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Mutations at the CXCR4 interaction sites for AMD3100 influence anti‐CXCR4 antibody binding and HIV‐1 entry
Author(s) -
Hatse Sigrid,
Princen Katrien,
Vermeire Kurt,
Gerlach Lars-Ole,
Rosenkilde Mette M.,
Schwartz Thue W.,
Bridger Gary,
De Clercq Erik,
Schols Dominique
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00609-4
Subject(s) - cxcr4 , infectivity , monoclonal antibody , mutagenesis , mutation , virology , virus , asparagine , lentivirus , antibody , cxcr4 antagonist , human immunodeficiency virus (hiv) , biology , wild type , receptor , microbiology and biotechnology , chemistry , genetics , mutant , gene , amino acid , viral disease , chemokine
The interaction of the CXCR4 antagonist AMD3100 with its target is greatly influenced by specific aspartate residues in the receptor protein, including Asp 171 and Asp 262 . 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 Asp 262 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 Asp 262 of CXCR4, pointing to a different mode of interaction of wild‐type versus AMD3100‐resistant virus with CXCR4.