BACKGROUND: West Nile virus (WNV) is a neurotropic flavivirus transmitted to humans by mosquito vectors. Homozygosity for CCR5Delta32, a complete loss-of-function mutation in CC chemokine receptor 5 (CCR5), has been previously associated with severe symptomatic WNV infection in patients who present with clinical disease; however, whether it acts at the level of initial infection or in promoting clinical progression is unknown. METHODS: Here, we address this gap in knowledge by comparing CCR5Delta32 distribution among US blood donors identified through a comprehensive blood supply screening program (34,766,863 donations from 2003 through 2008) as either WNV true positive (634 WNV-positive cases) or false positive (422 WNV-negative control participants). All subjects self-reported symptoms occurring during the 2 weeks following blood donation using a standardized questionnaire. RESULTS: No difference was observed in CCR5Delta32 homozygous frequency between the WNV-positive cases and WNV-negative control participants. However, CCR5Delta32 homozygosity was associated in cases but not controls with clinical symptoms consistent with WNV infection (P = .002). CONCLUSIONS: CCR5 deficiency is not a risk factor for WNV infection per se, but it is a risk factor for both early and late clinical manifestations after infection. Thus, CCR5 may function normally to limit disease due to WNV infection in humans.
BACKGROUND:West Nile virus (WNV) is a neurotropic flavivirus transmitted to humans by mosquito vectors. Homozygosity for CCR5Delta32, a complete loss-of-function mutation in CC chemokine receptor 5 (CCR5), has been previously associated with severe symptomatic WNV infection in patients who present with clinical disease; however, whether it acts at the level of initial infection or in promoting clinical progression is unknown. METHODS: Here, we address this gap in knowledge by comparing CCR5Delta32 distribution among US blood donors identified through a comprehensive blood supply screening program (34,766,863 donations from 2003 through 2008) as either WNV true positive (634 WNV-positive cases) or false positive (422 WNV-negative control participants). All subjects self-reported symptoms occurring during the 2 weeks following blood donation using a standardized questionnaire. RESULTS: No difference was observed in CCR5Delta32 homozygous frequency between the WNV-positive cases and WNV-negative control participants. However, CCR5Delta32 homozygosity was associated in cases but not controls with clinical symptoms consistent with WNV infection (P = .002). CONCLUSIONS:CCR5 deficiency is not a risk factor for WNV infection per se, but it is a risk factor for both early and late clinical manifestations after infection. Thus, CCR5 may function normally to limit disease due to WNV infection in humans.
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