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

Published

Journal Article

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.

Full Text

Cited Authors

  • Ross, HA; Rodrigo, AG

Published Date

  • November 2002

Published In

Volume / Issue

  • 76 / 22

Start / End Page

  • 11715 - 11720

PubMed ID

  • 12388731

Pubmed Central ID

  • 12388731

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/JVI.76.22.11715-11720.2002

Language

  • eng