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

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Arzt J, Juleff N, Zhang Z, Rodriguez L L (2011)

The pathogenesis of foot-and-mouth disease I: viral pathways in cattle. (Review)

Transboundary and Emerging Diseases 58 (4), 291-304
Publisher’s version: http://dx.doi.org/10.1111/j.1865-1682.2011.01204.x

Abstract

In 1898, foot-and-mouth disease (FMD) earned a place in history as the first disease of animals shown to be caused by a virus. Yet, despite over a century of active investigation and elucidation of many aspects of FMD pathogenesis, critical knowledge about the virus-host interactions is still lacking. The aim of this review is to provide a comprehensive overview of FMD pathogenesis in cattle spanning from the earliest studies to recently acquired insights emphasizing works which describe animals infected by methodologies most closely resembling natural infection (predominantly aerosol or direct/indirect contact). The three basic phases of FMD pathogenesis in vivo will be dissected and characterized as: (i) pre-viraemia characterized by infection and replication at the primary replication site(s), (ii) sustained viraemia with generalization and vesiculation at secondary infection sites and (iii) post-viraemia/convalescence including resolution of clinical disease that may result in long-term persistent infection. Critical evaluation of the current status of understanding will be used to identify knowledge gaps to guide future research efforts.
Badr G, Lefevre E A, Mohany M (2011)

Thymoquinone inhibits the CXCL12-induced chemotaxis of multiple myeloma cells and increases their susceptibility to Fas-mediated apoptosis

PLoS One 6 (9), e23741
Publisher’s version: http://dx.doi.org/10.1371/journal.pone.0023741

Abstract

In multiple myeloma (MM), malignant plasma cells reside in the bone marrow, where they accumulate in close contact with stromal cells. The mechanisms responsible for the chemotaxis of malignant plasma cells are still poorly understood. Thus, we investigated the mechanisms involved in the chemotaxis of MDN and XG2 MM cell lines. Both cell lines strongly expressed CCR9, CXCR3 and CXCR4 chemokine receptors but only migrated toward CXCL12. Activation of CXCR4 by CXCL12 resulted in the association of CXCR4 with CD45 and activation of PLC beta 3, AKT, RhoA, I kappa B alpha and ERK1/2. Using siRNA-silencing techniques, we showed CD45/CXCR4 association is essential for CXCL12-induced migration of MM cells. Thymoquinone (TQ), the major active component of the medicinal herb Nigella sativa Linn, has been described as a chemopreventive and chemotherapeutic compound. TQ treatment strongly inhibited CXCL12-mediated chemotaxis in MM cell lines as well as primary cells isolated from MM patients, but not normal PBMCs. Moreover, TQ significantly down-regulated CXCR4 expression and CXCL12-mediated CXCR4/CD45 association in MM cells. Finally, TQ also induced the relocalization of cytoplasmic Fas/CD95 to the membrane of MM cells and increased CD95-mediated apoptosis by 80%. In conclusion, we demonstrate the potent anti-myeloma activity of TQ, providing a rationale for further clinical evaluation.
Baigent S J, Smith L P, Petherbridge L J, Nair V K (2011)

Differential quantification of cloned CVI988 vaccine strain and virulent RB-1B strain of Marek's disease viruses in chicken tissues, using real-time PCR

Research in Veterinary Science 91 (1), 167-174
Publisher’s version: http://dx.doi.org/10.1016/j.rvsc.2010.08.002

Abstract

The 'gold standard' vaccine against Marek's disease in poultry is the CVI988/Rispens virus, which is not easily distinguishable, antigenically or genetically, from virulent Marek's disease herpesvirus. Accurate differential measurement of the CVI988 vaccine and virulent viruses is important to investigate mechanisms of vaccinal protection. Minimal sequence differences between CVI988 and virulent MDV strains restrict the application of molecular diagnostic methods such as real-time PCR to distinguish between these viruses. The use of bacterial-artificial-chromosome (BAC) cloned CVI988 virus, which carries the BAC vector sequences in place of the U(s)2 gene, allows its differential quantification from virulent strains using real-time PCR assays that target the BAC vector sequence and the U(s)2 gene respectively. These novel assays allowed investigation of replication of both serotype-1 vaccine virus (cloned CVI988) and challenge virus (RB-1B strain) in tissues of individual chickens in an experimental vaccination-challenge model of Marek's disease.
Balu S, Rothwell L, Kaiser P (2011)

Production and characterisation of monoclonal antibodies specific for chicken interleukin-12

Veterinary Immunology and Immunopathology 140 (1-2), 140-146
Publisher’s version: http://dx.doi.org/10.1016/j.vetimm.2010.11.009

Abstract

Using genetic immunisation of mice, we produced antibodies against chicken interleukin-12p40 (chIL-12p40), also known as IL-12 beta. After a final injection with a recombinant chIL-12p40 protein, several stable hybridoma cell lines were established which secreted monoclonal antibodies (mAbs) to this component of the heterodimeric IL-12 cytokine. Specific binding of three of the mAbs to COS-7 cell-derived recombinant chIL-12p40 and the chIL-12p70 heterodimer was demonstrated in an indirect ELISA, and in dot blots. Two of the mAbs were used to develop a capture ELISA, suitable for detecting both recombinant protein (chIL-12p40 and the heterodimeric p70 protein) and native chIL-12. The mAbs were further characterised to show utility in immunocytochemistry.
Banyard A C, Tiwari A, Barrett T (2011)

Morbillivirus infection in pilot whales: strict protein requirement drives genetic conservation

Archives of Virology 156 (10), 1853-1859
Publisher’s version: http://dx.doi.org/10.1007/s00705-011-1042-8

Abstract

Morbillivirus infection of marine mammals has been documented across all of the world's oceans. Whilst infection is generally demonstrated using a variety of histopathological and serological techniques, where possible, the use of molecular techniques is being used to enable accurate genetic typing of virus strains through sequence analysis. Here, we present genetic data from dolphins and pilot whales affected by morbillivirus infection in the recent outbreak in the Mediterranean Sea during a six-month period from the end of October 2006 to April 2007. To date, very few studies have looked at characterizing outbreaks of morbillivirus infections in whale species at the molecular level. Here, we provide a full sequence for the haemagglutinin (H) gene from material derived from both a dolphin and a pilot whale from the 2007 outbreak in the Mediterranean Sea and show this virus to be 100% identical across the region analysed. Furthermore, we compare partial sequence data from the nucleocapsid (N) gene of the pilot whale material with previously published data and show evidence for strong protein conservation between these different isolates. Finally, we discuss the current classification of cetacean morbilliviruses as a single species.
Baron M D (2011)

Rinderpest and peste des petits ruminants viruses

The Biology of Paramyxoviruses (edited by S. K. Samal, Caister Academic Press), 293-339
Publisher’s version: https://www.caister.com/paramyxoviruses

Abstract

In terms of their impact on livestock, and therefore on human well-being and development, rinderpest virus (RPV) and peste des petits ruminants virus (PPRV) are two of the most important members of the paramyxovirus family. RPV, the cause of the most feared of all cattle diseases, now appears to have been eradicated; however, over the past 20 years, PPRV has increased its global distribution through most of sub-Saharan and North Africa, the Middle East, the Indian sub-continent and eastwards into Tibet. While most scientific effort has been focused on developing means of control of the diseases, effort in a small number of laboratories has thrown light on the detailed molecular biology of the viruses, providing information on those areas in which they are the same as, or differ from, other members of the same genus. Such findings have highlighted how important it is to understand the way that these viruses are restricted in the range of organisms in which they will cause disease, an understanding that will become increasingly important with the success in eradicating these diseases on a local and global level.

Baron M D, Parida S, Oura C A L (2011)

Peste des petits ruminants: a suitable candidate for eradication?

Veterinary Record 169 (1), 16-21
Publisher’s version: http://dx.doi.org/10.1136/vr.d3947

Abstract

This year will see the final announcement, accompanied by much justifiable celebration, of the eradication from the wild of rinderpest, the 'cattle plague' that has been with us for so many centuries. The only known rinderpest virus (RPV) remaining is in a relatively small number of laboratories around the world, and in the stockpiles of vaccine held on a precautionary basis. As we mark this achievement, only the second virus ever eradicated through human intervention, it seems a good time to look at rinderpest's less famous cousin, peste des petits ruminants ('the plague of small ruminants') and assess if it should, and could, also be targeted for global eradication.
Bartram D J, Heasman L, Batten C A, Oura C A, Plana-Duran J, Yuen H M, Wylie A D (2011)

Neutralising antibody responses in cattle and sheep following booster vaccination with two commercial inactivated bluetongue virus serotype 8 vaccines

Veterinary Journal 188 (2), 193-196
Publisher’s version: http://dx.doi.org/10.1016/j.tvjl.2010.04.001

Abstract

Cattle and sheep that had received a primary course of vaccination with an inactivated bluetongue virus serotype 8 (BTV-8) vaccine were booster vaccinated 6 or 12 months later with the homologous vaccine or an alternative inactivated BTV-8 vaccine and neutralising antibody responses were determined. Antibody titres to the alternative vaccine were significantly higher than to the homologous vaccine (P = 0.013) in cattle. There was no significant difference between the antibody responses to alternative and homologous vaccines in sheep. These data indicate that cattle and sheep primed with one inactivated BTV-8 vaccine may be effectively boosted with an alternative commercial inactivated BTV-8 vaccine
Batten C A, Banyard A C, King D P, Henstock M R, Edwards L, Sanders A, Buczkowski H, Oura C C L, Barrett T (2011)

A real time RT-PCR assay for the specific detection of Peste des petits ruminants virus.

Journal of Virological Methods 171 (2), 401-404
Publisher’s version: http://dx.doi.org/10.1016/j.jviromet.2010.11.022

Abstract

Peste des petits ruminants virus (PPRV) causes a devastating disease of small ruminants present across much of Africa and Asia. Recent surveillance activities and phylogenetic analyses have suggested that the virus is an emerging problem as it is now being detected in areas previously free of the disease. As such, the virus not only is threatening small ruminant production and agricultural stability in the developing world, but also poses an economic threat to livestock in the European Union (EU) through introduction from European Turkey and North Africa. This report describes the development of a high throughput, rapid, real time RT-PCR method for the sensitive and specific detection of PPRV using robotic RNA extraction. This assay targets the nucleocapsid (N) gene of PPRV and has been shown to detect all four genetic lineages of PPRV in tissues, ocular and nasal swabs and blood samples collected in the field. The lowest detection limit achieved was approximately 10 genome copies/reaction, making this assay an ideal tool for the sensitive and rapid detection of PPRV in diagnostic laboratories.
Batten C A, Edwards L, Bin-Tarif A, Henstock M R, Oura C A (2011)

Infection kinetics of epizootic haemorrhagic disease virus serotype 6 in Holstein-Friesian cattle

Veterinary Microbiology 154 (1-2), 23-28
Publisher’s version: http://dx.doi.org/10.1016/j.vetmic.2011.06.018

Abstract

Epizootic Haemorrhagic Disease virus serotype 6 (EHDV-6) has recently caused serious outbreaks of Epizootic Haemorrhagic Disease (EHD) on the edges of Europe, in Turkey, Israel and Morocco. The aim of this study was to assess the pathogenicity and infection kinetics of EHD in Holstein-Friesian cattle infected with the two distinct strains of EHDV-6 isolated from the recent Turkish and Moroccan outbreaks. Samples taken throughout the study were used to validate two recently developed diagnostic assays that detect EHDV antibodies and viral genome. Two groups of five Holstein-Friesian cattle were experimentally infected with either the Moroccan or the Turkish isolate of EHDV-6. Cattle in both groups remained clinically unaffected throughout the study, but displayed high levels of viral RNA and virus in their blood, confirming that sub-clinical infection of cattle is likely to play an important role in EHDV transmission. A recently developed and commercialised real-time RT-PCR assay detected viral RNA as early as 2 days post infection (dpi) in both infection studies and viral RNA persisted for the course of the study. Antibodies against EHDV were first detected by 9 dpi using a recently developed EHDV blocking ELISA and antibodies persisted up to the end of the study. All animals developed high levels of neutralising antibodies to EHDV-6, measured by a serum neutralisation test (SNT), with titres (log 10) ranging from 2.20 to 2.38 at the end of the study. Virus was isolated from the blood of infected animals from as early as 2 dpi up to 28 dpi.

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