Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/72377
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Type: Journal article
Title: The dynamics of HIV-1 adaptation in early infection
Author: Da Silva, J.
Citation: Genetics, 2012; 190(3):1087-1099
Publisher: Genetics
Issue Date: 2012
ISSN: 0016-6731
1943-2631
Statement of
Responsibility: 
Jack da Silva
Abstract: Human immunodeficiency virus type 1 (HIV-1) undergoes a severe population bottleneck during sexual transmission and yet adapts extremely rapidly to the earliest immune responses. The bottleneck has been inferred to typically consist of a single genome, and typically eight amino acid mutations in viral proteins spread to fixation by the end of the early chronic phase of infection in response to selection by CD8+ T cells. Stochastic simulation was used to examine the effects of the transmission bottleneck and of potential interference among spreading immune-escape mutations on the adaptive dynamics of the virus in early infection. If major viral population genetic parameters are assigned realistic values that permit rapid adaptive evolution, then a bottleneck of a single genome is not inconsistent with the observed pattern of adaptive fixations. One requirement is strong selection by CD8+ T cells that decreases over time. Such selection may reduce effective population sizes at linked loci through genetic hitchhiking. However, this effect is predicted to be minor in early infection because the transmission bottleneck reduces the effective population size to such an extent that the resulting strong selection and weak mutation cause beneficial mutations to fix sequentially and thus avoid interference.
Keywords: Humans; HIV-1; HIV Infections; Adaptation, Biological; Evolution, Molecular; Algorithms; Models, Biological; Computer Simulation; Selection, Genetic
Rights: Copyright © 2012 by the Genetics Society of America
RMID: 0020117431
DOI: 10.1534/genetics.111.136366
Appears in Collections:Molecular and Biomedical Science publications

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