The Pirbright Institute publication directory contains details of selected publications written by our researchers.

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Batten C A, Henstock M R, Bin-Tarif A, Steedman H M, Waddington S, Edwards L, Oura C A L (2012)

Bluetongue virus serotype 26: Infection kinetics and pathogenesis in Dorset Poll sheep

Veterinary Microbiology 157 (1-2), 119-124


Bluetongue virus serotype 26 (BTV-26) has recently been isolated from sheep in Kuwait. The aim of this study was to assess the pathogenicity and infection kinetics of BTV-26 in Dorset Poll sheep. Six sheep were experimentally infected with BTV-26 and samples taken throughout the study were used to determine the kinetics of infection using a pan specific BTV real time RT-PCR assay and two group specific ELISAs. Five of the six sheep showed mild clinical signs characteristic of bluetongue including conjunctivitis, reddening of the mouth mucosal membranes, slight oedema of the face and nasal discharge. Viral RNA was detected in 5 of the 6 sheep by real time RT-PCR, however the levels of viral RNA detected in the samples were lower and of shorter duration than seen with other field strains of BTV. Virus was isolated from the blood of infected animals at the peak of viraemia at around 9 dpi. Antibodies against BTV were first detected by 7 dpi using the early detection BTV ELISA and a little later (7-14 dpi) using a BTV specific competitive ELISA. Four of the five remaining sheep developed neutralising antibodies to BTV-26, measured by a serum neutralisation test (SNT), with titres (log(10)) ranging from 1.40 to 2.08.


Eubenangee virus has previously been identified as the cause of Tammar sudden death syndrome (TSDS). Eubenangee virus (EUBV), Tilligery virus (TILV), Pata virus (PATAV) and Ngoupe virus (NGOV) are currently all classified within the Eubenangee virus species of the genus Orbivirus, family Reoviridae. Full genome sequencing confirmed that EUBV and TILV (both of which are from Australia) show high levels of aa sequence identity (>92%) in the conserved polymerase VP1(Pol), sub-core VP3(T2) and outer core VP7(T13) proteins, and are therefore appropriately classified within the same virus species. However, they show much lower amino acid (aa) identity levels in their larger outer-capsid protein VP2 (


Continuous cell lines derived from many of the vectors of tick-borne arboviruses of medical and veterinary importance are now available. Their role as tools in arbovirus research to date is reviewed and their potential application in studies of tick cell responses to virus infection is explored, by comparison with recent progress in understanding mosquito immunity to arbovirus infection. A preliminary study of propagation of the human pathogen Crimean-Congo hemorrhagic fever virus (CCHFV) in tick cell lines is reported; CCHFV replicated in seven cell lines derived from the ticks Hyalomma anatolicum (a known vector), Amblyomma variegatum, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) microplus, and Ixodes ricinus, but not in three cell lines derived from Rhipicephalus appendiculatus and Ornithodoros moubata. This indicates that tick cell lines can be used to study growth of CCHFV in arthropod cells and that there may be species-specific restriction in permissive CCHFV infection at the cellular level.
Benitez-Ribas D, Borràs F E, del Val M, Lasarte J J, Marañón C, Martín-Gayo E, Sarobe P, Toribio M L, Montoya M (2012)

Dendritic cells: nearly 40 years later…

Inmunología 31 (2), 49-57


The immune system is probably one of the most complex cellular organizations in the body. Its complexity is not superfluous, but rather it is required to fulfill the complicated purpose of the immune system, namely: the recognition of the diverse repertoire of microorganisms and pathogens; the detection of neoplastic lesions originating from a range of tissues; and, while executing these tasks, the maintenance of peripheral tolerance by suppressing detrimental responses against healthy tissues. Since they were discovered by R. Steinman et al. nearly 40 years ago, dendritic cells (DCs) have emerged to be critical players in conducting the immune response to fulfill these roles. Here, we provide a general view on some aspects of DC immunology, highlighting the crucial role that R. Steinman's research in the DC field has played during all those years. This review will also give an outline on DC research in the particular aspects that represent the focus of research groups in Spain (recently organized as the DC.esp working group within SEI). Firstly, some of the subtypes of DC will be described, particularly thymic DC and their role on tolerance; then the DC role in tolerance will be examined, followed by their implications in viral infections. Finally, antigen targeting DCs will be reviewed taking into account the crucial contributions made by R. Steinman et al. This chapter will end by reviewing some DCs based therapies in viral infections.


Autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses to lysosomes for degradation or can be beneficial for viruses by providing specialized membranes for virus replication. Here, we show that the picornavirus foot-and-mouth disease virus (FMDV) induces the formation of autophagosomes. Induction was dependent on Atg5, involved processing of LC3 to LC3II, and led to a redistribution of LC3 from the cytosol to punctate vesicles indicative of authentic autophagosomes. Furthermore, FMDV yields were reduced in cells lacking Atg5, suggesting that autophagy may facilitate FMDV infection. However, induction of autophagosomes by FMDV appeared to differ from starvation, as the generation of LC3 punctae was not inhibited by wortmannin, implying that FMDV-induced autophagosome formation does not require the class III phosphatidylinositol 3-kinase (PI3-kinase) activity of vps34. Unlike other picornaviruses, for which there is strong evidence that autophagosome formation is linked to expression of viral nonstructural proteins, FMDV induced autophagosomes very early during infection. Furthermore, autophagosomes could be triggered by either UV-inactivated virus or empty FMDV capsids, suggesting that autophagosome formation was activated during cell entry. Unlike other picornaviruses, FMDV-induced autophagosomes did not colocalize with the viral 3A or 3D protein. In contrast, ?50% of the autophagosomes induced by FMDV colocalized with VP1. LC3 and VP1 also colocalized with the cellular adaptor protein p62, which normally targets ubiquitinated proteins to autophagosomes. These results suggest that FMDV induces autophagosomes during cell entry to facilitate infection, but not to provide membranes for replication.


Rapid identification of infectious disease pathogens such as foot-and-mouth disease virus (FMDV) during new outbreaks of disease is of fundamental importance in disease control. SpectroSens (TM) optical microchip sensors demonstrating rapid, label-free detection of FMDV are presented; these contain multiple high-precision planar Bragg gratings and function as low-cost, robust refractive-index sensors. Sensor selectivity to FMDV is imparted by functionalising the top-surface of specific sensing channels with anti-FMDV monoclonal antibodies (mAbs). Selective binding of cognate antigens within the test sample to surface-immobilised FMDV mAbs results in localised changes in refractive index within specific sensing channels; these antibody-antigen interactions manifest as increases in wavelength of light reflected from the multi-channel sensor chip (light is coupled into and out of the chip via optical fibres). Selective identification of FMDV within minutes of sample introduction has been demonstrated by referenced measurement of changes in sensor reflected wavelength from anti-FMDV channels against sensor controls; simplified 'snap-shot' assay data are displayed in the form of a simple yes/no readout using a robust, hand-portable device, with further semi-quantitative information available to the 'super-user'. The characteristics of the SpectroSens (TM) multiplexed detection platform highlight its potential for in-field detection of foot-and-mouth disease and prospective expansion into diagnoses of other infectious veterinary diseases.


Marek's disease (MD), named after the Hungarian veterinary pathologist over 100 years ago, is a major disease affecting poultry health worldwide. Research in the late 1960s that led to the identification of the causative herpesvirus and the development of a highly successful vaccine is undoubtedly one of the best success stories in veterinary medicine. As Avian Pathology is celebrating its 40th anniversary, we review the last four decades of MD research that has provided major advances in our understanding of the virus, the pathogenic mechanisms of the disease, methods of diagnosis and the control through different generations of vaccines. Particular attention has been paid to the contributions made by publications in Avian Pathology. Despite this tremendous progress, MD continues to pose major challenges particularly from increasing virulence and emergence of new pathotypes. Further research on the molecular mechanisms of the disease, genetic resistance, vaccine-induced protection and evolution of virulence will be needed to develop more sustainable control strategies in the coming years.


Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus.
Biswal J K, Sanyal A, Rodriguez L L, Subramaniam S, Arzt J, Sharma G K, Hammond J M, Parida S, Mohapatra J K, Mathapatii B S, Dash B B, Ranjan R, Rout M, Venketaramanan R, Misri J, Krishna L, Prasad G, Pathak K M L, Pattnaik B (2012)

Foot-and-mouth disease: global status and Indian perspective

Indian Journal of Animal Sciences 82, 109-131


Foot-and-mouth disease (FMD) is a highly contagious and transboundary viral disease of domesticated and wild cloven-hoofed animals. Wide prevalence of the disease in Asia and Africa associated with huge economic loss to the livestock farming and industry has increased the concern worldwide. The disease is a major threat to cattle, buffalo (both milk and meat) and pig production in endemic countries and therefore considered to cause food insecurity, both locally and globally. Currently, 6 serotypes of FMD virus (0, A, Asia-1, SAT-1,-2, and -3) are circulating globally, and serotype C has not been recorded since 1995. In India, the disease is caused by serotypes 0, A and Asia-1, of which serotype 0 is responsible for most of the outbreaks. Emergence and re-emergence of FMD virus genotypes/lineages has been detected in serotypes. Serotype A viruses have been continuously emerging in the nature necessitating frequent replacement of the vaccine strains. The knowledge generated in epidemiology, diagnosis and surveillance of the disease in the country has been instrumental in formulation and implementation of FMD Control Programme through regular 6 monthly vaccination with the aim to create disease free zones in India. The control programme, in operation since X Plan, has resulted in progressive and substantial reduction in occurrence of the disease and DIVA reactors/converters in vaccinated areas. The present review summarizes the disease, the causative agent, and epidemiology of FMD in India and the world.

Blake D P, Alias H, Billington K J, Clark E L, Mat-Isa M-N, Mohamad A-F-H, Mohd-Amin M-R, Tay Y-L, Smith A L, Tomley F M, Wan K-L (2012)

EmaxDB: Availability of a first draft genome sequence for the apicomplexan Eimeria maxima

Molecular and Biochemical Parasitology 184 (1), 48-51


Apicomplexan parasites are serious pathogens of animals and man that cause diseases including coccidiosis, malaria and toxoplasmosis. The importance of these parasites has prompted the establishment of genomic resources in support of developing effective control strategies. For the Eimeria species resources have developed most rapidly for the reference Eimeria tenella Houghton strain. The value of these resources can be enhanced by comparison with related parasites. The well characterised immunogenicity and genetic diversity associated with Eimeria maxima promote its use in genetics-led studies on coccidiosis and recommended its selection for sequencing. using a combination of sequencing technologies a first draft assembly and annotation has been produced for an E. maxima Houghton strain-derived clone (EmaxDB. The assembly of a draft genome sequence for E. maxima provides a resource for comparative studies with Eimeria and related parasites as demonstrated here through the identification of genes predicted to encode microneme proteins in E. maxima.


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