AIDSWEEKLY Plus; Monday, November 14, 2005
Staff Medical Writers

"Exposed seronegative individuals (ES) with persistent high-risk sexual behavior may be less susceptible to human immunodeficiency virus type 1 (HIV-1) infection because they carry the chemokine receptor (CR) gene alleles CCR5 open reading frame (ORF) Δ32, CCR5 promoter -2459G, or CCR2 ORF 641 (CCR2-641), all of which have been found to diminish HIV-1 infectivity and/or disease progression.

"To investigate this, we determined the haplotypes for these three genetic loci in 93 ES and 247 low-risk control individuals," wrote investigators in the United States.

"To test if protective haplotypes exert their effect by modulating CR expression, we measured the protein expression of CCR5 and CXCR4 on circulating CD4+ T cells and CD14+ monocytes in 71 ES and 92 controls. To avoid investigator bias, the analysis was performed without knowledge of each subject's risk and genotype," researchers said.

"The CCR5 -2459G allele was significantly enriched in ES Caucasian men, who constituted the majority (84%) of the ES cohort, compared to the control Caucasian men (p=0.02).

"This increase was mostly attributable to a higher frequency of the -2459 A/G versus the -2459 A/A genotype in individuals heterozygous for the A32 allele (p=0.012). No protective influence of the CCR2-641 allele was observed," wrote F. Hladik and colleagues at the Fred Hutchinson Cancer Research Center in Seattle.

"The haplotypes CCR5 ORF Δ32/CCR5 -2459A (in complete linkage disequilibrium) and CCR5 ORF wt/CCR5 -2459G had a cumulative negative effect on the expression of CCR5, since we measured significantly reduced CCR5 densities on both T-helper cells and monocytes only when both haplotypes were present.

"Densities of CCR5 on lymphocytes and monocytes were correlated (r=0.59; p<0.0001)," the authors continued, "indicating concordance of CCR5 expression patterns across different cell types."

Hladik concluded that the "CCR5 ORF Δ32/wt-CCR5 -2459 A/G genotype combination offers an advantage in resisting sexual HIV-1 transmission and that this effect is mediated by a relative paucity of CCR5 on potential target cells of HIV-1."

Hladik and colleagues published their study in the Journal of Virology (Combined effect of CCR5-Δ32 heterozygosity and the CCR5 promoter polymorphism-2459 A/G on CCR5 expression and resistance to human immunodeficiency virus type 1 transmission. J Virol. 2005 Sep;79(18):11677-84.

For more information, contact F. Hladik, Fred Hutchinson Cancer Research Center, Program Infectious Disease, Division Clinic Research, 1100 Fairview Avenue N, POB 19024, D3-100, Seattle, WA 98109, USA.

Publisher contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Seattle, Washington, United States, HIV/AIDS, Viral Transmission, Genotype, Infection Resistance, CCR5, Lymphocytes, Monocytes, A/G Genotype Combination.

This article was prepared by AIDS Weekly editors from staff and other reports. Copyright 2005, AIDS Weekly via NewsRx.com.

Reference

Hladik F, Liu H, Speelmon E, et al., "Combined effect of CCR5-Delta32 heterozygosity and the CCR5 promoter polymorphism -2459 A/G on CCR5 expression and resistance to human immunodeficiency virus type 1 transmission." J Virol. 2005 Sep;79(18):11677-84.

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