Within-Host Fitness and Antigenicity Shift Are Key Factors Influencing the Prevalence of Within-Host Variations in the SARS-CoV-2 <i>S</i> Gene

Within-Host Fitness and Antigenicity Shift Are Key Factors Influencing the Prevalence of Within-Host Variations in the SARS-CoV-2 <i>S</i> Gene

Within-host evolution plays a critical role in shaping the diversity of SARS-CoV-2. However, understanding the primary factors contributing to the prevalence of intra-host single nucleotide variants (iSNVs) in the viral population remains elusive. Here, we conducted a comprehensive analysis of over...

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Bibliographic Details
Main Authors: Binbin Xi, Zhihao Hua, Dawei Jiang, Zixi Chen, Jinfen Wei, Yuhuan Meng, Hongli Du
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Viruses
Subjects:
SARS-CoV-2
iSNVs
prevalence
within-host fitness
antigenicity shift
Online Access:https://www.mdpi.com/1999-4915/17/3/362
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Summary:Within-host evolution plays a critical role in shaping the diversity of SARS-CoV-2. However, understanding the primary factors contributing to the prevalence of intra-host single nucleotide variants (iSNVs) in the viral population remains elusive. Here, we conducted a comprehensive analysis of over 556,000 SARS-CoV-2 sequencing data and prevalence data of different SARS-CoV-2 S protein amino acid mutations to elucidate key factors influencing the prevalence of iSNVs in the SARS-CoV-2 <i>S</i> gene. Within-host diversity analysis revealed the presence of mutational hotspots within the <i>S</i> gene, mainly located in NTD, RBD, TM, and CT domains. Additionally, we generated a single amino acid resolution selection status map of the S protein. We observed a significant variance in within-host fitness among iSNVs in the S protein. The majority of iSNVs exhibited low to no within-host fitness and displayed low alternate allele frequency (AAF), suggesting that they will be eliminated due to the narrow transmission bottleneck of SARS-CoV-2. Notably, iSNVs with moderate AAFs (0.06–0.12) were found to be more prevalent than those with high AAFs. Furthermore, iSNVs with the potential to alter antigenicity were more prevalent. These findings underscore the significance of within-host fitness and antigenicity shift as two key factors influencing the prevalence of iSNVs in the SARS-CoV-2 <i>S</i> gene.
ISSN:1999-4915

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