Role of the CCR5 delta 32 allele in resistance to HIV-1 infection in west Africa.
OBJECTIVE
To determine the frequency of the mutant CCR5 delta 32 allele in high-risk HIV-seronegative Africans as compared with the general African population, and to assess its in vitro protective efficacy against HIV-1 infection.


METHODS
In the homozygous form, the CCR5 delta 32 allele confers resistance to macrophage-tropic (M-tropic) strains of HIV-1. Assuming that genetic characteristics favoring HIV resistance would prevail in a high-risk HIV-seronegative population, we examined the CCR5 genotypes of female commercial sex workers (CSWs) from Dakar, Senegal, who have remained uninfected for an elongated period.


METHODS
The CCR5 genetic profile of study participants was determined by polymerase chain reaction (PCR) amplification of genomic DNA followed by sequencing. Peripheral blood mononuclear cells (PBMCs) were infected with different strains of HIV-1 and monitored by p24 enzyme-linked immunosorbent assay (ELISA).


RESULTS
We confirmed the presence of two CCR5wt/delta 32 genotypes among 139 individuals (1.44%). PBMCs from these 2 heterozygous individuals were also found to be less susceptible to in vitro infection by an M-tropic HIV-1 primary isolate.


CONCLUSIONS
Evidence was found of an increased prevalence of the CCR5wt/delta 32 genotype in a high-risk HIV-seronegative cohort in West Africa. Furthermore, reduced susceptibility to HIV-1 infection among heterozygous individuals supports a role for 32-bp CCR5 deletion in HIV-1 resistance.
Kokkotou
E
E
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115-6017, USA.
Philippon
V
V
Guèye-Ndiaye
A
A
Mboup
S
S
Wang
W K
WK
Essex
M
M
Kanki
P
P
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000821:virology*; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D018023:HIV Seronegativity / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics*; D012307:Risk Factors; D012675:Senegal; D011477:Sex Work
D019713:Receptors, CCR5