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Journal of Virology, November 2002, p. 11715-11720, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11715-11720.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Immune-Mediated Positive Selection Drives Human Immunodeficiency Virus Type 1 Molecular Variation and Predicts Disease Duration

Computational and Evolutionary Biology Laboratory, School of Biological Sciences, University of Auckland, Auckland, New Zealand

Received 9 April 2002/ Accepted 15 August 2002

Using likelihood-based evolutionary methods, we demonstrate that the broad genetic diversity of human immunodeficiency virus type 1 (HIV-1) in an infected individual is a consequence of site-specific positive selection for diversity, a likely consequence of immune recognition. In particular, the extent of positive selection appears to be a good predictor of disease duration. Positively selected sites along HIV-1 partial env sequences are numerous but not distributed uniformly. In a sample of eight patients studied longitudinally, the proportion of sites per sample under positive selection was a statistically significant predictor of disease duration. Among long-term progressors, positive selection persisted at sites over time and appears to be associated with helper T-cell epitopes. In contrast, sites under positive selection shifted from one longitudinal sample to the next in short-term progressors. Our study is consistent with the hypothesis that a broad and persistent immunologic response is associated with a slower rate of disease progression. In contrast, narrow, shifting immune responses characterize short-term progressors.

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