Functional analysis of naturally occurring mutations in the open reading frame of CCR5 in HIV-infected Chinese patients and healthy controls.
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.
Zhao
Xiu-Ying
XY
HIV Research Laboratories, Department of Microbiology, University of Hong Kong, Hong Kong, China.
Lee
Shui-Shan
SS
Wong
Ka-Hing
KH
Chan
Kenny C W
KC
Ng
Fai
F
Chan
Chris C S
CC
Han
Dan
D
Yam
Wing-Cheong
WC
Yuen
Kwok-Yung
KY
Ng
Mun-Hon
MH
Zheng
Bo-Jian
BJ
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
D019713:Receptors, CCR5