Staff: Prof. Terry Jackson, Dr. Toby Tuthill,
Dr. Don King, Dr. Lidia Lasecka, Dr. Sarah Gold
Institute (formerly the Institute for Animal Health) contains
internationally recognised expertise in virology, immunology, genetics,
pathogenesis, molecular epidemiology, diagnostics, mathematical biology
and bioimaging. Significant investment has been made to redevelop the
Pirbright site and the construction and upgrading of facilities is well
underway. The inter-disciplinary nature of the institute provides an
environment where basic and applied science is combined so fundamental
discoveries can be developed with in-house expertise in global disease
control and the commercialisation of science.
Institute specialises in the control of viral diseases and is the only
site in the UK licensed for work with foot-and-mouth disease virus (FMDV).
Dr Terry Jackson, Dr Toby Tuthill and Dr Don King have combined interests
which include molecular mechanisms of FMDV entry, replication and assembly;
viral population diversity and evolution; molecular epidemiology and
Tuthill’s research focuses on understanding fundamental
molecular mechanisms of picornavirus (FMDV and related viruses) membrane
penetration, replication, capsid assembly and genome packaging and the
application of this knowledge towards novel targets/strategies for disease
control. We use a variety of approaches such as: cell culture, molecular
biology, fluorescent microscopy, recombinant proteins, model membranes
and electron microscopy. Structural biology approaches such as X-ray
crystallography and nuclear magnetic resonance are carried out in collaboration
with universities such as Oxford and Harvard.
projects include research to answer the following questions: How does
FMDV interact with membranes? What is the role of picornavirus capsid
protein VP4 in membrane penetration? How does myristoylation and proteolytic
processing control the properties of FMDV pentamers? What confers specificity
to picornavirus packaging?
plate-based high-throughput assay for virus stability and vaccine formulation.
Walter TS, Ren J, Tuthill TJ, Rowlands DJ, Stuart DI, Fry EE. J Virol
Methods. 2012 Oct;185(1):166-70. Epub 2012 Jun 26.
structure of equine rhinitis A virus in complex with its sialic acid
receptor. Fry EE, Tuthill TJ, Harlos K, Walter TS, Rowlands DJ, Stuart
DI. J Gen Virol. 2010 Aug;91(Pt 8):1971-7. Epub 2010 Apr 28.
Tuthill TJ, Groppelli E, Hogle JM, Rowlands DJ. Curr Top Microbiol Immunol.
entry of the aphthovirus equine rhinitis A virus is dependent on endosome
acidification. Groppelli E, Tuthill TJ, Rowlands DJ. J Virol. 2010 Jun;84(12):6235-40.
Epub 2010 Apr 7.
rhinitis A virus and its low pH empty particle: clues towards an aphthovirus
entry mechanism? Tuthill TJ, Harlos K, Walter TS, Knowles NJ, Groppelli
E, Rowlands DJ, Stuart DI, Fry EE. PLoS Pathog. 2009 Oct;5(10):e1000620.
Epub 2009 Oct 9.
disease virus assembly: processing of recombinant capsid precursor by
exogenous protease induces self-assembly of pentamers in vitro in a
myristoylation-dependent manner. Goodwin S, Tuthill TJ, Arias A, Killington
RA, Rowlands DJ. J Virol. 2009 Nov;83(21):11275-82. Epub 2009 Aug 26.
VP4 of human rhinovirus induces permeability in model membranes. Davis
MP, Bottley G, Beales LP, Killington RA, Rowlands DJ, Tuthill TJ. J
Virol. 2008 Apr;82(8):4169-74. Epub 2008 Feb 6.
models of rhinovirus-induced disease and exacerbation of allergic airway
inflammation. Bartlett NW, Walton RP, Edwards MR, Aniscenko J, Caramori
G, Zhu J, Glanville N, Choy KJ, Jourdan P, Burnet J, Tuthill TJ, Pedrick
MS, Hurle MJ, Plumpton C, Sharp NA, Bussell JN, Swallow DM, Schwarze
J, Guy B, Almond JW, Jeffery PK, Lloyd CM, Papi A, Killington RA, Rowlands
DJ, Blair ED, Clarke NJ, Johnston SL. Nat Med. 2008 Feb;14(2):199-204.
Epub 2008 Feb 3.
of biofilms associated with dentures and toothbrushes by tetrasodium
EDTA. Devine DA, Percival RS, Wood DJ, Tuthill TJ, Kite P, Killington
RA, Marsh PD. J Appl Microbiol. 2007 Dec;103(6):2516-24.
of hepatitis C virus p7 membrane channels in a liposome-based assay
system. StGelais C, Tuthill TJ, Clarke DS, Rowlands DJ, Harris M, Griffin
S. Antiviral Res. 2007 Oct;76(1):48-58. Epub 2007 Jun 4.
of early steps in the poliovirus infection process: receptor-decorated
liposomes induce conversion of the virus to membrane-anchored entry-intermediate
particles. Tuthill TJ, Bubeck D, Rowlands DJ, Hogle JM. J Virol. 2006
among rhinovirus serotypes for a variant ICAM-1 receptor molecule. Xiao
C, Tuthill TJ, Bator Kelly CM, Challinor LJ, Chipman PR, Killington
RA, Rowlands DJ, Craig A, Rossmann MG. J Virol. 2004 Sep;78(18):10034-44.
respiratory epithelial cells support efficient replication of human
rhinovirus. Tuthill TJ, Papadopoulos NG, Jourdan P, Challinor LJ, Sharp
NA, Plumpton C, Shah K, Barnard S, Dash L, Burnet J, Killington RA,
Rowlands DJ, Clarke NJ, Blair ED, Johnston SL. J Gen Virol. 2003 Oct;84(Pt
Jackson‘s group carries out novel, fundamental
research aimed at improving knowledge of the mechanisms of infection
by foot-and-mouth disease virus (FMDV). The principle areas of our research
are the mechanisms of FMDV endocytosis and formation of the viral replication
complex. Through these studies we hope to gain a better understanding
of how FMDV replicates, and to inform applied research for control of
this important animal pathogen.
use integrated approaches combining biochemical, molecular- and cell-biology
techniques with reverse genetics and advanced microscopy (confocal-
and electron-microscopy) to ask fundamental questions about how virus
particles attach to cells, how they are internalized by endocytosis,
and how they use host-cell membranes for replication. We are using knowledge
of FMDV receptors to improve growth of vaccine strains of the virus
in cultured cells and to develop FMDV receptors as ‘universal’
virus-capture ligands for use in diagnostic assays. To achieve replication,
FMDV dramatically reorganizes internal cellular membranes to provide
specialized sites for formation of viral replication complexes. We also
study these events as we wish to determine what triggers membrane rearrangements
in infected cells, as well as identify the cellular origin of the replication
membranes and what properties make them favourable for replication.
S, Brooks E, Burman A, Hawes P, Roberts R, Netherton C, Monaghan P,
Whelband M, Cottam E, Elazar Z, Jackson T, Wileman T. FMDV induces autophagosomes
during cell entry via a class III PI3K-independent pathway. 2012 J Virol.
J, Jackson T, Doel C, Fry E, Stuart D, Harmsen MM, Charleston B, Juleff
N. Characterization of epitope-tagged foot-and-mouth disease virus.
2012 J Gen Virol. 93: 2371-2381.
L, Jackson T, Bøtner A, Belsham GJ. Capsid coding sequences of
foot-and-mouth disease viruses are determinants of pathogenicity in
pigs. 2012 Vet Res. May 24;43(1):46.
Burman, Gold, Shaw, Jackson and Ferris. Integrin sub-unit expression
in cell cultures used for the diagnosis of foot-and-mouth disease. 2011
Vet. Immunol. Immunopathol. 15; 140(3-4):259-65.
Kakker, Barbezange, Berryman, Jackson and Belsham. The capsid proteins
from field strains of foot-and-mouth disease virus confer a pathogenic
phenotype in cattle on an attenuated, cell culture adapted, virus. 2011
J. Gen. Virol. 92:1141-1151
Windsor, McLaughlin, Hope, Jackson and Charleston. Foot-and-mouth disease
virus exhibits an altered tropism in the presence of specific immunoglobulins,
enabling productive infection and killing of dendritic cells. 2011 J.
Barnett, Denyer, Jackson, Stirling, Hawes, Simpson, Monaghan and Takamatsu.
Foot-and-mouth disease virus only replicates transiently in well-differentiated
porcine nasal epithelial cells. 2010 J. Virol. 84:9149 – 9160.
Monaghan, Mertens and Jackson. A clathrin independent macropinocytosis-like
entry mechanism used by bluetongue virus-1 during infection of BHK cells.
2010 PLoS ONE: Research Article, published 29 Jun 2010 10.1371/journal.pone.0011360.
Berryman, Monaghan, Belsham and Jackson. A Dominant-Negative Mutant
of rab5 Inhibits Infection of Cells by Foot-and-Mouth Disease Virus:
Implications for Virus Entry. 2009 J. Virol. 83:6247-6256.
Moffat, Wileman, Belsham, Jackson, Duprex, Ryan and Monaghan. Foot-and-mouth
disease virus, but not bovine enterovirus, targets the host cell cytoskeleton,
via the non-structural protein 3Cpro 2008 J. Virol. 82:10556-10566.
Burman, Clark, Berryman, Howard, Hart, Marshall and Jackson. Foot-and-Mouth
Disease Virus Forms a Highly Stable, EDTA-Resistant Complex with Its
Principal Receptor, Integrin alpha-v/beta-6: Implications for Infectiousness.
2008 J. Virol. 82:1537-1546.
Clark, Abrescia, Fry, Stuart and Jackson. Specificity of the VP1 GH
Loop of Foot-and-Mouth Disease Virus for alpha-v Integrins. 2006 J.
Gold, Simpson, Zhang, Weinreb, Violette, Alexandersen and Jackson. The
alpha-v/beta-6 integrin receptor for foot-and-mouth disease virus is
expressed constitutively on the epithelial cells targeted in cattle.
2005 J. Gen. Virol. 86:2769-2780
Clark, Monaghan and Jackson. Early Events in Integrin alpha-v/beta-6
Mediated Cell Entry of Foot-and-Mouth Disease Virus. 2005 J. Virol.
Newman, Curry, Najjam, Jackson, Blakemore, Lea, Miller, Burman, King
and Stuart. Structure of Foot-and-mouth disease virus serotype A1061
alone and complexed with oligosaccharide receptor: receptor conservation
in the face of antigenic variation. 2005 J. Gen. Virol. 86:1909-1920.
Cook, Jackson, Ryan and Wileman. The ultrastructure of the developing
replication site in foot-and-mouth disease virus-infected BHK-38 cells.
2004 J. Gen. Virol. 85:933-946.
Clark, Berryman, Burman, Cambier, Mu, Nishimura and King. Integrin alpha-v/beta-8
Functions as a Receptor for Foot-and-Mouth Disease Virus: Role of the
beta-Chain Cytodomain in Integrin-Mediated Infection. 2004 J. Virol.
Mould, Sheppard and King. The integrin alpha-v/beta1 is a receptor for
foot-and-mouth disease virus. 2002 J. Virol. 76:935-941.
Sheppard, Denyer, Blakemore and King. The epithelial integrin alpha-v/beta-6
is a receptor for foot-and-mouth disease virus. 2000 J. Virol. 74:4949-4956.
Lea, Jackson, Newman, Ellard, Blakemore, Abu-Ghazaleh, Samule, King
and Stuart. The Structure and Function of a Foot-and-mouth-disease Virus
/oligosaccharide receptor complex. 1999 EMBO 18:543-554.
Ellard, Abu-Ghazaleh, Brookes, Blakemore, Corteyn, Stuart, Newman and
King. Efficient infection of cells in culture by Type-O foot-and-mouth
disease virus requires binding to cell surface heparan sulfate. 1996
J. Virol. 70:5282-5287.
King heads the Molecular Characterisation and Diagnostics group
at the Pirbright Institute. He has a background in veterinary virology
and immunology (University of Leeds, University of California, Davis),
and is interested in understanding the processes that drive the evolution
of positive-stranded viruses such as FMDV.
manages the core-sequencing facility at the Pirbright Institute that
routinely generates complete genome sequences for FMDV, and (in collaboration
with Professor Dan Haydon at the University of Glasgow) has pioneered
novel analytical pipelines to apply Next-Generation Sequencing methods
(Illuminia) to allow the within sample sequence diversity of FMDV to
holds a BBSRC grant to investigate viral evolution (BB/I014314/1: Beyond
the consensus: defining the significance of foot-and-mouth disease viral
sequence diversity) and is also a co-investigator on two further BBSRC
grants (BB/F009186: Identifying epitopes that induce antibody mediated
protection against foot-and-mouth disease using reverse genetics) and
(BB/H009302/1: Towards the strategic control of endemic foot-and-mouth
disease in Africa:). Work within the group (funded by Defra) develops
and applies new molecular technologies for the detection and characterisation
of important livestock disease agents such as FMD.
methods underpin the routine diagnostic work of the World Reference
Laboratory for FMD (Under the auspices of the FAO, OIE and EU), and
were central to the UK national control activities during the FMD outbreaks
in 2007. He also coordinates projects funded by EU-FP7, Food-and Agricultural
Organisation of the UN to investigate the maintenance of FMD in countries
where disease is endemic (Tanzania, Turkey, Malaysia and China).
N., Valdazo-González B., Wadsworth J., Wright C. F., Charleston
B., Paton D. J., King D. P. and Knowles N. J. Accumulation of nucleotide
substitutions occurring during experimental transmission of foot-and-mouth
disease virus. Journal of General Virology (IN PRESS).
B., Polihronova L., Alexandrov T., Normann P., Knowles N. J., Hammond
J. M., Georgiev G. K., Özyörük F., Sumption K. J. Belsham
G. J. and King D. P. Reconstruction of the transmission history of RNA
virus outbreaks using full genome sequences; foot-and-mouth disease
virus in Bulgaria in 2011. PLoS ONE (IN PRESS).
N. J., He J., Shang Y., Wadsworth J., Valdazo-González B., Onosato
H., Fukai K., Morioka K., Yoshida K., Cho I.-S., Kim S.-M., Park J.-H.,
Lee K.-N., Luk G., Borisov V., Scherbakov A., Timina A., Bold D., Nguyen
T., Paton D. J., Hammond J. M., Liu X. and King D. P. (2012) Emergence
of Southeast Asian Foot-and-mouth disease viruses in East Asia. Emerging
Infectious Diseases. 18 (3): 499-501.
N. F., Firat-Saraç M., Radford A. D., Knowles N. J. and King
D. P. (2011) Comparative sequence analysis of representative foot-and-mouth
disease virus genomes from Southeast Asia. Virus Genes 43: 41-45.
N. F., Hussein N. M., Wadsworth J., Radford A. D., Knowles N. J. and
King D. P. (2011) Phylogeography of foot-and-mouth disease virus types
O and A in Malaysia and surrounding countries. Infection, Genetics and
Evolution 11: 320-328.
C. F., Morelli M. J., Thébaud G., Knowles N. J. Herzyk P., Paton
D. J. Haydon D. T. and King D. P. (2011) Beyond the consensus: dissecting
within-host population diversity of foot-and-mouth disease virus using
next-generation sequencing. Journal of Virology 85 (5): 2266-2275.
in world-class bioscience research and training on behalf of the UK