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

There were a total of 2609 results for your search.
Meyers G, Ege A, Fetzer C, von Freyburg M, Elbers K, Carr V, Prentice H, Charleston B, Schurmann E M (2007)

Bovine viral diarrhea virus: prevention of persistent fetal infection by a combination of two mutations affecting Erns RNase and Npro protease

Journal of Virology 81 (7), 3327-3338
Publisher’s version: http://dx.doi.org/10.1128/JVI.02372-06

Abstract

Different genetically engineered mutants of bovine viral diarrhea virus (BVDV) were analyzed for the ability to establish infection in the fetuses of pregnant heifers. The virus mutants exhibited either a deletion of the overwhelming part of the genomic region coding for the N-terminal protease Npro, a deletion of codon 349, which abrogates the RNase activity of the structural glycoprotein Erns, or a combination of both mutations. Two months after infection of pregnant cattle with wild-type virus or either of the single mutants, the majority of the fetuses contained virus or were aborted or found dead in the uterus. In contrast, the double mutant was not recovered from fetal tissues after a similar challenge, and no dead fetuses were found. This result was verified with a nonrelated BVDV containing similar mutations. After intrauterine challenge with wild-type virus, mutated viruses, and cytopathogenic BVDV, all viruses could be detected in fetal tissue after 5, 7, and 14 days. Type 1 interferon (IFN) could be detected in fetal serum after challenge, except with wild-type noncytopathogenic BVDV. On days 7 and 14 after challenge, the largest quantities of IFN in fetal serum were induced by the Npro and RNase-negative double mutant virus. The longer duration of fetal infection with the double mutant resulted in abortion. Therefore, for the first time, we have demonstrated the essential role of both Npro and Erns RNase in blocking interferon induction and establishing persistent infection by a pestivirus in the natural host.
O'Sullivan D M, Sander C, Shorten R J, Gillespie S H, Hill A V S, McHugh T D, McShane H, Tchilian E Z (2007)

Evaluation of liquid culture for quantitation of Mycobacterium tuberculosis in murine models

Vaccine 25 (49), 8203-8205
Publisher’s version: http://dx.doi.org/10.1016/j.vaccine.2007.09.065

Abstract

Quantitation of bacterial load in tissues is essential for experimental investigation of Mycobacterium tuberculosis infection and immunity. We have used an automated liquid culture system to determine the number of colony forming units (CFU) in murine tissues and compared the results to those obtained by conventional plating on Middlebrook agar. There is an overall good correlation between results obtained by the two methods. Although less consistency and more contamination was observed in the automated liquid culture, the method is more sensitive, less labour intensive and allows the processing of large numbers of samples. (C) 2007 Elsevier Ltd. All fights reserved.
Parida S, Fleming L, Gibson D, Hamblin P A, Grazioli S, Brocchi E, Paton D J (2007)

Bovine serum panel for evaluating foot-and-mouth disease virus nonstructural protein antibody tests

Journal of Veterinary Diagnostic Investigation 19 (5), 539-544
Publisher’s version: http://dx.doi.org/10.1177/104063870701900513

Abstract

A panel of 36 sera has been assembled from experimental cattle that had been infected by inoculation or contact exposure with 4 serotypes of foot-and-mouth disease virus (FMDV) with or without prior vaccination. Virus replication and persistence had been characterized in all of the animals. The proportion of the sera scored positive by 5 tests for antibodies to the nonstructural proteins of FMDV varied, suggesting that the panel can discriminate between the sensitivity with which such tests are able to identify infected cattle. Use of this panel will help in assessment of new tests and quality control of existing methods.
Parida S, Fleming L, Oh Y, Mahapatra M, Hamblin P, Gloster J, Doel C, Gubbins S, Paton D J (2007)

Reduction of foot-and-mouth disease (FMD) virus load in nasal excretions, saliva and exhaled air of vaccinated pigs following direct contact challenge

Vaccine 25 (45), 7806-7817
Publisher’s version: http://dx.doi.org/10.1016/j.vaccine.2007.08.058

Abstract

In future, a policy of “vaccinate-to-live” may be included in the repertoire of foot-and-mouth disease (FMD) control measures and in support of this approach, we have investigated the hypothesis that vaccine-induced reduction in virus replication and excretion from pigs can be correlated to the severity of clinical signs of FMD by measuring excretion of virus in natural secretions and aerosols. The other aims of this study were to verify the existence of sub-clinical infection in vaccinated pigs, to evaluate the correlation between this and seroconversion to foot-and-mouth disease virus (FMDV) non-structural protein antibodies and to re-examine the occurrence of FMDV persistence in the oro-pharynx of pigs. Therefore, pigs were vaccinated (O1 Manisa) and challenged (O1 UKG) in a manner calculated to produce a broad range of clinical outcomes and were monitored for a minimum of another 33 days post-challenge. Eighty-one percent of the early (10 days vaccinated) challenged pigs and 25% of the late (29 days vaccinated) challenged pigs were clinically infected and all other vaccinated pigs were sub-clinically infected. Although vaccination could not provide complete clinical or virological protection, it reduced the severity of the disease, virus excretion and production of non-structural FMDV antibodies in vaccinated and subsequently infected pigs. As hypothesised, vaccine-induced reduction of virus replication and excretion was found to be correlated to the severity of clinical disease. RNA copies, but no live virus was detected from the pharyngeal and soft palate tissues of a minority of vaccinated and infected pigs beyond the acute stage of the infection.
Parida S, Mahapatra M, Kumar S, Das S C, Baron M D, Anderson J, Barrett T (2007)

Rescue of a chimeric rinderpest virus with the nucleocapsid protein derived from peste-des-petits-ruminants virus: use as a marker vaccine

Journal of General Virology 88, 2019-2027
Publisher’s version: http://dx.doi.org/10.1099/vir.0.82913-0

Abstract

The nucleocapsid (N) protein of all morbilliviruses has a highly conserved central region that is thought to interact with and encapsidate the viral RNA. The C-terminal third of the N protein is highly variable among morbilliviruses and is thought to be located on the outer surface and to be available to interact with other viral proteins such as the phosphoprotein, the polymerase protein and the matrix protein. Using reverse genetics, a chimeric rinderpest virus (RPV)/peste-des-petits-ruminants virus (PPRV) was rescued in which the RPV N gene open reading frame had been replaced with that of PPRV (RPV–PPRN). The chimeric virus maintained efficient replication in cell culture. Cattle vaccinated with this chimeric vaccine showed no adverse reaction and were protected from subsequent challenge with wild-type RPV, indicating it to be a safe and efficacious vaccine. The carboxyl-terminal variable region of the rinderpest N protein was cloned and expressed in Escherichia coli. The expressed protein was used to develop an indirect ELISA that could clearly differentiate between RPV- and PPRV-infected animals. The possibility of using this virus as a marker vaccine in association with a new diagnostic ELISA in the rinderpest eradication programme is discussed.
Pedrera M, Sanchez-Cordon P J, Romero-Trevejo J L, Raya A I, Nunez A, Gomez-Villamandos J C (2007)

Cytokine expression in paraffin wax-embedded tissues from conventional calves

Journal of Comparative Pathology 136 (4), 273-278
Publisher’s version: http://dx.doi.org/10.1016/j.jcpa.2007.02.002

Abstract

The cross-reactivity of antibodies against human tumour necrosis factor (TNF) alpha, interleukin (IL)-1 alpha, IL-1 beta and porcine IL-6, and the distribution of immunolabelled cells were evaluated on paraffin wax-embedded tissues from five healthy calves. The tissues were fixed in 10% buffered formalin or Bouin's solution and processed for structural studies and immunohistochemical studies by the avidin-biotin-peroxidase technique. Bouin's solution proved to be the more suitable fixative and Tween 20 the most effective antigen unmasking technique for increasing detectable antigenicity. Constitutive expression of TNF alpha, IL-1 alpha, IL-1 beta and IL-6 by different cell populations, mainly macrophage-like cells, was detected. Lymphoid organs displayed a higher presence of immunolabelled cells than did lung, liver or kidneys TNF alpha and IL-1 alpha appeared as the predominant cytokines, especially in the gut-associated lymphoid tissue of the ileum and in the regional mesenteric lymph nodes. The results will facilitate investigation of the role of these cytokine-producing cells in inflammatory disease processes in calves.
Perkins J, Parida S, Clavijo A (2007)

Use of a standardized bovine serum panel to evaluate a multiplexed nonstructural protein antibody assay for serological surveillance of foot-and-mouth disease

Clinical and Vaccine Immunology 14 (11), 1472-1482
Publisher’s version: http://dx.doi.org/10.1128/CVI.00227-07

Abstract

Liquid array technology has previously been used to show proof of principle of a multiplexed nonstructural protein serological assay to differentiate foot-and-mouth disease virus-infected and vaccinated animals. The current multiplexed assay consists of synthetically produced peptide signatures 3A, 3B, and 3D and the recombinant protein signature 3ABC in combination with four controls. To determine the diagnostic specificity of each signature in the multiplex, the assay was evaluated against a naive population (n = 104) and a vaccinated population (n = 94). Subsequently, the multiplexed assay was assessed by using a panel of bovine sera generated by the World Reference Laboratory for foot-and-mouth disease in Pirbright, United Kingdom. This serum panel has been used to assess the performance of other singleplex enzyme-linked immunosorbent assay (ELISA)-based nonstructural protein antibody assays. The 3ABC signature in the multiplexed assay showed performance comparable to that of a commercially available nonstructural protein 3ABC ELISA (Cedi test), and additional information pertaining to the relative diagnostic sensitivity of each signature in the multiplex was acquired in one experiment. The encouraging results of the evaluation of the multiplexed assay against a panel of diagnostically relevant samples promote further assay development and optimization to generate an assay for routine use in foot-and-mouth disease serological surveillance.
Phuc H K, Andreasen M H, Burton R S, Vass C, Epton M J, Pape G, Fu G L, Condon K C, Scaife S, Donnelly C A, Coleman P G, White-Cooper H, Alphey L (2007)

Late-acting dominant lethal genetic systems and mosquito control

BMC Biology 5, e11
Publisher’s version: http://dx.doi.org/10.1186/1741-7007-5-11

Abstract

Background: Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality. Results: We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality. Conclusion: Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease control.

Pillai M R, Lefevre E A, Carr B V, Charleston B, O'Grady P (2007)

Workshop cluster 1, a gammadelta T cell specific receptor is phosphorylated and down regulated by activation induced Src family kinase activity

Molecular Immunology 44 (7), 1691-1703
Publisher’s version: http://dx.doi.org/10.1016/j.molimm.2006.08.009

Abstract

Workshop cluster 1+ gamma delta (WC1+??) T cells have been shown to play important roles in the immune response to infections. WC1 is a transmembrane glycoprotein, uniquely expressed on the surface of ?? T cells of ruminants and pigs. A role for WC1 in inducing a reversible growth arrest of ?? T cells has been previously demonstrated. WC1-induced growth inhibition has been shown to be overcome following ?? T cell activation with Concanavalin A (Con A). However, molecular mechanism(s) by which WC1 signalling might be modulated following activation have not been elucidated. In this paper we show that Con A activation of bovine lymphocytes induces the tyrosine phosphorylation of WC1 in a Src-family kinase-dependent manner. Src family kinases also phosphorylated WC1 in a COS-7 co-transfection system. Furthermore, a glutathione-S-transferase (GST)-WC1 cytoplasmic domain fusion protein was directly phosphorylated by recombinant Lck (rLck) in vitro. The Y1303 of WC1 was identified by mutational analysis as the only one of the five WC1 tyrosine residues to be critical for Src family phosphorylation. The importance of activation-induced Src family activity for WC1 function was investigated with the Src-family specific inhibitor PP2. These studies show that the surface levels of WC1 are down regulated in a Src-family-dependent manner following activation of bovine lymphocytes. Down regulation of surface WC1 was accompanied by a Src-family-dependent accumulation of intracellular WC1. These data show that WC1 is modulated by activation-induced tyrosine phosphorylation thus providing a new insight into the signalling mechanisms by which WC1 and ?? T cell activation are regulated in this important and unique cell population.

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