CCR5 deficiency is a risk factor for early clinical manifestations of West Nile virus infection but not for viral transmission

J Infect Dis. 2010 Jan 15;201(2):178-85. doi: 10.1086/649426.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Blood Donors
  • Case-Control Studies
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Odds Ratio
  • Receptors, CCR5 / deficiency*
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / immunology
  • United States
  • West Nile Fever / immunology*


  • Receptors, CCR5