Key result
Introduction of the E83K substitution into a serotype O foot-and-mouth disease virus led to a secondary 2A L2P substitution, which highly resisted VP1/2A junction cleavage by the 3C protease.
The 2A L2P substitution in FMDV makes the VP1/2A junction highly resistant to cleavage by the 3C protease, offering a preferred route for 'tagging' virus particles.
E83K-induced L2P substitution confers 3C cleavage resistance in FMDV; leaves open consequences for viral fitness or attenuation strategies.
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.
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Gullberg et al. (2014) studied Foot-and-mouth disease virus (FMDV) infection. Viral sequence substitutions (E83K in VP1 and L2P in 2A) was evaluated on Cleavage of the VP1/2A junction by the 3C protease. Introduction of the E83K substitution into a serotype O foot-and-mouth disease virus led to a secondary 2A L2P substitution, which highly resisted VP1/2A junction cleavage by the 3C protease.
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