CONCISE COMMUNICATION Monocyte Chemoattractant Protein–2 (CC Chemokine Ligand 8) Inhibits Replication of Human Immunodeficiency Virus Type 1 via CC Chemokine Receptor 5

CC chemokine receptor 5 (CCR5) is a coreceptor for cellular entry of monocyte-tropic (R5) strains of human immunodeficiency virus (HIV) type 1, which has been implicated as the predom-inant phenotype of HIV in early infection. The CCR5 agonists macrophage inflammatory protein (MIP) – 1a, MIP-1b, and RANTES (regulated on activation, normally T cell – expressed and –secreted) have been shown to block replication of R5 virus in vitro and have gained attention as potential antiviral factors. However, a few reports have suggested that other chemokines may also block R5 HIV-1, including monocyte chemoattractant protein (MCP) – 2 (CC chemo-kine ligand 8). We demonstrate that MCP-2 specifically inhibits replication of R5 HIV-1 and that this activity is additive to that of RANTES. Furthermore, MCP-2 induces a robust, pertussis toxin–sensitive calcium flux in primary lymphocytes, and cross-desensitization studies indicate that MCP-2 acts via CCR5. These data confirm that MCP-2 is a ligand for CCR5 on CD4þ lym-phocytes and can specifically block R5 HIV-1. Analysis of CD8þ T cell supernatants led to identification of macrophage inflammatory protein (MIP)–1a, MIP-1b, and RANTES as the first well-characterized soluble antiviral factor