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Virology. 2010 Jan 5;396(1):152-9. doi: 10.1016/j.virol.2009.10.020. Epub 2009 Nov 7.

The region between the two polyprotein initiation codons of foot-and-mouth disease virus is critical for virulence in cattle.

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Foreign Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, P.O. Box 848, Greenport, NY 11944-0848, USA.


To explore the role in viral pathogenesis of the region located between the two functional AUG (inter-AUG) in foot-and-mouth disease virus (FMDV), we derived viruses containing transposon (tn) inserts from a mutagenized cDNA infectious clone of FMDV (pA24-WT). Mutant viruses containing an in-frame 57-nt transposon insertion grew at a slower rate and had a smaller plaque size phenotype than the parental virus (A24-WT). A mutant virus containing a 51-nt deletion in inter-AUG had a similar phenotype in cell culture to that of A24-WT. When tested by aerosol inoculation in cattle (3 animals per virus), the deletion mutant was fully virulent as was A24-WT. Mutant viruses containing insertions in inter-AUG did not cause clinical disease or viremia. However, viruses that partially or totally removed the tn insertion during animal infection reverted to virulence in 2 inoculated steers. Therefore, this study identified inter-AUG as an FMDV viral virulence determinant in cattle infected by aerosol route.

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