Immune-mediated positive selection drives human immunodeficiency virus type 1 molecular variation and predicts disease duration.
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.
Ross
Howard A
HA
Computational and Evolutionary Biology Laboratory, School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Rodrigo
Allen G
AG
D018450:Disease Progression; D015752:Genes, env / Q000235:genetics; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D010802:Phylogeny; D012641:Selection, Genetic