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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.

Authors :
Zhao XY
Lee SS
Wong KH
Chan KC
Ng F
Chan CC
Han D
Yam WC
Yuen KY
Ng MH
Zheng BJ
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.

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