Improving virus production through quasispecies genomic selection and molecular breedings

• Published in: Scientific reports 2016-11
• Main Authors: Pérez Rodríguez, Francisco Javier, 1964, D'Andrea, Lucia, Castellarnau Serra, Montserrat de, Costafreda Salvany, M. Isabel, Guix Arnau, Susana, Ribes Mora, Enric, Quer, Josep, Gregori Font, Josep, Bosch, Albert, Pintó Solé, Rosa María
• Format: Article
• Language: English
• Subjects: Espècies (Biologia); Species; Virologia; Virology
• ISSN: 2045-2322; 2045-2322

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.