title: Functional analysis of naturally occurring mutations in the open reading frame of CCR5 in HIV-infected Chinese patients and healthy controls.
abstract: We studied polymorphism of the HIV coreceptor CC chemokine receptor (CCR) 5 in 1099 Chinese adults residing in Hong Kong, including 785 HIV-negative healthy donors and 314 HIV-positive patients. Ten mutants in the CCR5 open reading frame were identified, 7 of which were nonsynonymous. The frequencies of these alleles did not show a significant difference between HIV patients and healthy controls. G106R, Delta32, R223Q, 299(FS), and S336I were cloned from prevalent mutant genes, and their effects on HIV infection were analyzed by a series of in vitro experiments to determine their transcription levels, expression levels, conformational changes, and HIV coreceptor function. R223Q is the most prevalent CCR5 mutant in ethnic Chinese, with a frequency of 0.046, which does not affect HIV infection in vitro, however. The S336I mutant also does not affect its transcription, expression, or HIV coreceptor function. Similar to 299(FS), the mutant G106R located in the third transmembrane domain results in diminished HIV coreceptor function in vitro through conformation changes in ECL2.
authors.affiliation: HIV Research Laboratories, Department of Microbiology, University of Hong Kong, Hong Kong, China.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Zhao
authors.forename: Shui-Shan
authors.initials: SS
authors.lastname: Lee
authors.forename: Ka-Hing
authors.initials: KH
authors.lastname: Wong
authors.forename: Kenny C W
authors.initials: KC
authors.lastname: Chan
authors.forename: Fai
authors.initials: F
authors.lastname: Ng
authors.forename: Chris C S
authors.initials: CC
authors.lastname: Chan
authors.forename: Dan
authors.initials: D
authors.lastname: Han
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Yam
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
authors.forename: Mun-Hon
authors.initials: MH
authors.lastname: Ng
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002681:China; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D019713:Receptors, CCR5 / Q000235:genetics*; D012016:Reference Values; D014158:Transcription, Genetic
chemical_list: D019713:Receptors, CCR5