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Journal of Virology, October 2005, p. 12296-12303, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12296-12303.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

V3 Loop-Determined Coreceptor Preference Dictates the Dynamics of CD4+-T-Cell Loss in Simian-Human Immunodeficiency Virus-Infected Macaques

Siu-hong Ho,1 Lili Shek,1 Agegnehu Gettie,1 James Blanchard,2 and Cecilia Cheng-Mayer1*

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 27 May 2005/ Accepted 6 July 2005

We used experimental infection of rhesus macaques with envelope gp120 V3 loop isogenic simian-human immunodeficiency virus (SHIV) molecular clones to more clearly define the impact of human immunodeficiency virus type 1 coreceptor usage in target cell selectivity and the rates of CD4+-T-cell depletion. Functional assays demonstrate that substitution of the V3 loop of the pathogenic CXCR4-tropic (X4) SHIVSF33A2 molecular clone with the corresponding sequences from the CCR5-tropic (R5) SHIVSF162P3 isolate resulted in a switch of coreceptor usage from CXCR4 to CCR5. The resultant R5 clone, designated SHIVSF33A2(V3), is replication competent in vivo, infecting two of two macaques by intravenous inoculation with peak viremia that is comparable to that seen in monkeys infected with X4-SHIVSF33A2. But while primary infection with the X4 clone was accompanied by rapid and significant loss of peripheral and secondary lymphoid CD4+ T lymphocytes, infection with R5-SHIVSF33A2(V3) led to only a modest and transient loss. However, substantial depletion of intestinal CD4+ T cells was observed in R5-SHIVSF33A2(V3)-infected macaques. Moreover, naïve T cells that expressed high levels of CXCR4 were rapidly depleted in X4-SHIVSF33A2-infected macaques, whereas R5-SHIVSF33A2(V3) infection mainly affected memory T cells that expressed CCR5. These findings in a unique isogenic system illustrate that coreceptor usage is the principal determinant of tissue and target cell specificity of the virus in vivo and dictates the dynamics of CD4+-T-cell depletion during SHIV infection.

* Corresponding author. Mailing address: Rockefeller University, Aaron Diamond AIDS Research Center, 455 First Ave., 7th Floor, New York, NY 10016. Phone: (212) 448-5080. Fax: (212) 448-5158. E-mail: cmayer{at}adarc.org.

Journal of Virology, October 2005, p. 12296-12303, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12296-12303.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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]  
  • Ho, S.-h., Tasca, S., Shek, L., Li, A., Gettie, A., Blanchard, J., Boden, D., Cheng-Mayer, C. (2007). Coreceptor Switch in R5-Tropic Simian/Human Immunodeficiency Virus-Infected Macaques. J. Virol. 81: 8621-8633 [Abstract] [Full Text]  


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