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Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient.

Authors :
Gregori, Josep
Colomer-Castell, Sergi
Campos, Carolina
Ibañez-Lligoña, Marta
Garcia-Cehic, Damir
Rando-Segura, Ariadna
Adombie, Caroline Melanie
Pintó, Rosa
Guix, Susanna
Bosch, Albert
Domingo, Esteban
Gallego, Isabel
Perales, Celia
Cortese, Maria Francesca
Tabernero, David
Buti, Maria
Riveiro-Barciela, Mar
Esteban, Juan Ignacio
Rodriguez-Frias, Francisco
Quer, Josep
Source :
International Journal of Molecular Sciences. Dec2022, Vol. 23 Issue 23, p14654. 17p.
Publication Year :
2022

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
23
Issue :
23
Database :
Academic Search Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
160740346
Full Text :
https://doi.org/10.3390/ijms232314654