TY - JOUR
T1 - Improving virus production through quasispecies genomic selection and molecular breeding
AU - Pérez-Rodríguez, Francisco J.
AU - D'Andrea, Luciá
AU - De Castellarnau, Montserrat
AU - Costafreda, Maria Isabel
AU - Guix, Susana
AU - Ribes, Enric
AU - Quer, Josep
AU - Gregori, Josep
AU - Bosch, Albert
AU - Pintó, Rosa M.
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/11/3
Y1 - 2016/11/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84994577087&partnerID=8YFLogxK
U2 - 10.1038/srep35962
DO - 10.1038/srep35962
M3 - Article
C2 - 27808108
AN - SCOPUS:84994577087
SN - 2045-2322
VL - 6
JO - SCIENTIFIC REPORTS
JF - SCIENTIFIC REPORTS
M1 - 35962
ER -