Reader Comments

Post a new comment on this article

The Curious Case of CCR5 delta 24

Posted by pbio on 07 May 2009 at 22:13 GMT

Author: 'Preston A.' 'Marx'
Position: Professor
Institution: Tulane National Primate Research Center
Additional Authors: none
Submitted Date: February 23, 2006
Published Date: February 24, 2006
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

Some insight into the selection, age and frequency of the d32 deletion in human beings may be come from another lesser-known example of the CCR5 deletion not described in "The Case for Selection of the CCR5 d32" [Plos 3:1963-1960, 2005]. Contrary to CCR5 d32's limited boundaries within Europe, the d24 CCR5 deletion is found in non-human primate (Cercocebus torquatus, the red capped mangabey) a native of equatorial Africa residing well outside of Europe (1). Although the delta 24bp deletion in this species has the same physiologic effect as the deletion in human beings, striking differences exist. The allelic frequency is over 80% in this species (contrasted with d32 at 5-14%). The most striking evidence of strong selection in this case comes from the virus rather than the host. The T cell tropic simian immunodeficiency virus (SIV) that naturally infects the RCM exclusively uses CCR2 (1,2). All other SIVs use CCR5. Therefore, such deletions in CCR5 may not represent a panacea for the AIDS epidemic because this SIV successfully evaded oblivion by changing its co-receptor in its host species. A jump in co-receptors may also have relevance to HIV therapies that blockade CCR5 use.

Regarding the age of the d24 deletion, it must be >10,000 years old because it is found at low frequency in a related species (C. atys) which differentiated from RCMs across boundaries older than 10,000 years.

The question emerges as to whether or not there is strong selection in the host for this deletion. The RCMs 80% allelic frequency may be a bottleneck in this species or represent strong selection for this gene in equatorial Africa. The existence of parallel evolution of CCR5 deletions on 2 continents further raises the question of what common factor selected for CCR5 gene deletions in northern Europe and equatorial Africa at about the same time.

1. 1998 Chen Z., D. Kwon, Z. Jin, S. Monard, P. Telfer, M.S. Jones, R. Aguilar, D.D. Ho, and P.A. Marx. Natural infection of a homozygous ¿¿24 CCR5 red-capped mangabey with an R2b-tropic SIV. Journal of Experimental Medicine, 199:2057-2065.

2. 2000 Zhang, Y-J, B. Lou, R.B. lal, A. Gettie, P.A. Marx and J.P. Moore. The use of inhibitors to evaluate co-receptor usage by simian and simian/human immunodeficiency viruses and human immunodeficiency virus type 2 in primary cells. Journal of Virology, 74:6893-6910.

Competing interests declared: I declare that I have no competing interests.