Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17443
Título
Influence of mutation and recombination on HIV-1 in vitro fitness recovery
Autor(es)
Fecha de publicación
2016-01
Cita
Mol Phylogenet Evol. 2016 Jan;94(Pt A):264-70.
Idioma
Inglés
Tipo de documento
research article
Resumen
The understanding of the evolutionary processes underlying HIV-1 fitness recovery is fundamental for HIV-1 pathogenesis, antiretroviral treatment and vaccine design. It is known that HIV-1 can present very high mutation and recombination rates, however the specific contribution of these evolutionary forces in the "in vitro" viral fitness recovery has not been simultaneously quantified. To this aim, we analyzed substitution, recombination and molecular adaptation rates in a variety of HIV-1 biological clones derived from a viral isolate after severe population bottlenecks and a number of large population cell culture passages. These clones presented an overall but uneven fitness gain, mean of 3-fold, respect to the initial passage values. We found a significant relationship between the fitness increase and the appearance and fixation of mutations. In addition, these fixed mutations presented molecular signatures of positive selection through the accumulation of non-synonymous substitutions. Interestingly, viral recombination correlated with fitness recovery in most of studied viral quasispecies. The genetic diversity generated by these evolutionary processes was positively correlated with the viral fitness. We conclude that HIV-1 fitness recovery can be derived from the genetic heterogeneity generated through both mutation and recombination, and under diversifying molecular adaptation. The findings also suggest nonrandom evolutionary pathways for in vitro fitness recovery.
Palabras clave
HIV-1 molecular evolution | Mutation | Viral recombination | Molecular 40 adaptation | Genetic heterogeneity | Fitness recovery
MESH
Genetic Fitness | Adaptation, Biological | Evolution, Molecular | HIV Infections | HIV-1 | Humans | Mutation | Phylogeny | Recombination, Genetic
Versión en línea
DOI
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