A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination

Hdl Handle:
http://hdl.handle.net/10034/67761
Title:
A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination
Authors:
Bocharov, Gennady; Ford, Neville J.; Edwards, John T.; Breinig, Tanja; Wain-Hobson, Simon; Meyerhans, Andreas
Abstract:
It has been previously shown that the majority of human immunodeficiency virus type 1 (HIV-1)-infected splenocytes can harbour multiple, divergent proviruses with a copy number ranging from one to eight. This implies that, besides point mutations, recombination should be considered as an important mechanism in the evolution of HIV within an infected host. To explore in detail the possible contributions of multi-infection and recombination to HIV evolution, the effects of major microscopic parameters of HIV replication (i.e. the point-mutation rate, the crossover number, the recombination rate and the provirus copy number) on macroscopic characteristics (such as the Hamming distance and the abundance of n-point mutants) have been simulated in silico. Simulations predict that multiple provirus copies per infected cell and recombination act in synergy to speed up the development of sequence diversity. Point mutations can be fixed for some time without fitness selection. The time needed for the selection of multiple mutations with increased fitness is highly variable, supporting the view that stochastic processes may contribute substantially to the kinetics of HIV variation in vivo.
Affiliation:
Institute of Numerical Mathematics, Russian Academy of Sciences ; University of Chester ; University of Chester ; University of the Saarland ; Unité de Rétrovirologie Moléculaire, Institut Pasteur ; University of the Saarland
Citation:
Journal of General Virology, 86, 2005, pp. 3109-3118
Publisher:
Society for General Microbiology / High Wire Press
Journal:
Journal of General Virology
Publication Date:
2005
URI:
http://hdl.handle.net/10034/67761
DOI:
10.1099/vir.0.81138-0
Additional Links:
http://vir.sgmjournals.org
Type:
Article
Language:
en
Description:
This article is not available through ChesterRep.
ISSN:
0022-1317; 1465-2099
Sponsors:
This article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.
Appears in Collections:
Mathematics

Full metadata record

DC FieldValue Language
dc.contributor.authorBocharov, Gennadyen
dc.contributor.authorFord, Neville J.en
dc.contributor.authorEdwards, John T.en
dc.contributor.authorBreinig, Tanjaen
dc.contributor.authorWain-Hobson, Simonen
dc.contributor.authorMeyerhans, Andreasen
dc.date.accessioned2009-05-11T11:22:16Zen
dc.date.available2009-05-11T11:22:16Zen
dc.date.issued2005en
dc.identifier.citationJournal of General Virology, 86, 2005, pp. 3109-3118en
dc.identifier.issn0022-1317en
dc.identifier.issn1465-2099en
dc.identifier.doi10.1099/vir.0.81138-0en
dc.identifier.urihttp://hdl.handle.net/10034/67761en
dc.descriptionThis article is not available through ChesterRep.en
dc.description.abstractIt has been previously shown that the majority of human immunodeficiency virus type 1 (HIV-1)-infected splenocytes can harbour multiple, divergent proviruses with a copy number ranging from one to eight. This implies that, besides point mutations, recombination should be considered as an important mechanism in the evolution of HIV within an infected host. To explore in detail the possible contributions of multi-infection and recombination to HIV evolution, the effects of major microscopic parameters of HIV replication (i.e. the point-mutation rate, the crossover number, the recombination rate and the provirus copy number) on macroscopic characteristics (such as the Hamming distance and the abundance of n-point mutants) have been simulated in silico. Simulations predict that multiple provirus copies per infected cell and recombination act in synergy to speed up the development of sequence diversity. Point mutations can be fixed for some time without fitness selection. The time needed for the selection of multiple mutations with increased fitness is highly variable, supporting the view that stochastic processes may contribute substantially to the kinetics of HIV variation in vivo.en
dc.description.sponsorshipThis article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.en
dc.language.isoenen
dc.publisherSociety for General Microbiology / High Wire Pressen
dc.relation.urlhttp://vir.sgmjournals.orgen
dc.subjectHIV virusen
dc.titleA genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombinationen
dc.typeArticleen
dc.contributor.departmentInstitute of Numerical Mathematics, Russian Academy of Sciences ; University of Chester ; University of Chester ; University of the Saarland ; Unité de Rétrovirologie Moléculaire, Institut Pasteur ; University of the Saarlanden
dc.identifier.journalJournal of General Virologyen
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