Natural infection of a homozygous Delta 24 CCR5 red-capped mangabey with an R2b-tropic simian immunodeficiency virus

A homozygous 24-bp deletion (Delta 24) was found in die CC chemokine recept or 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquat us torquatus, both in Africa and in an American zoo. The CCR5 Delta 24 defe ct encompassed eight amino acids in frame in the fourth transmembrane regio n. Unexpectedly, RCM-009, one of 11 homozygotes (Delta 24CCR5/ Delta 24CCR5 ), was found to be naturally infected with a divergent simian immunodeficie ncy virus (SIV) strain, which was not R5-tropic, but used CCR2b (R2b) as it s major coreceptor. SIVrcmGab1 was the only R2b-tropic SIV among other dive rgent SIVs tested. Cells transfected with the Delta 24 CCR5 did not support entry of R5-tropic SIVmac, SIVcpz, SIVmne, HIV-2, or HIV-1, and were also inactive in signal transduction mediated by beta-chemokines. At 86.6%, the Delta 24 allelic frequency was significantly higher than that of the 32-bp deletion found in humans. The Delta 24 frequency was 4.1% in 34 sooty manga beys (SMs), a geographically isolated subspecies that was naturally infecte d with R5-tropic SIV. Finding identical deletions in two mangabey subspecie s separated for 10,000 years or more dates the Delta 24 CCR5 deletion as an cient. However, the source of the selective pressure for the high rate of C CR5 deletion in RCMs remains to be determined. The high allelic frequency o f the Delta 24 CCR5 in RCMs, in comparison to that of SMs, suggests that R2 b-tropism may have been acquired by SIVrcm, as an adaptation to CCR5 geneti c defects appeared in its host.