Partners: University of St Andrews

Current Staff: Prof. Martin Ryan, Dr. Garry Luke, Dr. Ekaterina Minskiya, Ms. Fiona Tulloch, Mr. John Nicholson and Mr. Ashley Pearson.

Previous Staff: Dr. Uday Pathania.

The Picornavirus Group has worked upon different aspects of picornavirus replication and over the years have published a number of papers with collaborators at the Pirbright Institute. We have utilised our knowledge of how FMDV generates it’s proteins to facilitate major breakthroughs in biomedicine (e.g. human gene therapies, production of induced human pluripotent stem cells) and biotechnology (e.g. transgenic animals, transgenic plants, high-value protein expression). More detailed information on the group’s research areas, research outputs etc. can be viewed on the picornavirus group web pages.

Selected FMDV-related Publications;

Forrest, S., Lear, Z., Herod, M.R., Ryan, M.D., Rowlands, D.J & Stonehouse, N.J. (2014). Inhibition of the FMDV sub-genomic replicon by RNA aptamers. J. Gen. Virol. (in the press)

Tulloch, F., Pathania, U., Luke, G.A., Nicholson, J., Stonehouse, N.J., Rowlands,, D.J., Jackson, T., Tuthill, T., Haas, J., Lamond, A.I. & Ryan, M.D. (2014). FMDV replicons encoding green fluorescent protein are replication competent. J. Virol. Methods (in the press)

Martínez-Salas, E. & Ryan, M.D. (2010). “Translation and Protein Processing” In Picornaviruses: Molecular Biology, Evolution and Pathogenesis. Ehrenfeld, E., Domingo, E. & Roos, R.P. eds. ASM Press, Washington DC, USA. 141- 161.

Brown, J.D. & Ryan, M.D. (2010). ‘Ribosome “Skipping”: “Stop-Carry On” or “StopGo” Translation’. In ‘Recoding: Expansion of Decoding Rules Enriches Gene Expression’. Atkins J.F. and Gesteland, R.F eds. Springer. pp 101-122.

Armer, H., Moffat, K., Wileman, T., Belsham, T., Jackson, T., Duprex, W.P., Ryan, M. & Monaghan, P. (2008). Foot-and-mouth disease virus, but not bovine enterovirus, targets the host cell cytoskeleton via the nonstructural protein 3Cpro. J. Virology 82, 10556- 10566.

Moffat, K., Knox, C., Howell, G., Clark, S.J., Yang, Y.G., Belsham, G.J., Ryan, M. & Wileman, T. (2007). Inhibition of the secretory pathway by the Foot and Mouth Disease Virus 2BC protein is reproduced by co-expression of 2B and 2C and the site of inhibition is determined by the subcellular location of 2C. J. Virol. 81, 1129-1139.

Moffat,K., Howell, G., Knox, C., Belsham, G.J., Monaghan, P., Ryan, M.D. & Wileman, T. (2005). Effects of Foot-and-Mouth Disease virus non-structural proteins on the structure and function of the early secretory pathway: 2BC but not 3A blocks ER to Golgi transport. J. Virol. 79, 4382-4395.

Knox, C., Moffat, K., Ali, S., Ryan, M. & Wileman, T. (2005). Foot-and-mouth disease virus replication sites form next to the nucleus and close to the Golgi apparatus, but exclude marker proteins associated with host membrane compartments. J. Gen. Virol. 86 687-696.

Ryan, M.D., Donnelly, M.L.L., Flint, M., Cowton, V.M., Luke, G., Hughes, L.E., Knox, C. & and de Felipe, P. (2004). “Foot-and-Mouth Disease Virus Proteinases”. In Foot-And-Mouth Disease pp 53-76.

Monaghan, P., Cook, H., Jackson, T., Ryan, M.D. & Wileman, T. (2004). The Ultrastructure of the developing replication site in foot-and-mouth disease virus-infected BHK-38 cells. J. Gen. Virol. 85, 933-946.

de Felipe, P. Hughes, L.E. Ryan, M.D. & Brown, J.D. (2003). Co-translational, intraribosomal cleavage of polypeptides by the foot-and-mouth disease virus 2A peptide. J. Biol. Chem. 278, 11441-11448.

Ryan, M.D., Luke, G., Hughes, L.E., Cowton, V.M., ten Dam, E., Li, X., Donnelly, M.L.L., Mehrotra, A. & Gani, D. (2002). “The Aphtho- and Cardiovirus ‘Primary’ 2A/2B Polyprotein ‘Cleavage’”. In Molecular Biology of the Picornaviruses. ASM Press. pp 213-223.

Donnelly, M.L.L., Luke, G., Mehrotra, A., Li, X., Hughes, L.E., Gani, D. & Ryan, M.D. (2001). Analysis of the aphthovirus 2A/2B polyprotein ‘cleavage’ mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal ‘skip’. J. Gen. Virol. 82, 1013-1025.

Donnelly, M.L.L., Hughes, L.E., Luke, G., Li, X., Mendoza, H., ten Dam, E., Gani, D. & Ryan, M.D. (2001). The ‘cleavage’ activities of FMDV 2A site-directed mutants and naturally-occurring ‘2A-Like’ sequences. J. Gen. Virol. 82, 1027-1041.

Collen, T., Baron, J., Childerstone, A., Corteyn, A., Doel, T.R., Flint, M., Garcia-Valcarcel, M., Parkhouse, R.M.E. & Ryan, M.D. (1998). Heterotypic recognition of recombinant FMDV proteins by bovine T-cells: The polymerase (P3Dpol) as an immunodominant immunogen. Virus Research 56, 125-133.

Mackay, D.K.J., Forsyth, M.A., Davies, P.R., Berlinzani, A., Belsham, G.J., Flint, M. & Ryan, M.D. (1998). Differentiating infection from vaccination in foot-and-mouth disease using a panel of recombinant, non-structural proteins in ELISA. Vaccine 16, 446-459.

Ryan, M.D. & Flint, M. (1997). Virus-encoded proteinases of the picornavirus super-group. J. Gen. Virol. 78, 699-723.

Donnelly, M., Gani, D., Flint, M., Monoghan, S. & Ryan, M.D. (1997). The cleavage activity of aphtho- and cardiovirus 2A proteins. J. Gen. Virol. 78, 13-21.

Garcia-Valcarel, M., Doel,T., Collen,T., Ryan, M.D. & Parkhouse, R.M.E. (1996). Recognition of Foot-and-Mouth Disease Virus (FMDV) and its capsid protein VP1 by bovine peripheral T-lymphocytes. J. Gen. Virol. 77, 727-735.

Ryan, M.D. & Drew, J. (1994). Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein. EMBO J. 134, 928-933.

Newman, J.F.E., Piatti, P.G., Gorman, B.M., Burrage, T.G., Ryan, M.D., Flint, M. & Brown, F. (1994). Foot-and-mouth disease virus particles contain replicase protein 3D. Proc. Natl. Acad. Sci. USA 91, 733-737.

Newman, J.F.E., Piatti, P.G., Ryan, M.D. & Brown, F. (1994). Function of minor polypeptides in foot-and-mouth disease virus and poliovirus. Trends in Microbiology 2, 494-497.

Ryan, M.D., King, A.M.Q. & Thomas, G.P. (1991). Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence. J. Gen. Virol. 72, 2727-2732.

Roosien, J., Belsham, G.J., Ryan, M.D., King, A.M.Q. & Vlak, J.M. (1990). Synthesis of foot-and-mouth disease virus capsid proteins in insect cells using baculovirus expression vectors. J. Gen. Virol. 71, 1703-1711.

Belsham, G.J., Brangwyn, J.K., Ryan, M.D., Abrams, C.C. & King, A.M.Q. (1990). Intracellular expression and processing of foot-and-mouth disease virus capsid precursors using vaccinia virus vectors; Influence of the L protease. Virology 176, 524-530.

Ryan, M.D., Belsham, G.J. & King, A.M.Q. (1989). Specificity of enzyme-substrate interactions in foot-and-mouth disease virus polyprotein processing. Virology 173, 35-45.

Belsham, G.J., Ryan, M.D. & Brangwyn, J.K. (1989). “Expression of self-processing foot-and-mouth disease virus capsid precursors by vaccinia virus recombinants” In Vaccines 89 pp 445-448.