Interference with the Signaling Capacity of Cc Chemokine Receptor 5 Can Compromise Its Role as an HIV-1 Entry Coreceptor in Primary T Lymphocytes

In this issue of The Journal of Experimental Medicine 1, Alfano et al. report the surprising results that pertussis toxin (PTX) as well as its cellular binding subunit, the B-oligomer, each blocked entry of monotropic (R5) strains of HIV-1 in primary T lymphocytes. Treatment of primary T cells with B-oligomer, unlike treatment of T cell lines, blocked calcium mobilization in response to the CCR5 chemokine ligand macrophage inflammatory protein-1β (MIP-1β), but had no effect on cell surface expression of CCR5 and binding of MIP-1β or HIV-1 envelope gp120. Alfano et al. further demonstrate that B-oligomer blocks cocapping of CCR5 and CD4 induced by R5 HIV-1, but does not affect cocapping of CXCR4 and CD4 after incubation with T tropic (X4) virus. They documented that the B-oligomer signals by itself and induces calcium mobilization in primary T lymphocytes. Based...