The LD78 beta isoform of MIP-1 alpha is the most potent CC-chemokine in inhibiting CCR5-dependent human immunodeficiency virus type 1 replication in human macrophages

The CC-chemokines RANTES, macrophage inflammatory protein 1 alpha (MIP-1 al pha), and MIP-1 beta are natural ligands for the CC-chemokine receptor CCR5 . MIP-1 alpha, also known as LD78 alpha, has an isoform, LD78 beta, which w as identified as the product of a nonallelic gene. The two isoforms differ in only 3 amino acids. LD78 beta cvas recently reported to be a much more p otent CCR5 agonist than LD78 alpha and RANTES in inducing intracellular Ca2 + signaling and chemotaxis. CCR5 is expressed by human monocytes/macrophage s (M/M) and represents an important coreceptor for macrophage-tropic, CCR5- using (R5) human immunodeficiency virus type 1 (HIV-1) strains to infect th e cells. We compared the antiviral activities of LD78 beta and the other CC -chemokines in M/M. LD78 beta at 100 ng/ml almost completely blocked HIV-1 replication, while at the same concentration LD78a had only weak antiviral activity. Moreover, when HIV-1 infection in M/M was monitored by a flow cyt ometric analysis using p24 antigen intracellular staining, LD78 beta proved to be the most antivirally active of the chemokines. RANTES, once describe d as the most potent chemokine in inhibiting R5 HIV-1 infection, was found to be considerably less active than LD78 beta. LD78 beta strongly downregul ated CCR5 expression in M/M, thereby explaining its potent antiviral activi ty.