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United States Department of Agriculture

Agricultural Research Service

Title: Mutations in the classical swine fever virus NS4B protein affects virulence in swine

item Fernandez Sainz, Ignacio
item Gladue, Douglas
item Holinka, Lauren
item O'donnell, Vivian
item Gudmundsdottir, Ingegedur
item Prarat, Melanie
item Patch, Jared
item Golde, William
item Zhiqiang, Lu
item Risatti, Guillermo
item Zhu, James
item Borca, Manuel

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/30/2009
Publication Date: 12/6/2009
Citation: Fernandez Sainz, I., Gladue, D.P., Holinka-Patterson, L.G., O'Donnell, V.K., Gudmundsdottir, I., Prarat, M.V., Patch, J.R., Golde, W.T., Zhiqiang, L., Risatti, G.R., Zhu, J.J., Borca, M.V. 2009. Mutations in the classical swine fever virus NS4B protein affects virulence in swine. Proceedings. P. 143.

Interpretive Summary:

Technical Abstract: NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Interleukin-1 receptor (TIR)-like domain. This TIR-like motif harbors two conserved domains, box 1 and box 2, also observed in other members of the TIR superfamily, including Toll-like receptors (TLRs). Mutations within the BICv NS4B box 2 domain (V2566A, G2567A, I2568A) produced recombinant virus NS4B.VGIv, with a phenotype displaying affected transcriptional activation of TLR-7 -induced genes in swine macrophages, including a significant sustained increase of IL-6 mRNA accumulation. Transfection of swine macrophages with wild-type NS4B protein partially blocked the TLR-7 activating effect of Imiquimod R837. In vivo, NS4B.VGIv was completely attenuated in swine, displaying a reduced replication in the oronasal cavity and limited spread from the inoculation site to secondary target organs. Furthermore, the level and duration of IL-6 production in the tonsils of pigs intranasally inoculated with NS4B.VGIv was significantly higher than in animals infected with BICv. The peak of IL-6 production in infected animals paralleled the ability of animals infected with NS4B.VGIv to resist challenge with virulent BICv. Interestingly, treatment of peripheral blood monocuclear cell cultures with recombinant porcine IL-6 results in a significant decrease of BICv replication.

Last Modified: 10/17/2017
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