CCR5 deficiency increases risk of symptomatic West Nile virus infection.

摘要: West Nile virus (WNV) is a reemerging pathogen that causes fatal encephalitis in several species, including mouse and human. Recently, we showed the chemokine receptor CCR5 critical for survival of mice infected with WNV, acting at level leukocyte trafficking to brain. To test whether this also protective man, determined frequency CCR5Δ32, defective allele found predominantly Caucasians, two independent cohorts patients, one from Arizona other Colorado, who had laboratory-confirmed, symptomatic WNV infection. The distribution CCR5Δ32 control population healthy United States Caucasian random blood donors was Hardy-Weinberg equilibrium homozygotes represented 1.0% total group (n = 1,318). In contrast, 4.2% Caucasians cohort (odds ratios [OR] 4.4 [95% confidence interval [CI], 1.6–11.8], P 0.0013) 8.3% Colorado (OR 9.1 CI, 3.4–24.8], < 0.0001). homozygosity significantly associated outcome 13.2 1.9–89.9], 0.03). We conclude mediates resistance Because major HIV coreceptor, these findings have important implications safety CCR5-blocking agents under development HIV/AIDS.