A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle

Authors: Pacheco Tobin, Juan; GLADUE, DOUGLAS - University Of Connecticut; Holinka-Patterson, Lauren; Arzt, Jonathan; Bishop, Elizabeth; Smoliga, George; Pauszek, Steven; BRACHT, ALEXA - Animal And Plant Health Inspection Service (APHIS); O'DONNELL, VIVIAN - University Of Connecticut; FERNANDEZ-SAINZ, IGNACIO - University Of Connecticut; FLETCHER, PAIGE - Oak Ridge Institute For Science And Education (ORISE); PICCONE, MARIA - Oak Ridge Institute For Science And Education (ORISE); Rodriguez, Luis; Borca, Manuel

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/5/2013
Publication Date: 11/1/2013
Publication URL: http://handle.nal.usda.gov/10113/59451
Citation: Pacheco Tobin, J., Gladue, D.P., Holinka-Patterson, L.G., Arzt, J., Bishop, E.A., Smoliga, G.R., Pauszek, S.J., Bracht, A.J., O'Donnell, V., Fernandez-Sainz, I., Fletcher, P., Piccone, M.E., Rodriguez, L.L., Borca, M.V. 2013. A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle. Virology. 446(1-2):260-267.

Interpretive Summary: Foot-and-mouth disease (FMD) continues to be one of the most economically devastating disease of livestock worldwide. There is limited information regarding the specific role of FMD virus proteins in determining host susceptibility. This work deals with the role of one of the FMDV non-structural proteins (3A) in determining disease in cattle and swine. Previous reports had suggested a possible relationship between a deletion in a particular region of the 3A protein and inability to produce disease in cattle, but these results were not conclusive. Here we report the construction of a mutant FMDV of the O1Campos subtype, having deleted an area of 20 amino acids in protein 3A. This virus was fully attenuated in cattle but not in swine. The results presented here unequivocally demonstrated that a 20 amino acid region of the 3A protein is responsible for determining the attenuation of the virus in cattle. This information will be applied to future development of better vaccines against this important disease.

Technical Abstract: The role of non-structural protein 3A in foot-and-mouth disease virus (FMDV) on the virulence in cattle has received significant attention. Particularly, a characteristic 10–20 amino acid deletion has been implicated as being responsible for virus attenuation in cattle: a 10 amino acid deletion in the naturally occurring, porcinophilic FMDVO1Taiwanese strain, and an approximate 20 amino acid deletion found in egg-adapted derivatives of FMDV serotypes O1 and C3. Previous reports using chimeric viruses linked the presence of these deletions to an attenuated phenotype in cattle, although results were not conclusive. We report here the construction of a FMDV O1Campos variant differing exclusively from the highly virulent parental virus in a 20 amino acid deletion between 3A residues 87–106, and its characterization in vitro and in vivo. We describe a direct link between a deletion in the FMDV 3A protein and disease attenuation in cattle.