Description
The two human MIP-1 alpha genes arise by duplication/mutation. They code for MIP-1 alpha isoforms CCL3/LD78 alpha and CCL3L1/LD78 beta, which share 94% amino acid (aa) sequence homology. Whereas the human CCL3/LD78 alpha is a single-copy gene, the human CCL3L1/LD78 beta gene copy number varies within the population. Human CCL3L1/LD78 beta cDNA encodes a 93 aa residue precursor with a 23 aa residue signal peptide that is cleaved to generate a 70 aa mature protein. Human CCL3L1/LD78 beta binds and signals through chemokine receptors CCR1 and CCR5. When compared to CCL3/LD78 alpha, CCL3L1/LD78 beta has higher binding affinity to CCR5, which also functions as a coreceptor for HIV-1 entry. The copy number of CCL3L1 is one of several genetic determinants of HIV-1 susceptibility (4).