Sequence adaptations affecting cleavage of the VP1/2A junction by the 3C protease in foot-and-mouth disease virus-infected cells
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Sequence adaptations affecting cleavage of the VP1/2A junction by the 3C protease in foot-and-mouth disease virus-infected cells. / Gullberg, Maria; Polacek, Charlotta; Belsham, Graham J.
In: The Journal of general virology, Vol. 95, No. Pt 11, 11.2014, p. 2402-2410.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Sequence adaptations affecting cleavage of the VP1/2A junction by the 3C protease in foot-and-mouth disease virus-infected cells
AU - Gullberg, Maria
AU - Polacek, Charlotta
AU - Belsham, Graham J
N1 - © 2014 The Authors.
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Amino Acid Substitution
KW - Animals
KW - Binding Sites/genetics
KW - Capsid Proteins/chemistry
KW - Cells, Cultured
KW - Cricetinae
KW - Cysteine Endopeptidases/metabolism
KW - Foot-and-Mouth Disease Virus/classification
KW - Models, Molecular
KW - Mutagenesis, Site-Directed
KW - Protein Structure, Quaternary
KW - Serotyping
KW - Viral Proteins/metabolism
U2 - 10.1099/vir.0.068197-0
DO - 10.1099/vir.0.068197-0
M3 - Journal article
C2 - 25000961
VL - 95
SP - 2402
EP - 2410
JO - Journal of General Virology
JF - Journal of General Virology
SN - 0022-1317
IS - Pt 11
ER -
ID: 257915884