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Title: Mutations in the Carboxyl Terminal Region of E2 Glycoprotein of Classical Swine Fever Virus is Responsible for Viral Attenuation in Swine

Author
item RISATTI, GUILLERMO - UNIV. CONNECTICUT, STORRS
item Holinka-Patterson, Lauren
item FERNANDEZ-SAINZ, IGNACIO - ORISE USDA, ARS, PIADC
item CARRILLO, CONSUELO - USDA, APHIS, FADDL, PIADC
item KUTISH, GERALD - UNIV. CONNECTICUT, STORRS
item LU, ZHIQIANG - DHS, ST, PIADC
item Zhu, James
item ROCK, DANIEL - FORMER USDA, ARS, PIADC
item Borca, Manuel

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/5/2007
Publication Date: 8/1/2007
Citation: Risatti, G., Holinka, L.G., Fernandez-Sainz, I., Carrillo, C., Kutish, G.F., 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 is Responsible for Viral Attenuation in Swine. Virology. 364 (2): 371-82.

Interpretive Summary: We have previously showed that a virulent strain of CSFV containing the E2 glycoprotein gene from vaccine strain was markedly attenuated in pigs. The identification of the amino acid residues responsible for the attenuation will be useful in the rational development of live attenuated vaccines (LAV). To identify them a series of chimeric viruses (fourteen different recombinant viruses) Results demonstrated that attenuation was the product of a complex interaction between at least 12 amino acid residues. Using that information, a candidate LAV strain was developed and tested against the challenge with the virulent virus either at 3 and 28 days post vaccination. Interestingly, pigs challenge at both times post vaccination resulted completely protected showing no CSF related clinical signs nor shedding of the challenge virus. In summary, a novel CSFV genetic virulence determinant associated with the E2 glycoprotein has been identified. These results will improve the understanding of the genetic basis of CSFV virulence and will permit future rational design of live attenuated CSF vaccines of enhanced safety, efficacy and utility.

Technical Abstract: We have previously showed that a virulent strain of CSFV containing the E2 glycoprotein gene from vaccine strain was markedly attenuated in pigs. The identification of the amino acid residues responsible for the attenuation will be useful in the rational development of live attenuated vaccines (LAV). To identify them, a series of chimeric viruses (fourteen different recombinant viruses) were designed and tested in their level of attenuation in pigs. Results demonstrated that attenuation was the product of a complex interaction between at least 12 amino acid residues. Using that information, a candidate LAV strain was developed and tested against the challenge with the virulent virus either at 3 and 28 days post vaccination. Interestingly, pigs challenged at both times post vaccination were completely protected showing no CSF related clinical signs nor virus shedding. In summary, a novel CSFV genetic virulence determinant associated with the E2 glycoprotein has been identified. These results will improve the understanding of the genetic basis of CSFV virulence and will permit future rational design of live attenuated CSF vaccines of enhanced safety, efficacy and utility.