1-inhibiting chemokine, J CLIN INV, 104(4), 1999, pp. R1-R5
LD78 alpha and LD78 beta are 2 highly related nonallelic genes that code fo
r different isoforms of the human CC chemokine macrophage inflammatory prot
ein-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 periphe
ral blood mononuclear cells. Although LD78 alpha and LD78 beta only differ
in 3 amino acids, both LD78 beta variants were 100-fold more potent chemoat
tractants for mouse lymphocytes than was LD78 alpha. On the contrary, LD78
beta was only 2-fold more efficient than LD78 alpha in chemoattracting huma
n 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 resu
lted in a 10- to 50-fold higher potency in inhibiting infection of peripher
al 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 b
e considered as a potentially important drug candidate for the treatment of
infection with R5 HIV-1 strains.