Reappraisal of the historical selective pressures for the CCR5-Delta32 mutation.

HIV strains are unable to enter macrophages that carry the CCR5-Delta32 deletion; the average frequency of this allele is 10% in European populations. A mathematical model based on the changing demography of Europe from 1000 to 1800 AD demonstrates how plague epidemics, 1347 to 1670, could have provided the selection pressure that raised the frequency of the mutation to the level seen today. It is suggested that the original single mutation appeared over 2500 years ago and that persistent epidemics of a haemorrhagic fever that struck at the early classical civilisations served to force up the frequency to about 5x10(-5) at the time of the Black Death in 1347.