The region between the two polyprotein initiation codons of foot-and-mouth disease virus is critical for virulence in cattle.
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.
Piccone
Maria E
ME
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.
Pacheco
Juan M
JM
Pauszek
Steven J
SJ
Kramer
Ed
E
Rieder
Elizabeth
E
Borca
Manuel V
MV
Rodriguez
Luis L
LL
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003062:Codon; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D009154:Mutation; D020815:Polyproteins / Q000096:biosynthesis / Q000235:genetics*; D014176:Protein Biosynthesis; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence; D014779:Virus Replication
D003062:Codon; D020815:Polyproteins; D014764:Viral Proteins