Wh. Gong et al., MONOCYTE CHEMOTACTIC PROTEIN-2 ACTIVATES CCR5 AND BLOCKS CD4 CCR5-MEDIATED HIV-1 ENTRY/REPLICATION/, The Journal of biological chemistry, 273(8), 1998, pp. 4289-4292
Human immunodeficiency virus, type I (HIV-1) cell-type tropism is dict
ated by chemokine receptor usage: T-cell line tropic viruses use CXCR4
, whereas monocyte tropic viruses primarily use CCR5 as fusion corecep
tors. CC chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP
-1 beta, and RANTES (regulated on activation normal T cell expressed a
nd secreted) inhibit CD4/CCR5-mediated HIV-1 cell fusion, MCP-2 is als
o a member of the CC chemokine subfamily and has the capacity to inter
act with at least two receptors including CCR-1 and CCR2B. In an effor
t to further characterize the binding properties of MCP-2 on leukocyte
s, we observed that MCP-2, but not MCP-1, effectively competed with MI
P-1 beta for binding to monocytes, suggesting that MCP-2 may interact
with CCR5, As predicted, MCP-2 competitively inhibited MIP-1 beta bind
ing to HEK293 cells stably transfected with CCR5 (CCR5/293 cells). MCP
-2 also bound to and induced chemotaxis of CCR5/293 cells with a poten
cy comparable with that of MIP-1 beta. Confocal microscopy indicates t
hat MCP-2 caused remarkable and dose-dependent internalization of CCR5
in CCR5/ 293 cells. Furthermore, MCP-2 inhibited the entry/replicatio
n of HIV-1ADA in CCR5/293 cells coexpressing CD4. These results indica
ted that MCP-2 uses CCR5 as one of its functional receptors and is an
additional potent natural inhibitor of HIV-1.