Monte Carlo simulation of HIV-1 evolution in response to selection by antibodies

Abstract

The persistence of human immunodeficiency virus type 1 (HIV-1) infection may be in part attributed to its ability to evolve to evade neutralizing antibody (NAb) surveillance. We have tested the prediction that positive selection of V3 is positively correlated with the strength of a patient’s NAb response by analyzing a data set containing both sequences from the principal neutralizing domain of HIV-1 (V3) and measures of the strength of the NAb responses of several patients. Only viral sequences from the patient with the strongest NAb response exhibited evidence of significant positive selection. To investigate the nature of selection by NAbs, we simulated the evolution of V3 at the nucleotide level. Two forms of plausible NAb selection were used: negative frequency-dependent selection and negative viral-age-dependent selection. Assuming negative age-dependent selection rather than negative frequency-dependent selection better simulated the temporal pattern of V3 variation from the patient with the strongest NAb response.