CXCR4 engagement is required for HIV-1-induced L-selectin shedding

The chemokine receptor, CXCR4, serves as the primary coreceptor for entry of T-cell tropic human immunodeficiency virus (HIV). Binding of either the CXC-chemokine, stromal-derived factor 1α (SDF-1α), or a CXCR4 antagonist, AMD3100, to CXCR4 inhibits infection of CD4⁺ T cells by T-tropic HIV-1, although only SDF-1α triggers T-cell signaling cascades. We have previously demonstrated that ligation of CD4 by T-cell tropic HIV-1 NL4-3 induces metalloproteinase-dependent L-selectin (CD62L) shedding on resting CD4⁺ T cells. However, the role of CXCR4 in HIV-induced L-selectin shedding is unclear. Here, we show that L-selectin shedding induced by HIV-1 NL4-3 is completely reversed by AMD3100, but not SDF-1α, although SDF-1α alone does not induce L-selectin shedding. These results indicate that engagement of both CD4 and CXCR4 is required for HIV-induced shedding of L-selectin on primary resting CD4⁺ T cells.