of symptomatic West Nile virus infection

West Nile virus (WNV) is a reemerging pathogen that causes fatal encephalitis in several species, including mouse and human. Recently, we showed that the chemokine receptor CCR5 is critical for survival of mice infected with WNV, acting at the level of leukocyte traffi cking to the brain. To test whether this receptor is also protective in man, we determined the frequency of CCR5�� 32 , a defective CCR5 allele found predominantly in Caucasians, in two independent cohorts of patients, one from Arizona and the other from Colorado, who had laboratory-confi rmed, symptomatic WNV infection. The distribution of CCR5�� 32 in a control population of healthy United States Caucasian random blood donors was in Hardy-Weinberg equilibrium and CCR5�� 32 homozygotes represented 1.0% of the total group (n = 1,318). In contrast, CCR5�� 32 homozygotes represented 4.2% of Caucasians in the Arizona cohort (odds ratios [OR] = 4.4 [95% confi dence interval [CI], 1.6– 11.8], P = 0.0013) and 8.3% of Caucasians in the Colorado cohort (OR = 9.1 [95% CI, 3.4–24.8], P < 0.0001). CCR5�� 32 homozygosity was signifi cantly associated with fatal outcome in the Arizona cohort (OR = 13.2 [95% CI, 1.9–89.9], P = 0.03). We conclude that CCR5 mediates resistance to symptomatic WNV infection. Because CCR5 is also the major HIV coreceptor, these fi ndings have important implications for the safety of CCR5blocking agents under development for HIV/AIDS.