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Cover photograph (Copyright © 2009, American Society for Microbiology. All Rights Reserved.): Amino acid residues in the V3 loop (surface representation) and C4 region (grey loop) of the human immunodeficiency virus type 1 gp120 envelope glycoprotein bind to the N terminus (yellow ribbon) of CCR5 in a step required for viral entry. Small-molecule antagonists of CCR5, such as vicriviroc, inhibit entry by locking CCR5 in a conformation not recognized by HIV-1. Mutations in gp120 that confer vicriviroc resistance enhance dependence on the N terminus of CCR5 for entry. This effect is consistent with increased H bonding (grey-dotted lines) between gp120 residues R305 (V3 loop) and S437 (C4 region) with the N terminus of CCR5. (See related article on p. 12151).