15th International AIDS Conference Bangkok, Thailand - July 11-16, 2004

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1107)

Capoulade-Metay C, Ma L, Truong XL, Dudoit Y, Versmisse P, Nguyen NV, Nguyen M, Scott-Algara D, Barre-Sinoussi F, Debre P, Pancino G, Theodorou I
INSERM, Paris, France

BACKGROUND: Despite multiple exposure to HIV-1, some individuals remain uninfected. This resistance has been associated with homozygosity for a 32-base pair deletion in the CCR5 receptor gene. This variant is frequent in Caucasians, but extremely rare in Asians. Identifying variations in the CCR5 gene affecting susceptibility to HIV infection in South East Asian is therefore of great interest. Vietnamese intravascular drug users (IDU) exposed to HIV-1, and Cambodian sexual partners of HIV-1 patients, remaining persistently HIV-1 negative, were enrolled for this study.

METHODS: Vietnamese group consists of HIV-1 infected IDU, HIV-1 exposed IDU but uninfected and healthy subjects. Cambodian group is formed by HIV-1 infected subjects, seronegative partners and healthy subjects. CCR5 mutation detection was done on their DNA by PCR then dHPLC and sequencing. Detected variants were cloned to permit cell lines transfection for receptor and HIV-1 coreceptor functional studies. Form some of them, CD4+ cells were used in HIV-1 infection assay.

RESULTS: We reports 5 CCR5 variants in these 2 populations, with 3 undescribed and 2 already found in other Asian groups, of which one has already known functions. All these variants exhibit low frequencies, but, interestingly, 2 of them show altered receptor properties (poor expression and MIP-1[beta binding) and lower HIV coreceptor efficiency (reduced cell-cell fusion and infectivity). Noteworthy, CD4+ cells from heterozygous individuals bearing those 2 variants show reduced susceptibility to HIV-1 infection. Discussion: This CCR5 genetic study of HIV-1 exposed but uninfected Vietnamese and Cambodian subjects shows that 2 of the described mutants displayed significant modifications of their receptor and coreceptor functions that could affect HIV-1 transmission. Also, despite the limited epidemiological data, it is of note that these particular mutants are found exclusively in the HIV-1 negative subjects in a heterozygous state. We might then speculate on their potential role in HIV resistance specifically in Asian populations.

040711
TuOrA1107

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