Synergistic roles of the E2 glycoprotein and 3′ untranslated region in the increased genomic stability of chimeric classical swine fever virus with attenuated phenotypes

The E2 glycoprotein and 3′ untranslated region (UTR) of classical swine fever virus (CSFV) are virulence determinants. To investigate the synergistic roles of E2 and 3′UTR for pathogenicity and genomic stability, a series of chimeric CSFVs were constructed by replacing the E2 gene and/or 3′UTR of virulent CSFV strain Shimen with the corresponding sequence of the lapinized ‘Chinese’ strain (C-strain) using a reverse genetic approach. The in vitro growth characterization and in vivo pathogenicity of the chimeric CSFVs were investigated. Our results demonstrated that the E2 glycoprotein mediates virus cell-to-cell spread and viral particle release and that the 3′UTR regulates viral RNA replication. The CSFV E2 and 3′UTR synergistically modulate infectious virus production, viral genomic stability in vitro, and attenuation in swine. This work contributes to our understanding of the structure and function of the CSFV genome and virus pathogenicity and will be useful for the development of a novel CSF vaccine.