TY - JOUR T1 - An Evolutionary-Network Model Reveals Stratified Interactions in the V3 Loop of the HIV-1 Envelope A1 - Poon, Art F. Y A1 - Lewis, Fraser I A1 - Pond, Sergei L. Kosakovsky A1 - Frost, Simon D. W Y1 - 2007/11/23 N2 - Author SummaryThe third variable loop (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope is a principal determinant of viral growth characteristics and an important target for the immune system. Interactions between residues of V3 allow the virus to shift between combinations of residues to escape the immune system while retaining its structure and functions. Comparative study of HIV-1 V3 sequences can detect such interactions by the covariation of sites in the sequence, which can then be used to inform vaccine development, but current methods for detecting such associations rely on biologically unrealistic assumptions. We demonstrate that these assumptions cause an excessive number of spurious associations, and present a new approach that couples phylogenetic and Bayesian network models, and greatly reduces this number while retaining the ability to detect real associations. Our analysis reveals that the V3 loop is stratified into discrete layers of interacting residues, suggesting a partition of functions along this viral structure with implications for vaccine development. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 3 IS - 11 UR - https://doi.org/10.1371/journal.pcbi.0030231 SP - e231 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.0030231 ER -