Quantifying In-Host Quasispecies Evolution

Abstract

Mutagenesis; Quasispecies evolution; Viral treatment

Mutagénesis; Evolución de las cuasiespecies; Tratamiento viral

Mutagènesi; Evolució de les quasiespècies; Tractament viral

What takes decades, centuries or millennia to happen with a natural ecosystem, it takes only days, weeks or months with a replicating viral quasispecies in a host, especially when under treatment. Some methods to quantify the evolution of a quasispecies are introduced and discussed, along with simple simulated examples to help in the interpretation and understanding of the results. The proposed methods treat the molecules in a quasispecies as individuals of competing species in an ecosystem, where the haplotypes are the competing species, and the ecosystem is the quasispecies in a host, and the evolution of the system is quantified by monitoring changes in haplotype frequencies. The correlation between the proposed indices is also discussed, and the R code used to generate the simulations, the data and the plots is provided. The virtues of the proposed indices are finally shown on a clinical case.

This study was partially supported by Pla Estratègic de Recerca i Innovació en Salut (PERIS)—Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; the Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016/0003) from the European Regional Development Fund (ERDF); Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297; grant PI19/00301 and PI22/00258 from Instituto de Salud Carlos III cofinanced by the European Regional Development Fund (ERDF), and Gilead’s biomedical research project GLD21/00006.