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

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Bell-Sakyi L, Kohl A, Bente D A, Fazakerley J K (2012)

Tick cell lines for study of Crimean-Congo hemorrhagic fever virus and other arboviruses

Vector-Borne and Zoonotic Diseases 12 (9), 769-81
Publisher’s version: http://dx.doi.org/10.1089/vbz.2011.0766

Abstract

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
Publisher’s version: http://dx.doi.org/10.1016/j.inmuno.2012.03.002

Abstract

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.
Berryman S, Brooks E, Burman A, Hawes P, Roberts R, Netherton C, Monaghan P, Whelband M, Cottam E, Elazar Z, Jackson T, Wileman T (2012)

Foot-and-mouth disease virus induces autophagosomes during cell entry via a class III phosphatidylinositol 3-kinase-independent pathway

Journal of Virology 86 (23), 12940-12953
Publisher’s version: http://dx.doi.org/10.1128/jvi.00846-12

Abstract

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.
Bhatta D, Villalba M M, Johnson C L, Emmerson G D, Ferris N P, King D P, Lowe C R (2012)

Rapid detection of foot-and-mouth disease virus with optical microchip sensors

Procedia Chemistry 6, 2-10
Publisher’s version: http://dx.doi.org/10.1016/j.proche.2012.10.124

Abstract

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.
Biggs P M, Nair V (2012)

The long view: 40 years of Marek's disease research and Avian Pathology

Avian Pathology 41 (1), 3-9
Publisher’s version: http://dx.doi.org/10.1080/03079457.2011.646238

Abstract

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.
Bin Tarif A, Lasecka L, Holzer B, Baron M D (2012)

Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep

Veterinary Research 43, e71
Publisher’s version: http://dx.doi.org/10.1186/1297-9716-43-71

Abstract

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
Publisher’s version: https://naldc.nal.usda.gov/naldc/download.xhtml?id=54312&content=PDF

Abstract

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
Publisher’s version: http://dx.doi.org/10.1016/j.molbiopara.2012.03.004

Abstract

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.
Boros A, Pankovics P, Knowles N J, Reuter G (2012)

Natural interspecies recombinant bovine/porcine enterovirus in sheep

Journal of General Virology 93, 1941-1951
Publisher’s version: http://dx.doi.org/10.1099/vir.0.041335-0

Abstract

Members of the genus Enterovirus (family Picornaviridae) are believed to be common and widespread among humans and different animal species, although only a few enteroviruses have been identified from animal sources. Intraspecies recombination among human enteroviruses is a well-known phenomenon, but only a few interspecies examples have been reported and, to our current knowledge, none of these have involved non-primate enteroviruses. In this study, we report the detection and complete genome characterization (using RT-PCR and long-range PCR) of a natural interspecies recombinant bovine/porcine enterovirus (ovine enterovirus type 1; OEV-1) in seven (44 %) of 16 faecal samples from 3-week-old domestic sheep (Ovis aries) collected in two consecutive years. Phylogenetic analysis of the complete coding region revealed that OEV-1 (ovine/TB4-OEV/2009/HUN; GenBank accession no. JQ277724) was a novel member of the species Porcine enterovirus B (PEV-B), implying the endemic presence of PEV-B viruses among sheep. However, the 5' UTR of OEV-1 showed a high degree of sequence and structural identity to bovine enteroviruses. The presumed recombination breakpoint was mapped to the end of the 5' UTR at nucleotide position 814 using sequence and SimPlot analyses. The interspecies-recombinant nature of OEV-1 suggests a closer relationship among bovine and porcine enteroviruses, enabling the exchange of at least some modular genetic elements that may evolve independently.
Boyce M, Celma C C P, Roy P (2012)

Bluetongue virus non-structural protein 1 is a positive regulator of viral protein synthesis

Virology Journal 9, e178
Publisher’s version: http://dx.doi.org/10.1186/1743-422x-9-178

Abstract

Background: Bluetongue virus (BTV) is a double-stranded RNA (dsRNA) virus of the Reoviridae family, which encodes its genes in ten linear dsRNA segments. BTV mRNAs are synthesised by the viral RNA-dependent RNA polymerase (RdRp) as exact plus sense copies of the genome segments. Infection of mammalian cells with BTV rapidly replaces cellular protein synthesis with viral protein synthesis, but the regulation of viral gene expression in the Orbivirus genus has not been investigated. Results: Using an mRNA reporter system based on genome segment 10 of BTV fused with GFP we identify the protein characteristic of this genus, non-structural protein 1 (NS1) as sufficient to upregulate translation. The wider applicability of this phenomenon among the viral genes is demonstrated using the untranslated regions (UTRs) of BTV genome segments flanking the quantifiable Renilla luciferase ORF in chimeric mRNAs. The UTRs of viral mRNAs are shown to be determinants of the amount of protein synthesised, with the pre-expression of NS1 increasing the quantity in each case. The increased expression induced by pre-expression of NS1 is confirmed in virus infected cells by generating a replicating virus which expresses the reporter fused with genome segment 10, using reverse genetics. Moreover, NS1-mediated upregulation of expression is restricted to mRNAs which lack the cellular 3' poly (A) sequence identifying the 3' end as a necessary determinant in specifically increasing the translation of viral mRNA in the presence of cellular mRNA. Conclusions: NS1 is identified as a positive regulator of viral protein synthesis. We propose a model of translational regulation where NS1 upregulates the synthesis of viral proteins, including itself, and creates a positive feedback loop of NS1 expression, which rapidly increases the expression of all the viral proteins. The efficient translation of viral reporter mRNAs among cellular mRNAs can account for the observed replacement of cellular protein synthesis with viral protein synthesis during infection.

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