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Sequential Turnover of Human Immunodeficiency Virus Type 1 env throughout the Course of Infection ^,

Tara M. Riddle,¹ Norah J. Shire,² Marc S. Sherman,² Kelly F. Franco,^1, Haynes W. Sheppard,³ and Julie A. E. Nelson^1*

Department of Molecular Genetics, Biochemistry and Microbiology,¹ Department of Medicine, University of Cincinnati, Cincinnati, Ohio,² California Department of Health Services, Richmond, California³

Received 30 March 2006/ Accepted 21 August 2006

We examined the rates of variant population turnover of the V1-V2 and V4-V5 hypervariable domains of the human immunodeficiency virus type 1 (HIV-1) gp120 molecule in longitudinal plasma samples from 14 men with chronic HIV-1 infection using heteroduplex tracking assays (HTA). Six men had high rates of CD4⁺ T-cell loss, and eight men had low rates of CD4⁺ T-cell loss over 2.5 to 8 years of infection. We found that V1-V2 and V4-V5 env populations changed dramatically over time in all 14 subjects; the changes in these regions were significantly correlated with each another over time. The subjects with rapid CD4 loss had significantly less change in their env populations than the subjects with slow CD4 loss. The two subjects with rapid CD4 loss and sustained low CD4 counts (<150/µl for at least 2 years) showed stabilization of their V1-V2 and V4-V5 populations as reflected by low levels of total change in HTA pattern and low HTA indices (a novel measure of the emergence of new bands and band distribution); this stabilization was not observed in other subjects. The stabilization of env variant populations at low CD4 counts following periods of rapid viral evolution suggests that selective pressure on env, likely from new immune responses, is minimal when CD4 counts drop dramatically and remain low for extended periods of time.

Published ahead of print on 6 September 2006.

Supplemental material for this article may be found at http://jvi.asm.org/.

Present address: Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA.

This article has been cited by other articles:

• Harrington, P. R., Nelson, J. A. E., Kitrinos, K. M., Swanstrom, R. (2007). Independent Evolution of Human Immunodeficiency Virus Type 1 env V1/V2 and V4/V5 Hypervariable Regions during Chronic Infection. J. Virol. 81: 5413-5417 [Abstract] [Full Text]