Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient
Gregori i Font, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Colomer-Castell, Sergi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Campos, Carolina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ibañez-Lligoña, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia-Cehic, D. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rando-Segura, Ariadna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Adombie, Caroline Melanie (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pintó, Rosa (Universitat de Barcelona)
Guix, Susana (Universitat de Barcelona)
Bosch, Albert (Universitat de Barcelona)
Domingo, Esteban (Instituto de Salud Carlos III)
Gallego, Isabel (Centro de Biología Molecular Severo Ochoa)
Perales Viejo, Celia (Universidad Autónoma de Madrid)
Cortese, Maria Francesca (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tabernero, David (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Buti, Maria (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Riveiro Barciela, Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Esteban Mur, Juan Ignacio (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez Frías, Francisco (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Quer, Josep 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	The changes occurring in viral quasispecies populations during infection have been monitored using diversity indices, nucleotide diversity, and several other indices to summarize the quasispecies structure in a single value. In this study, we present a method to partition quasispecies haplotypes into four fractions according to their fitness: the master haplotype, rare haplotypes at two levels (those present at <0. 1%, and those at 0. 1-1%), and a fourth fraction that we term emerging haplotypes, present at frequencies >1%, but less than that of the master haplotype. We propose that by determining the changes occurring in the volume of the four quasispecies fitness fractions together with those of the Hill number profile we will be able to visualize and analyze the molecular changes in the composition of a quasispecies with time. To develop this concept, we used three data sets: a technical clone of the complete SARS-CoV-2 spike gene, a subset of data previously used in a study of rare haplotypes, and data from a clinical follow-up study of a patient chronically infected with HEV and treated with ribavirin. The viral response to ribavirin mutagenic treatment was selection of a rich set of synonymous haplotypes. The mutation spectrum was very complex at the nucleotide level, but at the protein (phenotypic/functional) level the pattern differed, showing a highly prevalent master phenotype. We discuss the putative implications of this observation in relation to mutagenic antiviral treatment.
Ayudas:	Instituto de Salud Carlos III PI19/00301
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Deep-sequencing ; Fitness ; Mutagens ; Quasispecies ; Rare haplotypes ; Variability
Publicado en:	International journal of molecular sciences, Vol. 23 (november 2022) , ISSN 1422-0067

DOI: 10.3390/ijms232314654
PMID: 36498981

17 p, 2.4 MB

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