The Journal of Experimental Medicine
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J. Exp. Med., Volume 188, Number 11, December 7, 1998 2057-2065

Natural Infection of a Homozygous Delta 24 CCR5 Red-capped Mangabey with an R2b-Tropic Simian Immunodeficiency Virus

By Zhiwei Chen,* Douglas Kwon,* Zhanqun Jin,* Simon Monard,* Paul Telfer,*Dagger Morris S. Jones,*§ Chang Y. Lu,parallel Roberto F. Aguilar, David D. Ho,* and Preston A. Marx***

From the * Aaron Diamond AIDS Research Center, The Rockefeller University, New York 10016; the Dagger  Department of Anthropology and the § Department of Microbiology, New York University Medical Center, New York 10016; parallel  Centre International de Recherches Medicales, Franceville, Gabon; the  Audubon Park Zoo, New Orleans, Louisiana 70118; and the ** Department of  Tropical Medicine and Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, Louisiana 70433

A homozygous 24-bp deletion (Delta 24) was found in the CC chemokine receptor 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquatus torquatus, both in Africa and in an American zoo. The CCR5 Delta 24 defect encompassed eight amino acids in frame in the fourth transmembrane region. Unexpectedly, RCM-009, one of 11 homozygotes (Delta 24CCR5/ Delta 24CCR5), was found to be naturally infected with a divergent simian immunodeficiency virus (SIV) strain, which was not R5-tropic, but used CCR2b (R2b) as its major coreceptor. SIVrcmGab1 was the only R2b-tropic SIV among other divergent 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 mangabeys (SMs), a geographically isolated subspecies that was naturally infected with R5-tropic SIV. Finding identical deletions in two mangabey subspecies separated for 10,000 years or more dates the Delta 24 CCR5 deletion as ancient. However, the source of the selective pressure for the high rate of CCR5 deletion in RCMs remains to be determined. The high allelic frequency of the Delta 24 CCR5 in RCMs, in comparison to that of SMs, suggests that R2b-tropism may have been acquired by SIVrcm, as an adaptation to CCR5 genetic defects appeared in its host.

Key words: SIVrcm;  CCR5;  CCR2b;  mangabey;  Delta 24 defect


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