Publications

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

There were a total of 2599 results for your search.
Paton D J, King D P (2013)

Diagnosis of foot-and-mouth disease

Developments in Biologicals 135, 117-123

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.

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

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.

Abstract

Peste-des-petits ruminants virus (PPRV) is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV) and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d’Ivoire ’89 (CI/89) and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis.

Abstract

Picornaviruses are small RNA viruses, responsible for important human and animal diseases for example polio, some forms of the common cold and foot-and-mouth disease. Safe and effective picornavirus vaccines could in principle be produced from recombinant virus-like particles, which lack the viral genome and so cannot propagate. However the synthesis of stable forms of such particles at scale has proved very difficult. Two key problems have been that a protease required for the proper processing of the polyprotein precursor is toxic for host cells and the empty recombinant particles tend to be physically unstable in comparison to virus particles containing nucleic acid. This is particularly true in the case of Foot-and-Mouth Disease Virus (FMDV). Here we report the production and evaluation of a novel vaccine against FMDV that addresses both of these shortcomings. Importantly, the strategies we have devised to produce improved FMDV vaccines can be directly applied to viruses pathogenic for humans
Porta C, Xu X, Loureiro S, Paramasivam S, Ren J, Al-Khalil T, Burman A, Jackson T, Belsham G J, Curry S, Lomonossoff G P, Parida S, Paton D, Li Y, Wilsden G, Ferris N, Owens R, Kotecha A, Fry E, Stuart D I, Charleston B, Jones I M (2013)

Efficient production of foot-and-mouth disease virus empty capsids in insect cells following down regulation of 3C protease activity

Journal of Virological Methods 187 (2), 406-412

Abstract

Foot-and-mouth disease virus (FMDV) is a significant economically and distributed globally pathogen of Artiodactyla. Current vaccines are chemically inactivated whole virus particles that require large-scale virus growth in strict bio-containment with the associated risks of accidental release or incomplete inactivation. Non-infectious empty capsids are structural mimics of authentic particles with no associated risk and constitute an alternate vaccine candidate. Capsids self-assemble from the processed virus structural proteins, VP0, VP3 and VP1, which are released from the structural protein precursor P1-2A by the action of the virus-encoded 3C protease. To date recombinant empty capsid assembly has been limited by poor expression levels, restricting the development of empty capsids as a viable vaccine. Here expression of the FMDV structural protein precursor P1-2A in insect cells is shown to be efficient but linkage of the cognate 3C protease to the C-terminus reduces expression significantly. Inactivation of the 3C enzyme in a P1-2A-3C cassette allows expression and intermediate levels of 3C activity resulted in efficient processing of the P1-2A precursor into the structural proteins which assembled into empty capsids. Expression was independent of the insect host cell background and leads to capsids that are recognised as authentic by a range of anti-FMDV bovine sera suggesting their feasibility as an alternate vaccine.
Ramilo D, Garros C, Mathieu B, Benedet C, Allene X, Silva E, Alexandre-Pires G, Da Fonseca I P, Carpenter S, Radrova J, Delecolle J-C (2013)

Description of Culicoides paradoxalis sp nov from France and Portugal (Diptera: Ceratopogonidae)

Zootaxa 3745 (2), 243-256

Abstract

A new species, Culicoides paradoxalis Ramilo and Delecolle (Diptera: Ceratopogonidae), is described from specimens collected in France (Corsica and southeast region) and Portugal. This species resembles Culicoides lupicaris Downes and Kettle, and can be distinguished from this species and from Culicoides newsteadi Austen by its wing pattern, in addition to the absence of spines on the tarsomere 4 of female mid leg. In male, the presence of two appendices on the sternite 9 together with the absence of sensilla coeloconica on the flagellomere 11 is also useful to distinguish these three species. Separation from other members of the Culicoides subgenus is confirmed by the analysis of the Cytochrome Oxidase I (COI) mitochondrial marker.
Rautenschlein S, Munir M, Seal B S (2013)

Avian metapneumoviruses

Mononegaviruses of veterinary importance. Volume I: Pathobiology and molecular diagnosis (edited by M Munir, CABI), 185-198

Abstract

This chapter discusses the historical distribution of Avian metapneumoviruses (aMPV), molecular biology of aMPV isolates, pathobiology of aMPV, diagnostics and prevention of aMPV disease in turkey and poultry.

Abstract

Objective-To compare pathological changes and viral antigen distribution in tissues of calves with and without preexisting subclinical bovine viral diarrhea virus (BVDV) infection following challenge with 'bovine herpesvirus-1 (BHV-1). Animals-24 Friesian calves. Procedures-12 calves were inoculated intranasally with noncytopathic BVDV-la; 12 days later, 10 of these calves were challenged intranasally with BHV-1 subtype 1. Two calves were euthanized before and 1, 2, 4, 7 or 14 days after BHV-1 inoculation. Another 10 calves were inoculated intranasally with BHV-1 only and euthanized 1, 2, 4, 7, or 14 days later. Two calves were inoculated intranasally with virus-free tissue culture fluid and euthanized as negative controls. Pathological changes and viral antigen distribution in various tissue samples from calves with and without BVDV infection (all of which had been experimentally inoculated with BHV-1) were compared. Results-Following BHV-1 challenge, calves with preexisting subclinical BVDV infection had earlier development of more severe inflammatory processes and, consequently, more severe tissue lesions (limited to lymphoid tissues and respiratory and digestive tracts) and greater dissemination of BHV-1, compared with calves without preexisting BVDV infection. Moreover, coinfected calves had an intense lymphoid depletion in the Peyer patches of the ileum as well as the persistence of BVDV in target organs and the reappearance of digestive tract changes during disease progression. Conclusions and Clinical Relevance-In calves, preexisting infection with BVDV facilitated the establishment of BHV-1 infection, just as the presence of BHV-1 favors BVDV persistence, thereby synergistically potentiating effects of both viruses and increasing the severity of the resultant clinical signs.

Abstract

Resistance to respiratory disease in cattle requires host defense mechanisms that protect against pathogens which have evolved sophisticated strategies to evade them, including an altered function of pulmonary macrophages (M phi s) or the induction of inflammatory responses that cause lung injury and sepsis. The aim of this study was to clarify the mechanisms responsible for vascular changes occurring in the lungs of calves infected with bovine viral diarrhea virus (BVDV) and challenged later with bovine herpesvirus type 1 (BHV-1), evaluating the role of M phi s in the development of pathological lesions in this organ. For this purpose, pulmonary lesions were compared between co-infected calves and healthy animals inoculated only with BHV-1 through immunohistochemical (MAC387, TNF alpha, IL-1 alpha, iNOS, COX-2 and Factor-VIII) and ultrastructural studies. Both groups of calves presented important vascular alterations produced by fibrin microthrombi and platelet aggregations within the blood vessels. These findings were earlier and more severe in the co-infected group, indicating that the concomitance of BVDV and BHV-1 in the lungs disrupts the pulmonary homeostasis by facilitating the establishment of an inflammatory and procoagulant environment modulated by inflammatory mediators released by pulmonary M phi s. In this regard, the co-infected calves, in spite of presenting a greater number of IM phi s than single-infected group, show a significant decrease in iNOS expression coinciding with the presence of more coagulation lesions. Moreover, animals pre-inoculated with BVDV displayed an alteration in the response of pro-inflammatory cytokines (TNF alpha and IL-1), which play a key role in activating the immune response, as well as in the local cell-mediated response.

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