Interaction between allelic variation in IL12B and CCR5 affects the development of AIDS: IL12B/CCR5 interaction and HIV/AIDS.

Objective: IL-12 is involved in immune surveillance and response that links the innate and adaptive arms of the immune system. Among its many effects, IL-12 increases the cell surface expression of the CCR5 co-receptor for R5 strains of HIV-1, which are predominantly involved in HIV-1 transmission and spread. In the present study we investigated the effect of epistasis between allelic variants of CCR5 and IL12B on the susceptibility to HIV-1 infection and HIV-1 disease progression. Methods: HIV-1-positive patients were genotyped for ILI2Bpro from two groups of HIV-1 seroincident patients from Western Australia (n=101 and 200), longitudinal clinical data were available for one of the Western Australian cohorts for a period of over 12 years and a group of seroprevalent individuals from Sydney (n= 112). A group of ethnically matched healthy volunteers (n=200) was also genotyped as controls. Comparison of allele frequencies between HIV-1 patients and controls was performed to determine the influence on susceptibility to HIV-1 infection, and regression analysis was used to determine the influence on disease progression. Results: Individuals positive for CCR5 Delta 32 and who carry the IL12Bpro1.1 genotype were underrepresented across all three independent HIV-1-positive cohorts [odds ratio 0.5; 95% confidence interval (CI) 0.28-0.97; P=0.038]. CCR5wt/wt and IL 12Bpro2.2 individuals progressed to AIDS at a significantly faster rate than other CCR5 and IL12Bpro groups (hazards ratio 3.24; 95% CI 1.9-15.1; P=0.002). Conclusion: Epistatic interaction between allelic variants of CCR5 and IL 12Bpro exert a significant influence on the clinical outcome of HIV-1 infection. (c) 2007 Lippincott Williams & Wilkins.