SARS-CoV-2 mutant spectrum complexity is an epidemiologically evolvable trait

• 成果类型: Article
• 署名作者: Gonzalez, Brenda Martinez-; Soria, Maria Eugenia; Avila, Ana Isabel de; Somovilla, Pilar; Sabido, Claudia Aguilar-; Minguez, Pablo; Orta, Cristina Ferrer-; Vidal, Llanos Salar-; Lorenzo-Redondojk, Ramon; Delgado, Soledad; Moran, Federico; Verdaguer, Nuria; Gadea, Ignacio; Domingo, Esteban; Perales, Celia
• 署名单位: Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Biologia Molecular Severo Ochoa (CBM); Autonomous University of Madrid; Autonomous University of Madrid; Autonomous University of Madrid; Autonomous University of Madrid; Instituto de Salud Carlos III; CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Autonomous University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Biologia Molecular de Barcelona (IBMB); Instituto de Salud Carlos III; Northwestern University; Feinberg School of Medicine; Northwestern University; Universidad Politecnica de Madrid; Complutense University of Madrid
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14240
• DOI: 10.1073/pnas.2515706122
• 发表日期: 2025-09-30
• 关键词: antigenic variation; EVOLUTION; virus; accurate; MODEL

摘要

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.