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 1 alpha (SDF-1 alpha), or a CXCR4 antagonist, AMD3100, to CXCR4 inhibits infection of CD4(+) T cells by T-tropic HIV-1, although only SDF-1 alpha 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-1 alpha, although SDF-1 alpha 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.
Wang
JiangFang
J
Division of Rheumatology, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA.
Marschner
Susanne
S
Finkel
Terri H
TH
D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D019041:L-Selectin