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

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Webb C R, Floyd T, Brien S, Oura C A L, Wood J L N (2011)

Bluetongue serotype 8 vaccine coverage in northern and south-eastern England in 2008

Veterinary Record 168 (16), 428
Publisher’s version: http://dx.doi.org/10.1136/vr.c6927

Abstract

A postal survey of all registered cattle and sheep farmers in East Anglia was carried out from July 2008 to determine bluetongue virus serotype 8 (BTV-8) vaccine uptake in the region. The vaccine was available to farmers in this region from May 2008. The survey was repeated in Cumbria and Northumberland at the beginning of 2009. In these regions, the vaccine was not available until September 1, 2008. Holding-level vaccine uptake was estimated to be 85 per cent (95 per cent confidence interval [CI] 83 to 87 per cent, n=1623) in East Anglia and 36 per cent (95 per cent CI 32 to 40 per cent, n=633) in northern England. A telephone follow-up of non-responders reduced these estimates to 79 and 29 per cent in East Anglia and northern England, respectively. In both regions, vaccine coverage was higher in sheep than in cattle, with 92 per cent of sheep in East Anglia having been vaccinated. The proportion of holdings that had applied the vaccine or were intending to apply the vaccine in 2009 in the northern region was 51 per cent (95 per cent CI 47 to 54 per cent, n=664), with a further 37 per cent undecided at the time of response.
Widdison S, Coffey T J (2011)

Cattle and chemokines: evidence for species-specific evolution of the bovine chemokine system. (Review)

Animal Genetics 42 (4), 341-352
Publisher’s version: http://dx.doi.org/10.1111/j.1365-2052.2011.02200.x

Abstract

The chemokine system comprises a family of small chemoattractant molecules that have roles in both the healthy and diseased organism. Chemokines act by binding specific receptors on the target cell surface and inducing chemotaxis. The human chemokine system is well characterized, with approximately fifty chemokines identified that fall into four families. The chemokines and their receptors are promiscuous in that one chemokine can often bind several receptors, and vice versa. Study of the bovine chemokine system has been restricted to date to a handful of chemokines, and the identification of bovine chemokines is largely based on the closest human homologue. This method of identification is prone to error and may result in the misassumption of function of a particular chemokine. Here, we review current knowledge of bovine chemokines and reassess the bovine chemokine system based on phylogenetic and syntenic approaches. The bovine chemokine system, for the most part, shows high similarity to the chemokine system of other mammals such as humans; however, differences have been identified. Cattle possess fewer chemokines than humans, yet also possess chemokines that have no obvious homologue in the human system. These ‘missing’ and ‘novel’ chemokines may represent functional differences between the bovine and human chemokine systems that may affect the way in which these species are able to respond to specific pathogen repertoires.
Widdison S, Watson M, Coffey T J (2011)

Early response of bovine alveolar macrophages to infection with live and heat-killed Mycobacterium bovis

Developmental and Comparative Immunology 35 (5), 580-591
Publisher’s version: http://dx.doi.org/10.1016/j.dci.2011.01.001

Abstract

Bovine tuberculosis (TB) is a disease of economic importance and a significant animal health and welfare issue. The alveolar macrophage (AlvM?) plays a vital role in the immune response to TB and recent studies provide insights into the interactions between M? and Mycobacterium bovis. Here we reveal the early transcriptional response of bovine AlvM? to M. bovis infection. We demonstrate up-regulation of immune response genes, including chemokines, members of the NF-?B pathway which may be involved in their transcription and also pro- and anti-apoptotic genes. M. bovis may therefore induce multiple mechanisms to manipulate the host immune response. We compared the response of AlvM? to infection with live and heat-killed M. bovis to determine transcriptional differences dependent on the viable pathogen. Several chemokines up-regulated following live M. bovis infection were not up-regulated after heat-killed M. bovis stimulation; hence the M? seems to differentiate between the two stimuli.
Windsor M A, Carr B V, Bankowski B, Gibson D, Reid E, Hamblin P, Gubbins S, Juleff N, Charleston B (2011)

Cattle remain immunocompetent during the acute phase of foot-and-mouth disease virus infection

Veterinary Research 42, 108
Publisher’s version: http://dx.doi.org/10.1186/1297-9716-42-108

Abstract

Infection of cattle with foot-and-mouth disease virus (FMDV) results in the development of long-term protective antibody responses. In contrast, inactivated antigen vaccines fail to induce long-term protective immunity. Differences between susceptible species have also been observed during infection with FMDV, with cattle often developing persistent infections whilst pigs develop more severe symptoms and excrete higher levels of virus. This study examined the early immune response to FMDV in naïve cattle after in-contact challenge. Cattle exposed to FMDV were found to be viraemic and produced neutralising antibody, consistent with previous reports. In contrast to previous studies in pigs these cattle did not develop leucopenia, and the proliferative responses of peripheral blood mononuclear cells to either mitogen or third party antigen were not suppressed. Low levels of type 1 interferon and IL-10 were detected in the circulation. Taken together, these results suggest that there was no generalised immunosuppression during the acute phase of FMDV infection in cattle.

Wu Z, Hu T, Kaiser P (2011)

Chicken CCR6 and CCR7 are markers for immature and mature dendritic cells respectively

Developmental and Comparative Immunology 35 (5), 563-567
Publisher’s version: http://dx.doi.org/10.1016/j.dci.2010.12.015

Abstract

In mammals, the CC chemokine receptors 6 and 7 (CCR6 and CCR7) play important roles in controlling the trafficking of dendritic cells (DC). CCR6 is expressed primarily on immature DC in the periphery and plays a role in the recruitment of immature DC to sites of potential antigen entry. On encountering pathogens. DC mature and migrate to secondary lymphoid organs where they present pathogen antigen to T cells to initiate specific adaptive immune responses. Maturation involves down-regulation of CCR6 but up-regulation of CCR7. To investigate the role of these two chemokine receptors in the function of DC in the chicken, a full-length chicken CCR7 (chCCR7) cDNA was cloned. Chicken CCR6 (chCCR6) was already available (Munoz et al., 2009). ChCCR7 shows the typical secondary structure of a seven-transmembrane G protein-coupled receptor and has 66% and 64% amino acid identity with human and mouse CCR7, respectively. Like its mammalian orthologues, chCCR7 mRNA was highly expressed in most lymphoid tissues (with the exception of the Harderian gland) and also in some non-lymphoid tissues (especially the heart, lung, skin and small intestine). Both chCCR6 and chCCR7 were expressed at the mRNA level in immature chicken bone marrow-derived dendritic cells (chBM-DC), as measured by real-time quantitative RT-PCR. After DC maturation following stimulation with LPS or CD40L, expression levels of chCCR6 mRNA were down-regulated, whereas those of chCCR7 were up-regulated, suggesting that these two chemokine receptors play a similar role in the trafficking of chicken DC as they do in mammals and that they act as markers of immature (chCCR6) and mature (chCCR7) DC.
Yoon S H, Park W, King D P, Kim H (2011)

Phylogenomics and molecular evolution of foot-and-mouth disease virus

Molecules and Cells 31 (5), 413-421
Publisher’s version: http://dx.doi.org/10.1007/s10059-011-0249-6

Abstract

This report describes the use of Bayesian methods to analyze polyprotein coding region sequences (n = 217) obtained from GenBank to define the genome-wide phylogeny of foot and mouth disease virus (FMDV). The results strongly supported the monophyly of five FMDV serotypes, O, A, Asia 1, C, and SAT 3, while sequences for the two remaining FMDV serotypes, SAT 1 and SAT 2 did not separate into entirely distinct clades. The phylogenomic tree revealed three sister-group relationships, serotype O + Asia 1, A + C, and SAT 1 + 3 + 2, with a new branching pattern: {[(O, Asia 1), (A, C)], (SAT 1, 2, 3)}. Within each serotype, there was no apparent periodic, geographic, or host species influence on the evolution of global FMDVs. Analysis of the polyprotein coding region of these sequences provided evidence for the influence of purifying selection on the evolution of FMDV. Using a Bayesian coalescent approach, the evolutionary rate of FMDV isolates that circulated during the years 1932-2007 was estimated to be 1.46 x 10(-3) substitutions/site/year, and the most recent common ancestor of the virus existed approximately 481 years ago. Bayesian skyline plot revealed a population expansion in the early 20(th) century that was followed by a rapid decline in population size from the late 20(th) century to the present day. These findings provide new insights into the mechanisms that impact on the evolution of this important livestock pathogen.
Zhao Y, Xu H, Yao Y, Smith L P, Kgosana L, Green J, Petherbridge L, Baigent S J, Nair V (2011)

Critical role of the virus-encoded microRNA-155 ortholog in the induction of Marek's disease lymphomas

PLoS Pathogens 7 (2), e1001305
Publisher’s version: http://dx.doi.org/10.1371/journal.ppat.1001305

Abstract

Notwithstanding the well-characterised roles of a number of oncogenes in neoplastic transformation, microRNAs (miRNAs) are increasingly implicated in several human cancers. Discovery of miRNAs in several oncogenic herpesviruses such as KSHV has further highlighted the potential of virus-encoded miRNAs to contribute to their oncogenic capabilities. Nevertheless, despite the identification of several possible cancer-related genes as their targets, the direct in vivo role of virus-encoded miRNAs in neoplastic diseases such as those induced by KSHV is difficult to demonstrate in the absence of suitable models. However, excellent natural disease models of rapid-onset Marek's disease (MD) lymphomas in chickens allow examination of the oncogenic potential of virus-encoded miRNAs. Using viruses modified by reverse genetics of the infectious BAC clone of the oncogenic RB-1B strain of MDV, we show that the deletion of the six-miRNA cluster 1 from the viral genome abolished the oncogenicity of the virus. This loss of oncogenicity appeared to be primarily due to the single miRNA within the cluster, miR-M4, the ortholog of cellular miR-155, since its deletion or a 2-nucleotide mutation within its seed region was sufficient to inhibit the induction of lymphomas. The definitive role of this miR-155 ortholog in oncogenicity was further confirmed by the rescue of oncogenic phenotype by revertant viruses that expressed either the miR-M4 or the cellular homolog gga-miR-155. This is the first demonstration of the direct in vivo role of a virus-encoded miRNA in inducing tumors in a natural infection model. Furthermore, the use of viruses deleted in miRNAs as effective vaccines against virulent MDV challenge, enables the prospects of generating genetically defined attenuated vaccines.

Wright C F, Morelli M J, Thebaud G, Knowles N J, Herzyk P, Paton D J, Haydon D T, King D P (2011)

Beyond the consensus: dissecting within-host viral population diversity of foot-and-mouth disease virus by using next-generation genome sequencing

Journal of Virology 85 (5), 2266-2275
Publisher’s version: https://doi.org/10.1128/JVI.01396-10

Abstract

The diverse sequences of viral populations within individual hosts are the starting material for selection and subsequent evolution of RNA viruses such as foot-and-mouth disease virus (FMDV). Using next-generation sequencing (NGS) performed on a Genome Analyzer platform (Illumina), this study compared the viral populations within two bovine epithelial samples (foot lesions) from a single animal with the inoculum used to initiate experimental infection. Genomic sequences were determined in duplicate sequencing runs, and the consensus sequence of the inoculum determined by NGS was identical to that previously determined using the Sanger method. However, NGS revealed the fine polymorphic substructure of the viral population, from nucleotide variants present at just below 50% frequency to those present at fractions of 1%. Some of the higher-frequency polymorphisms identified encoded changes within codons associated with heparan sulfate binding and were present in both foot lesions, revealing intermediate stages in the evolution of a tissue culture-adapted virus replicating within a mammalian host. We identified 2,622, 1,434, and 1,703 polymorphisms in the inoculum and in the two foot lesions, respectively: most of the substitutions occurred in only a small fraction of the population and represented the progeny from recent cellular replication prior to onset of any selective pressures. We estimated the upper limit for the genome-wide mutation rate of the virus within a cell to be 7.8 × 10?4 per nucleotide. The greater depth of detection achieved by NGS demonstrates that this method is a powerful and valuable tool for the dissection of FMDV populations within hosts.

King K, Chapman D, Argilaguet J M, Fishbourne E, Hutet E, Cariolet R, Hutchings G, Oura C A L, Netherton C L, Moffat K, Taylor G, Le Potier M F, Dixon L K, Takamatsu H H (2011)

Protection of European domestic pigs from virulent African isolates of African swine fever virus by experimental immunisation

Vaccine 29 (28), 4593-4600
Publisher’s version: http://dx.doi.org/10.1016/j.vaccine.2011.04.052

Abstract

African swine fever (ASF) is an acute haemorrhagic disease of domestic pigs for which there is currently no vaccine. We showed that experimental immunisation of pigs with the non-virulent OURT88/3 genotype I isolate from Portugal followed by the closely related virulent OURT88/1 genotype I isolate could confer protection against challenge with virulent isolates from Africa including the genotype I Benin 97/1 isolate and genotype X Uganda 1965 isolate. This immunisation strategy protected most pigs challenged with either Benin or Uganda from both disease and viraemia. Cross-protection was correlated with the ability of different ASFV isolates to stimulate immune lymphocytes from the OURT88/3 and OURT88/1 immunised pigs.

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