Low levels of foot-and-mouth disease virus 3C protease expression are required to achieve optimal capsid protein expression and processing in mammalian cells

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The foot-and-mouth disease virus (FMDV) capsid protein precursor (P1-2A) is processed by the virus-encoded 3C protease (3C(pro)) to produce VP0, VP3, VP1 and 2A. Within the virus-encoded polyprotein, the P1-2A and 3C(pro) can be expected to be produced at equivalent concentrations. However, using transient-expression assays, within mammalian cells, it is possible to modify the relative amounts of the substrate and protease. It has now been shown that optimal production of the processed capsid proteins from P1-2A is achieved with reduced levels of 3C(pro) expression, relative to the P1-2A, compared with that achieved with a single P1-2A-3C polyprotein. Expression of the FMDV 3C(pro) is poorly tolerated by mammalian cells and higher levels of the 3C(pro) greatly inhibit protein expression. In addition, it is demonstrated that both the intact P1-2A precursor and the processed capsid proteins can be efficiently detected by FMDV antigen detection assays. Furthermore, the P1-2A and the processed forms each bind to the integrin αvβ6, the major FMDV receptor. These results contribute to the development of systems which efficiently express the components of empty capsid particles and may represent the basis for safer production of diagnostic reagents and improved vaccines against foot-and-mouth disease.

Original languageEnglish
JournalThe Journal of general virology
Issue numberPt 6
Pages (from-to)1249-1258
Number of pages10
Publication statusPublished - Jun 2013

    Research areas

  • Animals, Capsid/metabolism, Capsid Proteins/genetics, Cell Line, Cricetinae, Cysteine Endopeptidases/genetics, Foot-and-Mouth Disease/virology, Foot-and-Mouth Disease Virus/enzymology, Gene Expression Regulation, Viral, Protein Processing, Post-Translational, Viral Proteins/genetics

ID: 257916597