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

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Radia D, Bond K, Limon G, van Winden S, Guitian J (2013)

Relationship between periparturient management, prevalence of JD and economic losses foregone in UK dairy herds

Veterinary Record 173 (14), 343
Publisher’s version: http://dx.doi.org/10.1136/vr.101408

Abstract

Johne's disease (JD) is an infectious, progressive, gastrointestinal disease affecting ruminants. Calves are mostly infected in their first six months of life, or in utero. We investigated the impact of specific periparturient management practices on within-herd JD prevalence and economic losses foregone in UK dairy herds by means of data synthesis (systematic appraisal of published evidence and expert elicitation) and use of a pre-existing simulation model. Our results show the scarcity of accurate estimates of the impact of specific periparturient management practices on within-herd JD prevalence, which could, in part, be explained by challenges associated with the chronic nature of JD. Management practices aiming to limit the faecal-oral transmission route of Mycobacterium avium subspecies paratuberculosis (MAP) were found to be most effective at reducing within-herd prevalence of JD. Practices aiming to limit MAP transmission via colostrum and milk were found to be less effective. Losses foregone for a hypothetical herd of 200 milking cows were considerable; based on the assumptions, it is reasonable to expect between £7000 and £11,000 of losses foregone when management practices are implemented as a package of measures. The findings of this study are envisaged to enable farmers and veterinarians to make more informed decisions on changes to periparturient management to control JD.

McFadden N, Arias A, Dry I, Bailey D, Witteveldt J, Evans D J, Goodfellow I, Simmonds P (2013)

Influence of genome-scale RNA structure disruption on the replication of murine norovirus--similar replication kinetics in cell culture but attenuation of viral fitness in vivo

Nucleic Acids Research 41 (12), 6316-6331
Publisher’s version: http://dx.doi.org/10.1093/nar/gkt334

Abstract

Mechanisms by which certain RNA viruses, such as hepatitis C virus, establish persistent infections and cause chronic disease are of fundamental importance in viral pathogenesis. Mammalian positive-stranded RNA viruses establishing persistence typically possess genome-scale ordered RNA secondary structure (GORS) in their genomes. Murine norovirus (MNV) persists in immunocompetent mice and provides an experimental model to functionally characterize GORS. Substitution mutants were constructed with coding sequences in NS3/4- and NS6/7-coding regions replaced with sequences with identical coding and (di-)nucleotide composition but disrupted RNA secondary structure (F1, F2, F1/F2 mutants). Mutants replicated with similar kinetics to wild-type (WT) MNV3 in RAW264.7 cells and primary macrophages, exhibited similar (highly restricted) induction and susceptibility to interferon-coupled cellular responses and equal replication fitness by serial passaging of co-cultures. In vivo, both WT and F1/F2 mutant viruses persistently infected mice, although F1, F2 and F1/F2 mutant viruses were rapidly eliminated 1-7 days post-inoculation in competition experiments with WT. F1/F2 mutants recovered from tissues at 9 months showed higher synonymous substitution rates than WT and nucleotide substitutions that potentially restored of RNA secondary structure. GORS plays no role in basic replication of MNV but potentially contributes to viral fitness and persistence in vivo.

Bergmann S, Beard P M, Pasche B, Lienenklaus S, Weiss S, Gahan C G M, Schughart K, Lengeling A (2013)

Influence of internalin a murinisation on host resistance to orally acquired listeriosis in mice

BMC Microbiology 13, 90
Publisher’s version: http://dx.doi.org/10.1186/1471-2180-13-90

Abstract

Background: The bacterial surface protein internalin (InlA) is a major virulence factor of the food-born pathogen Listeria monocytogenes. It plays a critical role in the bacteria crossing the host intestinal barrier by a species-specific interaction with the cell adhesion molecule E-cadherin. In mice, the interaction of InlA with murine E-cadherin is impaired due to sequence-specific binding incompatibilities. We have previously used the approach of 'murinisation' to establish an oral listeriosis infection model in mice by exchanging two amino acid residues in InlA. This dramatically increases binding to mouse E-cadherin. In the present study, we have used bioluminescent murinised and non-murinised Listeria strains to examine the spatiotemporal dissemination of Listeria in four diverse mouse genetic backgrounds after oral inoculation. Results: The murinised Listeria monocytogenes strain showed enhanced invasiveness and induced more severe infections in all four investigated mouse inbred strains compared to the non-murinised Listeria strain. We identified C57BL/6J mice as being most resistant to orally acquired listeriosis whereas C3HeB/FeJ, A/J and BALB/cJ mice were found to be most susceptible to infection. This was reflected in faster kinetics of Listeria dissemination, higher bacterial loads in internal organs, and elevated serum levels of IL-6, IFN-gamma, TNF-alpha and CCL2 in the susceptible strains as compared to the resistant C57BL/6J strain. Importantly, murinisation of InlA did not cause enhanced invasion of Listeria monocytogenes into the brain. Conclusion: Murinised Listeria are able to efficiently cross the intestinal barrier in mice from diverse genetic backgrounds. However, expression of murinized InlA does not enhance listerial brain invasion suggesting that crossing of the blood brain barrier and crossing of the intestinal epithelium are achieved by Listeria monocytogenes through different molecular mechanisms.

Formisano P, Aldridge B, Alony Y, Beekhuis L, Davies E, Del Pozo J, Dunn K, English K, Morrison L, Sargison N, Seguino A, Summers B A, Wilson D, Milne E, Beard P M (2013)

Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease

Veterinary Parasitology 193 (1-3), 252-255
Publisher’s version: http://dx.doi.org/10.1016/j.vetpar.2012.12.016

Abstract

Protozoal merozoites were identified in the cerebrospinal fluid of two sheep with neurological disease in the UK. Polymerase chain reaction (PCR) identified the merozoites as Sarcocystis capracanis, a common protozoal pathogen of goats. This is the first report of this species infecting sheep and may represent an aberrant infection with sheep acting as dead end hosts, or alternatively could indicate that sheep are able to act as intermediate hosts for S. capracanis, widening the previously reported host range of this pathogen. It is possible that S. capracanis is a previously unrecognised cause of ovine protozoal meningoencephalitis (OPM) in the UK.

Reid E (2013)

The characterisation of bovine plasmacytoid dendritic cells and their interaction with foot and mouth disease virus (FMDV) and bovine viral diarrhoea virus (BVDV) - (PhD Thesis: University of Surrey)

, 305 pp
Publisher’s version:
Yao Y, Charlesworth J, Nair V, Watson M (2013)

MicroRNA expression profiles in avian haemopoietic cells

Frontiers in Genetics 4, 153-153
Publisher’s version: http://dx.doi.org/10.3389/fgene.2013.00153

Abstract

MicroRNAs (miRNAs) are small, abundant, non-coding RNAs that modulate gene expression by interfering with translation or stability of mRNA transcripts in a sequence-specific manner. A total of 734 precursor and 996 mature miRNAs have so far been identified in the chicken genome. A number of these miRNAs are expressed in a cell type-specific manner, and understanding their function requires detailed examination of their expression in different cell types. We carried out deep sequencing of small RNA populations isolated from stimulated or transformed avian haemopoietic cell lines to determine the changes in the expression profiles of these important regulatory molecules during these biological events. There were significant changes in the expression of a number of miRNAs, including miR-155, in chicken B cells stimulated with CD40 ligand. Similarly, avian leukosis virus (ALV)-transformed DT40 cells also showed changes in miRNA expression in relation to the naive cells. Embryonic stem cell line BP25 demonstrated a distinct cluster of upregulated miRNAs, many of which were shown previously to be involved in embryonic stem cell development. Finally, chicken macrophage cell line HD11 showed changes in miRNA profiles, some of which are thought to be related to the transformation by v-myc transduced by the virus. This work represents the first publication of a catalog of microRNA expression in a range of important avian cells and provides insights into the potential roles of miRNAs in the hematopoietic lineages of cells in a model non-mammalian species.
Zohari S, Munir M (2013)

Avian paramyxoviruses serotype 1 to 10

Mononegaviruses of veterinary importance. Volume I: Pathobiology and molecular diagnosis (edited by M Munir, CABI), 15-37
Publisher’s version: http://dx.doi.org/10.1079/9781780641799.0015

Abstract

This chapter discusses the up-to-date literature on historical distribution, virus and disease, classification, viral replication, pathogenesis, clinical signs, gross lesions, disease transmission, other avian paramyxovirus serotypes and laboratory diagnosis of Avian paramyxoviruses in livestock, horses and pets.
Paton D J, King D P (2013)

Diagnosis of foot-and-mouth disease

Developments in Biologicals 135, 117-123
Publisher’s version: http://dx.doi.org/10.1159/000325267

Abstract

Foot-and-mouth disease virus (FMDV) exists as multiple serotypes and strains that infect a range of cloven-hoofed animals with variable severity. Clinical diagnosis reinforced by diagnostic tests support timely intervention, whilst virus characterisation helps trace routes of spread and select appropriate vaccine strains. To speed up and simplify diagnosis, penside tests have recently been developed. Serology is used to identify undisclosed infection and substantiate freedom from infection and specific tests are needed to detect infected animals in vaccinated populations. Serology is also used to estimate post-vaccinal population immunity. Contingency plans are required to enable countries to scale up diagnosis at short notice. Improvements are needed in preclinical and penside diagnosis and in our ability to model vaccine effectiveness.
Perez de Diego A C, Sanchez-Cordon P J, Pedrera M, Martinez-Lopez B, Gomez-Villamandos J C, Sanchez-Vizcaino J M (2013)

The use of infrared thermography as a non-invasive method for fever detection in sheep infected with bluetongue virus

Veterinary Journal 198 (1), 182-186
Publisher’s version: http://dx.doi.org/10.1016/j.tvjl.2013.07.013

Abstract

Fever, which is closely linked to viraemia, is considered to be both the main and the earliest clinical sign in sheep infected with bluetongue virus (BTV). The aim of this study was to evaluate the potential use of infrared thermography (IRT) for early detection of fever in sheep experimentally infected with bluetongue virus serotype 1 (BTV-1) and serotype 8 (BTV-8). This would reduce animal stress during experimental assays and assist in the development of a screening method for the identification of fever in animals suspected of being infected with BTV. Rectal and infrared eye temperatures were collected before and after BTV inoculation. The two temperature measures were positively correlated (r = 0.504, P
Peroval M Y, Boyd A C, Young J R, Smith A L (2013)

A critical role for MAPK signalling pathways in the transcriptional regulation of toll like receptors

PLoS ONE 8 (2), e51243
Publisher’s version: http://dx.doi.org/10.1371/journal.pone.0051243

Abstract

Toll-like Receptors (TLR) are phylogenetically conserved transmembrane proteins responsible for detection of pathogens and activation of immune responses in diverse animal species. The stimulation of TLR by pathogen-derived molecules leads to the production of pro-inflammatory mediators including cytokines and nitric oxide. Although TLR-induced events are critical for immune induction, uncontrolled inflammation can be life threatening and regulation is a critical feature of TLR biology. We used an avian macrophage cell line (HD11) to determine the relationship between TLR agonist-induced activation of inflammatory responses and the transcriptional regulation of TLR. Exposure of macrophages to specific TLR agonists induced upregulation of cytokine and nitric oxide pathways that were inhibited by blocking various components of the TLR signalling pathways. TLR activation also led to changes in the levels of mRNA encoding the TLR responsible for recognising the inducing agonist (cognate regulation) and cross-regulation of other TLR (non-cognate regulation). Interestingly, in most cases, regulation of TLR mRNA was independent of NF?B activity but dependent on one or more of the MAPK pathway components. Moreover, the relative importance of ERK, JNK and p38 was dependent upon both the stimulating agonist and the target TLR. These results provide a framework for understanding the complex pathways involved in transcriptional regulation of TLR, immune induction and inflammation. Manipulation of these pathways during vaccination or management of acute inflammatory disease may lead to improved clinical outcome or enhanced vaccine efficacy.

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