A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination
Authors
Bocharov, GennadyFord, Neville J.
Edwards, John T.
Breinig, Tanja
Wain-Hobson, Simon
Meyerhans, Andreas
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 SaarlandPublication Date
2005-11-01
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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.Citation
Journal of General Virology, 86, 2005, pp. 3109-3118Journal
Journal of General VirologyAdditional Links
http://vir.sgmjournals.orgType
ArticleLanguage
enDescription
This article is not available through ChesterRep.ISSN
0022-13171465-2099
Sponsors
This article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.ae974a485f413a2113503eed53cd6c53
10.1099/vir.0.81138-0