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  Estimating the mutational fitness effects distribution during early HIV infection

Bons, E., Bertels, F., & Regoes, R. R. (2018). Estimating the mutational fitness effects distribution during early HIV infection. Virus Evolution, 4(2): vey029. doi:10.1093/ve/vey029.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-64E3-D Version Permalink: http://hdl.handle.net/21.11116/0000-0002-6678-5
Genre: Journal Article

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 Creators:
Bons, Eva, Author
Bertels, Frederic1, Author              
Regoes, Roland R, Author
Affiliations:
1Research Group Microbial Molecular Evolution, Department Microbial Population Biology, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2497692              

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Free keywords: HIV, fitness effects distribution, primary infection, computational model, ABC-SMC
 Abstract: The evolution of HIV during acute infection is often considered a neutral process. Recent analysis of sequencing data from this stage of infection, however, showed high levels of shared mutations between independent viral populations. This suggests that selection might play a role in the early stages of HIV infection. We adapted an existing model for random evolution during acute HIV-infection to include selection. Simulations of this model were used to fit a global mutational fitness effects distribution to previously published sequencing data of the env gene of individuals with acute HIV infection. Measures of sharing between viral populations were used as summary statistics to compare the data to the simulations. We confirm that evolution during acute infection is significantly different from neutral. The distribution of mutational fitness effects is best fit by a distribution with a low, but significant fraction of beneficial mutations and a high fraction of deleterious mutations. While most mutations are neutral or deleterious in this model, about 5% of mutations are beneficial. These beneficial mutations will, on average, result in a small but significant increase in fitness. When assuming no epistasis, this indicates that, at the moment of transmission, HIV is near, but not on the fitness peak for early infection.

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Language(s): eng - English
 Dates: 2018-10-042018-07-01
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1093/ve/vey029
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Project name : Swiss National Science Foundation
Grant ID : 31003A_149769
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Title: Virus Evolution
Source Genre: Journal
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Publ. Info: UK : Oxford University Press
Pages: - Volume / Issue: 4 (2) Sequence Number: vey029 Start / End Page: - Identifier: Other: 2057-1577
CoNE: https://pure.mpg.de/cone/journals/resource/2057-1577