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 predominant phenotype of HIV in early infection. The CCR5 agonists macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, 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 chemokine 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 CD4(+) lymphocytes and can specifically block R5 HIV-1.
Yang
Otto O
OO
AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. oyang@mednet.ucla.edu
Garcia-Zepeda
Eduardo A
EA
Walker
Bruce D
BD
Luster
Andrew D
AD
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054412:Chemokine CCL8; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology*; D037342:Pertussis Toxin; D019713:Receptors, CCR5 / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
C515453:CCL8 protein, human; D054412:Chemokine CCL8; D018945:Monocyte Chemoattractant Proteins; D019713:Receptors, CCR5; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D002118:Calcium