Assembly of CCR5 with gp120 inhibits the HIV infectivity specifically in T cells.

For the entry of R5 human immunodeficiency virus type 1 (HIV-1) into target cells, CCR5 functions as a coreceptor following the binding of the envelope glycoprotein gp120 to the receptor CD4. While CD4 is known to be strongly downregulated after infection, the fate of CCR5 post-infection remains unclear. We investigated the surface expression of CCR5 on PM1/CCR5 cells following infection with HIV-1. Flow cytometry using anti-CCR5 MAb (T21/8 and 2D7) revealed that CCR5 was not downregulated on the surface of infected cells. Notably, CCR5 was found to be coassembled with HIV-1 Gag at the viral budding sites. A specific subset of CCR5, designated as CCR5, which is recognized by T21/8 but not 2D7, was significantly colocalized with gp120 on the cell surface. Virions incorporating CCR5 were immunoprecipitated using T21/8 MAb but not with 2D7 Mab, indicating that CCR5 was incorporated into progeny virions. The efficiency of CCR5 incorporation into virions was positively correlated with the level of CCR5 expression on the cell surface. Moreover, incorporation efficiency was approximately 83-fold higher in CD4 T cells than in adherent CCR5 cells. Furthermore, the incorporation of CCR5 into HIV-1 virions resulted in a 25% decrease in viral infectivity. These findings suggest that CCR5 may have a detrimental effect during the late stage of the HIV-1 replication cycle.