Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele

Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15276-9. doi: 10.1073/pnas.2435085100. Epub 2003 Nov 25.

Abstract

The high frequency, recent origin, and geographic distribution of the CCR5-Delta 32 deletion allele together indicate that it has been intensely selected in Europe. Although the allele confers resistance against HIV-1, HIV has not existed in the human population long enough to account for this selective pressure. The prevailing hypothesis is that the selective rise of CCR5-Delta 32 to its current frequency can be attributed to bubonic plague. By using a population genetic framework that takes into account the temporal pattern and age-dependent nature of specific diseases, we find that smallpox is more consistent with this historical role.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles*
  • Child
  • Child, Preschool
  • Disease Outbreaks
  • Gene Frequency
  • Genes, Dominant
  • HIV
  • HIV Infections / genetics*
  • HIV Seropositivity
  • Humans
  • Infant
  • Middle Aged
  • Models, Genetic
  • Models, Statistical
  • Plague / genetics*
  • Receptors, CCR5 / genetics*
  • Smallpox / genetics*
  • Time Factors

Substances

  • Receptors, CCR5