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Coreceptor Switch in R5-Tropic Simian/Human Immunodeficiency Virus-Infected Macaques

Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., 7th Floor, New York, New York 10016,¹ Tulane National Primate Research Center, Tulane University Medical Center, 18702 Three Rivers Road, Covington, Louisiana 70433²

Received 9 April 2007/ Accepted 17 May 2007

The basis for the switch from CCR5 to CXCR4 coreceptor usage seen in 50% of human immunodeficiency virus type 1 (HIV-1) subtype B-infected individuals as disease advances is not well understood. Among the reasons proposed are target cell limitation and better immune recognition of the CXCR4 (X4)-tropic compared to the CCR5 (R5)-tropic virus. We document here X4 virus emergence in a rhesus macaque (RM) infected with R5-tropic simian/human immunodeficiency virus, demonstrating that coreceptor switch can happen in a nonhuman primate model of HIV/AIDS. The switch to CXCR4 usage in RM requires envelope sequence changes in the V3 loop that are similar to those found in humans, suggesting that the R5-to-X4 evolution pathways in the two hosts overlap. Interestingly, compared to the inoculating R5 virus, the emerging CXCR4-using virus is highly neutralization sensitive. This finding, coupled with the observation of X4 evolution and appearance in an animal with undetectable circulating virus-specific antibody and low cellular immune responses, lends further support to an inhibitory role of antiviral immunity in HIV-1 coreceptor switch.

Published ahead of print on 30 May 2007.

This article has been cited by other articles:

• Tasca, S., Ho, S.-H., Cheng-Mayer, C. (2008). R5X4 Viruses Are Evolutionary, Functional, and Antigenic Intermediates in the Pathway of a Simian-Human Immunodeficiency Virus Coreceptor Switch. J. Virol. 82: 7089-7099 [Abstract] [Full Text]  
• Ho, S.-h., Trunova, N., Gettie, A., Blanchard, J., Cheng-Mayer, C. (2008). Different Mutational Pathways to CXCR4 Coreceptor Switch of CCR5-Using Simian-Human Immunodeficiency Virus. J. Virol. 82: 5653-5656 [Abstract] [Full Text]