Foot-and-mouth disease virus

Foot-and-mouth disease virus (FMDV) is a picornavirus which causes an economically important disease of cloven-hoofed livestock. The main barrier to the establishment of the effective control of FMDV through vaccination is the establishment of persistent infections in infected and vaccinated ruminants. Such persistently infected animals provide a theoretical reservoir for infectious virus. The establishment of a persistent infection by FMDV suggests that the virus may inhibit components of the innate and/or adaptive immune defences.

A role for the non-structural proteins of picornaviruses in inhibition of host cell protein secretion has been identified. Thus, poliovirus 3A disrupts protein trafficking between the endoplasmic reticulum and Golgi apparatus, resulting in a reduction in interferon (IFN)-beta, IL-6 and IL-8 secretion and a reduction in cell surface expression of MHC class I and the TNF receptor. These effects could be significant in viral pathogenesis and limit both the inflammatory and immune responses associated with infection. In contrast to poliovirus, the FMDV 2BC, and not the 3A protein, blocks the secretory pathway. The observation that FMDV 2BC inhibits the delivery of membrane proteins to the cell surface raises the possibility that the 2BC protein may modulate recognition of infected cells by the immune system. Such effects could contribute to the development of persistent FMDV infections.

We are also engaged in the development of FMD DNA vaccines which do not express 2BC but incorporate the FMDV 3D protein to help T cell responses.

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Our current FMDV studies include:

  • Analysis of the role of FMDV 2BC in the pathogenesis of infection and in immune evasion
  • Identification of the region(s) of 2BC involved in inhibition of protein trafficking
  • Investigation of the relationship between differences in the innate immune response, e.g. NK and g/d T cells, to FMDV and the establishment of the carrier state in ruminants
  • Optimisation and evaluation of FMD DNA vaccine in cattle.

We are also collaborating with Paul Barnett and Satya Parida on vaccine aspects of foot-and-mouth disease virus

Publications:

  • Y. Li, C.M.A. Stirling, M.S. Denyer, P. Hamblin, H.-H. Takamatsu & P.V. Barnett (2008) Dramatic improvement in FMD DNA vaccine efficacy and cross-serotype antibody induction in pigs following a protein boost. Vaccine 26:2647-2656. [Abstract].
  • A. Brun, E. Albina, J. Bárcena, T. Barret, E. Blanco, B. Borrego, D.A.G Chapman, M. Czub, L.K. Dixon, D. Dory, J. Escribano, G.M. Keil, B. Klonjkowski, G. Le Gall-Reculé, M.-F. LePotier, J. Ortego, J. Richardson & H.-H. Takamatsu (2008) Antigen delivery systems for veterinary vaccine development. Viral vector-based delivery systems. Vaccine 26:6508-6528. [Abstract].
  • K. Moffat, C. Knox, G. Howell, S.J. Clark, H. Yang, G.J. Belsham, M.D. Ryan & T. Wileman (2007) Inhibition of the secretory pathway by the Foot-and-Mouth Disease Virus 2BC protein is reproduced by co-expression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C. Journal of Virology. 81 1129-39. [Abstract].
  • C. Netherton, K. Moffat, E. Brooks & T. Wileman (2007) A guide to viral inclusions, membrane rearrangements, factories, and viroplasm produced during virus replication. Advances in Virus Research 70:101-82 [Abstract].
  • V. Niborski, Y. Li, F. Brennam, M. Lane, A.M. Torché, M. Remond, M. Bonneau, S. Riffault, C. Stirling, G. Hutchings, H. Takamatsu, P. Barnett, B. Charley & I. Schwarz-Cornil (2006) Efficacy of particle-based DNA delivery for vaccination of sheep against FMDV. Vaccine, 24:7204-7213. [Abstract].
  • Y. Li, N. Aggarwal, H.-H. Takamatsu, C.M. Sterling, C. Voyce, & P.V. Barnett (2006) Enhancing immune responses against a plasmid DNA vaccine encoding a FMDV empty capsid from serotype O. Vaccine 24:4602-4606. [Abstract].
  • H.-H. Takamatsu, M.S. Denyer, C. Stirling, S. Cox, N. Aggarwal, P. Dash, T.E. Wileman & P.V. Barnett (2006) Porcine T cells: Possible roles on the innate and adaptive immune responses following virus infection. Veterinary Immunology and Immunopathology, 112:49-61. [Abstract].
  • K. Moffat, G. Howell, C. Knox, G.J. Belsham, P. Monaghan, M.D. Ryan & T. Wileman (2005) Effects of foot-and-mouth disease virus nonstructural proteins on the structure and function of the early secretory pathway: 2BC but not 3A blocks endoplasmic reticulum-to-Golgi transport. Journal of Virology. 79:4382-4395 [Abstract].