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- Title
Mutations at the CXCR4 interaction sites for AMD3100 influence anti-CXCR4 antibody binding and HIV-1 entry
- Authors
Hatse, Sigrid; Princen, Katrien; Vermeire, Kurt; Gerlach, Lars-Ole; Rosenkilde, Mette M.; Schwartz, Thue W.; Bridger, Gary; De Clercq, Erik; Schols, Dominique
- Abstract
The interaction of the CXCR4 antagonist AMD3100 with its target is greatly influenced by specific aspartate residues in the receptor protein, including Asp171 and Asp262. We have now found that aspartate-to-asparagine substitutions at these positions differentially affect the binding of four different anti-CXCR4 monoclonal antibodies as well as the infectivity of diverse human immunodeficiency virus type 1 (HIV-1) strains and clinical isolates. Mutation of Asp262 strongly decreased the coreceptor efficiency of CXCR4 for wild-type but not for AMD3100-resistant HIV-1 NL4.3. Thus, resistance of HIV-1 NL4.3 to AMD3100 is associated with a decreased dependence of the viral gp120 on Asp262 of CXCR4, pointing to a different mode of interaction of wild-type versus AMD3100-resistant virus with CXCR4.
- Subjects
GENETIC mutation; PROTEINS
- Publication
FEBS Letters, 2003, Vol 546, Issue 2/3, p300
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(03)00609-4