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Improving virus production through quasispecies genomic selection and molecular breeding.


ABSTRACT: Virus production still is a challenging issue in antigen manufacture, particularly with slow-growing viruses. Deep-sequencing of genomic regions indicative of efficient replication may be used to identify high-fitness minority individuals suppressed by the ensemble of mutants in a virus quasispecies. Molecular breeding of quasispecies containing colonizer individuals, under regimes allowing more than one replicative cycle, is a strategy to select the fittest competitors among the colonizers. A slow-growing cell culture-adapted hepatitis A virus strain was employed as a model for this strategy. Using genomic selection in two regions predictive of efficient translation, the internal ribosome entry site and the VP1-coding region, high-fitness minority colonizer individuals were identified in a population adapted to conditions of artificially-induced cellular transcription shut-off. Molecular breeding of this population with a second one, also adapted to transcription shut-off and showing an overall colonizer phenotype, allowed the selection of a fast-growing population of great biotechnological potential.

SUBMITTER: Perez-Rodriguez FJ 

PROVIDER: S-EPMC5093897 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Improving virus production through quasispecies genomic selection and molecular breeding.

Pérez-Rodríguez Francisco J FJ   D'Andrea Lucía L   de Castellarnau Montserrat M   Costafreda Maria Isabel MI   Guix Susana S   Ribes Enric E   Quer Josep J   Gregori Josep J   Bosch Albert A   Pintó Rosa M RM  

Scientific reports 20161103


Virus production still is a challenging issue in antigen manufacture, particularly with slow-growing viruses. Deep-sequencing of genomic regions indicative of efficient replication may be used to identify high-fitness minority individuals suppressed by the ensemble of mutants in a virus quasispecies. Molecular breeding of quasispecies containing colonizer individuals, under regimes allowing more than one replicative cycle, is a strategy to select the fittest competitors among the colonizers. A s  ...[more]

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