Location: Foreign Animal Disease ResearchTitle: Mutations in the Carboxyl Terminal Region of E2 Glycoprotein of Classical Swine Fever Virus are Responsible for Viral Attenuation in Swine) Author
Submitted to: Positive Strand RNA Virus International Conference Proceedings
Publication Type: Abstract only
Publication Acceptance Date: 5/25/2007
Publication Date: 5/26/2007
Citation: Risatti, G.R., Holinka, L.G., Fernanez-Sainz, I., Carrillo, C., Kutish, G., Lu, Z., Zhu, J., Rock, D.L., Borca, M.V., 2007, Mutations in the Carboxyl Terminal Region of E2 Glycoprotein of Classical Swine Fever Virus are Responsible for Viral Attenuation in Swine. Positive Strand RNA Virus International Conference Proceedings. P2-K27, p.116 Interpretive Summary:
Technical Abstract: We have previously reported that combining specific genetic information from the Classical Swine Fever Virus (CSFV) vaccine strain CS with that of virulent CSFV strain Brescia (BICv) resulted in disease attenuation for pigs. To identify the specific amino acids mediate attenuation, a series of chimeric viruses containing CS E2 residues in the context of the BICv were constructed. Chimera 357v, containing CS E2 residues 691 to 881 of CSFV polyprotein was virulent, while chimera 358v, containing CS E2 residues 882 to 1064 was attenuated in swine. Single or double substitutions of those amino acids in BICv E2 to CS E2 residues did not affect virulence. Furthermore, mutant 32v, with six substitutions between residues 975-1059, and mutant 33v, with six substitutions between residues 955-994, induced disease indistinguishable from BICv, while mutant 31v, with seven substitutions between residues 882-958, induced a delayed onset of disease. Progressive introduction of mutations into 31v resulted in two mutants 42v and 43v with 12 and 13 substitutions, respectively that were attenuated in swine. Mutant 43v, with an amino acid composition identical to 358v, was attenuated in swine indicating that all substitutions were necessary for attenuation of virulent BICv. Importantly, 358v protected swine from challenge with virulent BICv at 3 and 28 days post-infection. These virulence determinants can be utilized in the rational design of novel CSFV vaccines.