Molecular evolution and antigenic mapping of classical swine fever virus: a comprehensive analysis of E2 genomic variability and selection dynamics.

Worldwide, the pig industry suffers financial losses due to the extremely contagious disease caused by the classical swine fever virus (CSFV). However, comprehensive and global genotyping information for CSFV remains scarce. A total of 1,053 full length E2 sequences of CSFV from the NCBI database were used in this study. According to phylogenetic analysis, the strains were grouped into dominant genetic subgroups. The positive selection pressures on the CSFV E2 envelope protein genes were also evaluated and a site-by-site examination of the dN/dS ratio was conducted to pinpoint certain codons that diversify under positive selection. Phylogenomic analyses using maximum likelihood (ML) and Bayesian inference (BI) confirmed that the 1,053 strains clustered within the previously defined five subgenotypes (1.1, 1.2, 2.1, 2.3 and 3.4). One positively selected site was identified at amino acid residue position 71. Bayesian coalescent analysis estimated an evolutionary rate of 1.364 × 10⁻³ substitutions per site per year (95% HPD: 1.1808 × 10⁻³-1.5602 × 10⁻³) and a tMRCA of approximately 1816 (95% HPD: 1796-1837). The effective population size of CSFV began increasing in the 1920s, continued to rise until the 1950s, and then remained stable thereafter. Sequence-based antigenic mapping was used to evaluate antigenic relationships among CSFV strains, revealing that most strains clustered closely together. Understanding the molecular epidemiology and functional significance of positively selected amino acid sites may aid in predicting changes in virulence and inform vaccine development and disease control strategies.