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Functional analysis of naturally occurring mutations in the open reading frame of CCR5 in HIV-infected Chinese patients and healthy controls.
- Source :
-
Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2005 Apr 15; Vol. 38 (5), pp. 509-17. - Publication Year :
- 2005
-
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.
- Subjects :
- Amino Acid Sequence
Amino Acid Substitution
Asian People genetics
China
Gene Frequency
Humans
Models, Molecular
Molecular Sequence Data
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Protein Conformation
Reference Values
Transcription, Genetic
HIV Infections genetics
Mutation
Open Reading Frames
Receptors, CCR5 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1525-4135
- Volume :
- 38
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of acquired immune deficiency syndromes (1999)
- Publication Type :
- Academic Journal
- Accession number :
- 15793360
- Full Text :
- https://doi.org/10.1097/01.qai.0000151004.19128.4a