Biochemical and HIV-1 coreceptor properties of K26R, a new CCR5 Variant in China's Sichuan population.
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.
Ma
Liying
L
INSERM U543, CHU Pitié-Salpétrière, 75013 Paris, France.
Dudoit
Yasmine
Y
Tran
Ton
T
Xing
Hui
H
Chen
Jianping
J
Pancino
Gianfranco
G
Bismuth
Georges
G
Debré
Patrice
P
Shao
Yiming
Y
Theodorou
Ioannis
I
Capoulade-Métay
Corinne
C
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
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