Cleavages at the three junctions within the foot-and-mouth disease virus capsid precursor (P1–2A) by the 3C protease are mutually independent

Thea Kristensen, Joseph Newman, Su Hua Guan, Tobias J. Tuthill, Graham J. Belsham*

*Corresponding author for this work

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    Abstract

    The foot-and-mouth disease virus capsid precursor, P1–2A, is cleaved by the 3C protease (3Cpro) to VP0, VP3, VP1 and 2A. The P1–2A precursor (wt or mutant) was expressed alone or with 3Cpro and processing of P1–2A was determined. The VP2 K217R and VP3 I2P substitutions (near the VP0/VP3 junction) strongly reduced the processing at this junction by 3Cpro while the substitution VP2 K217E blocked cleavage. At the VP3/VP1 junction, the substitutions VP3 Q2221P and VP1 T1P each severely inhibited processing at this site. Blocking cleavage at either junction did not prevent processing elsewhere in P1–2A. These modifications were also introduced into full-length FMDV RNA; only wt and the VP2 K217R mutant were viable. Uncleaved VP0-VP3 and the processed products were observed within cells infected with the mutant virus. The VP0-VP3 was not incorporated into empty capsids or virus particles. The three junctions within P1–2A are processed by 3Cpro independently.
    Original languageEnglish
    JournalVirology
    Volume522
    Pages (from-to)260-270
    ISSN0042-6822
    DOIs
    Publication statusPublished - 2018

    Keywords

    • Picornavirus
    • Polyprotein
    • Virus assembly
    • Protease cleavage site
    • Structural proteins

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