New CCR5 variants associated with reduced HIV coreceptor function in southeast Asia.
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 gene for the CCR5 receptor. This variant occurs frequently in Caucasians but is extremely rare in Asians or Africans.


OBJECTIVE
To identify variations in CCR5 receptor gene that affect susceptibility to HIV infection in non-Caucasians.


METHODS
CCR5 coding region polymorphisms were screened in three groups of Vietnamese subjects: 47 HIV-1 infected intravascular drug users, 50 highly HIV-1-exposed but seronegative intravascular drug users and 37 HIV-1-unexposed seronegative individuals. DNA was analysed by denaturing high performance liquid chromatography; this was followed by examination of the biochemical and HIV coreceptor properties of the coding regions.


RESULTS
Five CCR5 coding region variants were identified in this Vietnamese population. The S185R, I254T and C269F mutations have not been previously described; G106R and R223Q have already been found in other Asian populations, but the functional properties of G106R is not known. These variants differed in biochemical and HIV coreceptor properties. S185R and I254T variants had receptor and coreceptor activities comparable to that of the wild type, whereas C269F and G106R behaved differently. This latter pair are poorly expressed at the cell surface, weakly bind macrophage inflammatory protein 1beta (CCL4) and RANTES (CCL5), and display reduced HIV-1 coreceptor efficiency.


CONCLUSIONS
Among the five CCR5 variants found in this Vietnamese population, G106R and C269F displayed significant modifications of their receptor and coreceptor properties, which may contribute to susceptibility to HIV-1 infection and/or disease progression within this population.
Capoulade-Métay
Corinne
C
INSERM U543, CHU Pitié-Salpétrière, Institut Cochin, Paris, France. metay@chups.jussieu.fr
Ma
Liying
L
Truong
Lien X
LX
Dudoit
Yasmine
Y
Versmisse
Pierre
P
Nguyen
Ngai V
NV
Nguyen
Marie
M
Scott-Algara
Daniel
D
Barré-Sinoussi
Françoise
F
Debré
Patrice
P
Bismuth
Georges
G
Pancino
Gianfranco
G
Theodorou
Ioannis
I
D002160:Cambodia; D002460:Cell Line; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015658:HIV Infections / Q000150:complications / Q000235:genetics*; D018023:HIV Seronegativity / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics*; D019966:Substance-Related Disorders / Q000150:complications / Q000235:genetics; D014744:Vietnam
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D004279:DNA, Viral; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5