title: Biochemical and HIV-1 coreceptor properties of K26R, a new CCR5 Variant in China's Sichuan population.
abstract: Despite multiple exposures to HIV-1, some individuals remain uninfected. This resistance to HIV infection has been associated with homozygosity for a 32-basepair deletion in the CCR5 receptor gene. This variant is frequent in caucasians but extremely rare in Asians and Africans. Identifying variations in the CCR5 gene that affect susceptibility to HIV infection in non-caucasians is therefore of great interest. In this report, we identify 5 CCR5 coding region variants in a Chinese population. The K26R mutation is an undescribed gene variant, whereas 228delK was already found in caucasians and G106R, C178R, and R223Q were previously described in Asian populations and functionally analyzed. As the function of K26R was still unknown, we focused our work on studying its chemokine receptor activity and HIV coreceptor properties compared with wild-type CCR5 and G106R, an already analyzed mutant taken as another control. We observed that K26R displayed alteration in MIP1-beta/CCL4 and RANTES/CCL5 ligand binding and exhibited a slightly decrease for HIV coreceptor properties.
authors.affiliation: INSERM U543, CHU Pitié-Salpétrière, 75013 Paris, France.
authors.forename: Liying
authors.initials: L
authors.lastname: Ma
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Dudoit
authors.forename: Ton
authors.initials: T
authors.lastname: Tran
authors.forename: Hui
authors.initials: H
authors.lastname: Xing
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pancino
authors.forename: Georges
authors.initials: G
authors.lastname: Bismuth
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.forename: Corinne
authors.initials: C
authors.lastname: Capoulade-Métay
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000635:transmission; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000276:immunology; D019742:Chemokines, CC / Q000276:immunology; D002681:China; D017931:DNA Primers; D005434:Flow Cytometry; D014644:Genetic Variation; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics*; D014162:Transfection
chemical_list: C066507:CCL4 protein, human; C483024:CCL5 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5