title: A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination.
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.
authors.affiliation: Department of Mathematics, University of Chester, Chester, UK.|Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Gennady
authors.initials: G
authors.lastname: Bocharov
authors.affiliation: Department of Mathematics, University of Chester, Chester, UK.
authors.forename: Neville J
authors.initials: NJ
authors.lastname: Ford
authors.affiliation: Department of Mathematics, University of Chester, Chester, UK.
authors.forename: John
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Department of Virology, University of the Saarland, Homburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Breinig
authors.affiliation: Unité de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
authors.affiliation: Department of Virology, University of the Saarland, Homburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D019143:Evolution, Molecular; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D017354:Point Mutation; D011995:Recombination, Genetic