Immune-mediated positive selection drives human immunodeficiency virus type 1 molecular variation and predicts disease duration - PubMed (original) (raw)

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

Howard A Ross et al. J Virol. 2002 Nov.

Abstract

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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Figures

FIG. 1.

FIG. 1.

The location of sites classified as experiencing positive selection in the C2-V5 region of the HIV-1 env gene. Individual sites are color coded when ω is >1 in at least one sample. The proportion of sites with ω > 1 is indicated as red (<0.01), yellow (0.01 to 0.03), green (0.03 to 0.07), light blue (0.07 to 0.15), dark blue (>0.15), or grey (no sequence). Sequences are arranged vertically, with one column per sample. Subjects are arranged from left to right in decreasing order of longevity or, for subjects with the same longevity, in decreasing proportion of positively selected sites. Within subjects, samples are arranged from left to right by time of collection. Column headings are color coded to indicate the observed proportion of positively selected sites within the sample or subject. Alignment with external reference sequences and gap balancing (32) created gaps.

FIG. 2.

FIG. 2.

Persistence of positive selection in the two groups of subjects. The proportion of sites under positive selection in both of two samples, in all pair-wise comparisons, is plotted against the time interval between samples. The results for each subject are plotted separately. The plots are labeled with the patient identifier and the slope of the line of best fit.

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