Immune-mediated positive selection drives human immunodeficiency virus type 1 molecular variation and predicts disease duration

被引:100
作者
Ross, HA [1 ]
Rodrigo, AG [1 ]
机构
[1] Univ Auckland, Sch Biol Sci, Computat & Evolutionary Biol Lab, Auckland 1, New Zealand
关键词
D O I
10.1128/JVI.76.22.11715-11720.2002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Using likelihood-based evolutionary methods, we demonstrate that the broad genetic diversity of human immunodeficiency virus type I (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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收藏
页码:11715 / 11720
页数:6
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