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Journal of Virology, May 2009, p. 4068-4080, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02486-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Major Coexisting Human Immunodeficiency Virus Type 1 env Gene Subpopulations in the Peripheral Blood Are Produced by Cells with Similar Turnover Rates and Show Little Evidence of Genetic Compartmentalization{triangledown}

William L. Ince,1 Patrick R. Harrington,2 Gretja L. Schnell,2 Milloni Patel-Chhabra,2 Christina L. Burch,3 Prema Menezes,4 Richard W. Price,5 Joseph J. Eron Jr.,4 and Ronald I. Swanstrom1,2,4*

Curriculum in Genetics and Molecular Biology,1 Department of Microbiology and Immunology,2 Department of Biology,3 UNC Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina 27599,4 Department of Neurology, University of California, San Francisco, California 941435

Received 3 December 2008/ Accepted 3 February 2009

A distinctive feature of chronic human immunodeficiency virus type 1 (HIV-1) infection is the presence of multiple coexisting genetic variants, or subpopulations, that comprise the HIV-1 population detected in the peripheral blood. Analysis of HIV-1 RNA decay dynamics during the initiation of highly active antiretroviral therapy (HAART) has been a valuable tool for modeling the life span of infected cells that produce the bulk HIV-1 population. However, different HIV-1 target cells may have different turnover rates, and it is not clear whether the bulk HIV-1 RNA decay rate actually represents a composite of the decay rates of viral subpopulations compartmentalized in different cellular subsets with different life spans. Using heteroduplex tracking assays targeting the highly variable V3 or V4-V5 regions of the HIV-1 env gene in eight subjects, we found that all detectable coexisting HIV-1 variants in the peripheral blood generally decayed at similar rates during the initiation of HAART, suggesting that all of the variants were produced by cells with similar life spans. Furthermore, single genome amplification and coreceptor phenotyping revealed that in two subjects coexisting HIV-1 variants with distinct CXCR4 or CCR5 coreceptor phenotypes decayed with similar rates. Also, in nine additional subjects, recombination and a lack of genetic compartmentalization between X4 and R5 variants were observed, suggesting an overlap in host cell range. Our results suggest that the HIV-1 env subpopulations detectable in the peripheral blood are produced by cells with similar life spans and are not genetically isolated within particular cell types.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB #7295, Chapel Hill, NC 27599-7295. Phone: (919) 966 5710. Fax: (919) 966 8212. E-mail: risunc{at}med.unc.edu

{triangledown} Published ahead of print on 11 February 2009.

Journal of Virology, May 2009, p. 4068-4080, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02486-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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