The discovery of the 32-bp deletion allele of the chemokine receptor gene
CCR5
showed that homozygous carriers display near-complete resistance to HIV infection, irrespective of exposure. Algorithms of molecular evolutionary theory suggested that the
CCR5-
∆
32
mutation occurred but once in the last millennium and rose by strong selective pressure relatively recently to a ~10% allele frequency in Europeans. Several lines of evidence support the hypothesis that
CCR5-
∆
32
was selected due to its protective influence to resist
Yersinia pestis,
the agent of the Black Death/bubonic plague of the 14th century. Powerful anti-AIDS entry inhibitors targeting CCR5 were developed as a treatment for HIV patients, particularly those whose systems had developed resistance to powerful anti-retroviral therapies. Homozygous
CCR5-
∆
32/
∆
32
stem cell transplant donors were used to produce HIV-cleared AIDS patients in at least five “cures” of HIV infection. CCR5 has also been implicated in regulating infection with
Staphylococcus aureus
, in recovery from stroke, and in ablation of the fatal graft versus host disease (GVHD) in cancer transplant patients. While homozygous
CCR5-
∆
32/32
carriers block HIV infection, alternatively they display an increased risk for encephalomyelitis and death when infected with the West Nile virus.