SARS-CoV-2 mutant spectrum complexity is an epidemiologically evolvable trait
Abstract
RNA virus populations consist of complex and dynamic mutant spectra in which most individual genomes differ in one or more positions from the other genomes of the same population. This behavior, known as quasispecies dynamics, applies to SARS-CoV-2 which exhibits intrahost genetic and functional heterogeneity while evolving at a high rate in the human population. In the present study, we describe a remarkable reduction in mutant spectrum complexity (intrahost viral genome heterogeneity) in SARS-CoV-2 isolates of late relative to early COVID-19 waves, as they reached Madrid (Spain) from 2020 until 2022. In contrast, the consensus (average) sequence of the corresponding isolates displayed a continuing divergence from the initial Wuhan-Hu-1 virus as the pandemic advanced. The mutant spectrum complexity developed upon replication in Vero E6 cells of the isolates from the first and sixth COVID-19 waves, as well as of biological clones retrieved from them, was similar. Therefore, the mutant spectrum complexity reduction observed in vivo was not due to an increased accuracy of the viral replicative machinery, but rather to other factors related to viral epidemiology or pathogenesis. Such possible factors and their implications for viral trait modifications in the course of a viral pandemic are discussed. The results establish that mutant spectrum complexity of genetically variable viruses can be an epidemiologically evolvable trait.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (15)
Brenda Martínez-González
Microbes in Health and Welfare Program, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid)
María Eugenia Soria
Microbes in Health and Welfare Program, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid)
Ana Isabel de Ávila
Microbes in Health and Welfare Program, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid)
Pilar Somovilla
Microbes in Health and Welfare Program, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid)
Claudia Aguilar-Sabido
Management Solutions, Torre Picasso
Pablo Mínguez
Department of Genetics and Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid
Cristina Ferrer-Orta
Structural and Molecular Biology Department, Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas
Llanos Salar-Vidal
Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid
Ramon Lorenzo-Redondo
Soledad Delgado
Departamento de Sistemas Informáticos, Escuela Técnica Superior de Ingeniería de Sistemas Informáticos, Universidad Politécnica de Madrid
Federico Morán
Departamento de Bioquímica y Biología Molecular, Universidad Complutense de Madrid
Nuria Verdaguer
Structural and Molecular Biology Department, Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas
Ignacio Gadea
Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid
Esteban Domingo
Microbes in Health and Welfare Program, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid)
Celia Perales
Microbes in Health and Welfare Program, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid)