title: Sequence adaptations affecting cleavage of the VP1/2A junction by the 3C protease in foot-and-mouth disease virus-infected cells.
abstract: The foot-and-mouth disease virus (FMDV) capsid protein precursor P1-2A is cleaved by the virus-encoded 3C protease to VP0, VP3, VP1 and 2A. It was shown previously that modification of a single amino acid residue (K210E) within the VP1 protein and close to the VP1/2A cleavage site, inhibited cleavage of this junction and produced 'self-tagged' virus particles. A second site substitution (E83K) within VP1 was also observed within the rescued virus [Gullberg et al. (2013). J Virol 87: , 11591-11603]. It was shown here that introduction of this E83K change alone into a serotype O virus resulted in the rapid accumulation of a second site substitution within the 2A sequence (L2P), which also blocked VP1/2A cleavage. This suggests a linkage between the E83K change in VP1 and cleavage of the VP1/2A junction. Cells infected with viruses containing the VP1 K210E or the 2A L2P substitutions contained the uncleaved VP1-2A protein. The 2A L2P substitution resulted in the VP1/2A junction being highly resistant to cleavage by the 3C protease, hence it may be a preferred route for 'tagging' virus particles.
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Lindholm, Kalvehave DK-4771, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Gullberg
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Lindholm, Kalvehave DK-4771, Denmark.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Polacek
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Lindholm, Kalvehave DK-4771, Denmark.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Belsham
mesh_terms: D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D029544:Foot-and-Mouth Disease Virus / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D020836:Protein Structure, Quaternary; D012703:Serotyping; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; C442459:VP2 protein, Foot-and-mouth disease virus; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases