Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient
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Published:2022-11-24
Issue:23
Volume:23
Page:14654
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Gregori JosepORCID,
Colomer-Castell Sergi,
Campos Carolina,
Ibañez-Lligoña MartaORCID,
Garcia-Cehic Damir,
Rando-Segura AriadnaORCID,
Adombie Caroline Melanie,
Pintó Rosa,
Guix SusannaORCID,
Bosch AlbertORCID,
Domingo Esteban,
Gallego Isabel,
Perales CeliaORCID,
Cortese Maria FrancescaORCID,
Tabernero David,
Buti Maria,
Riveiro-Barciela MarORCID,
Esteban Juan Ignacio,
Rodriguez-Frias FranciscoORCID,
Quer JosepORCID
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.
Funder
Plan Estratègic de Recerca i Innovació en Salut
—Direcció General de Recerca i Innovació en Salut
Catalan Health Ministry
Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business
European Regional Development Fund
Gilead’s biomedical research project
Ministerio de Ciencia e Innovación
Comunidad de Madrid/FEDER
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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