CCR5 deficiency increases risk 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 trafficking to the brain. To test whether this receptor is also protective in man, we determined the frequency of CCR5Delta32, 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-confirmed, symptomatic WNV infection. The distribution of CCR5Delta32 in a control population of healthy United States Caucasian random blood donors was in Hardy-Weinberg equilibrium and CCR5Delta32 homozygotes represented 1.0% of the total group (n = 1,318). In contrast, CCR5Delta32 homozygotes represented 4.2% of Caucasians in the Arizona cohort (odds ratios [OR] = 4.4 [95% confidence 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). CCR5Delta32 homozygosity was significantly 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 findings have important implications for the safety of CCR5-blocking agents under development for HIV/AIDS.

Radiation hybrid map of the porcine genome comprising 2035 EST loci.

The IMpRH(7000-rad) radiation hybrid panel was used to map 2035 expressed sequence tags (ESTs) at a minimum LOD score of 4.0. A total of 134 linkage groups covers 57,192 cR or 78% of the predicted size of the porcine and 71% of the human genome, respectively. Approximately 81% (1649) of the porcine ESTs were annotated against the NCBI nonredundant database; 1422 mapped in silico to a location in build 35.1 of the human genome sequence (HGS) and 1185 to a gene and location in build 35.1 HGS. The map revealed 40 major breaks in synteny (1.00e (-25 )and lower) with the human genome, 37 of which fall within a single chromosome. At this improved level of resolution and coverage, porcine chromosomes (SSC) 2, 5, 6, 7, 12, and 14 remain "gene-rich" and homologous to human chromosomes (HSA) 17, 19, and 22, while SSC 1, 8, 11, and X have been confirmed to correspond to the "gene-deserts" on HSA 18, 4, 13, and X.