CCR5 deficiency is a risk factor for early clinical manifestations of West Nile virus infection but not for viral transmission.
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.
Lim
Jean K
JK
Molecular Signaling Section, Laboratory of Molecular Immunology, Laboratory of Cellular and Molecular Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
McDermott
David H
DH
Lisco
Andrea
A
Foster
Gregory A
GA
Krysztof
David
D
Follmann
Dean
D
Stramer
Susan L
SL
Murphy
Philip M
PM
D000328:Adult; D001782:Blood Donors; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D014481:United States; D014901:West Nile Fever / Q000276:immunology*
D019713:Receptors, CCR5