Publications

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

There were a total of 2173 results for your search.
Waters R A, Wadsworth J, Mioulet V, Shaw A E, Knowles N J, Abdollahi D, Hassanzadeh R, Sumption K, King D P (2021)

Foot-and-mouth disease virus infection in the domestic dog (Canis lupus familiaris), Iran

BMC Veterinary Research 17 (1), 63

Abstract

Background: Foot-and-mouth disease (FMD) is a highly infectious viral disease, recognised to affect animals in the order Artiodactyla. The disease is rarely fatal in adult animals, however high mortality is associated with neonatal and juvenile infection.

Case presentation: Five puppies died after being fed lamb carcases, the lambs having died during an outbreak of FMD in Iran. Following a post-mortem examination, cardiac tissue from one of the dead puppies was subjected to virus isolation, antigen ELISA, real-time RT-PCR, sequencing and confocal microscopy to assess the presence and characteristics of any FMD virus. The virological and microscopic examination of the cardiac tissue provided evidence of FMD virus replication in the canine heart.

Conclusions: The data generated in this study demonstrate for the first time that FMD virus can internalise and replicate in dogs and may represent an epidemiologically significant event in FMD transmission, highlighting the dangers of feeding diseased animal carcases to other species. The reporting of this finding may also focus attention on similar disease presentations in dogs in FMD endemic countries allowing a better understanding of the prevalence of such events.

Abstract

Processing and packaging of herpesvirus genomic DNA is regulated by a packaging-associated terminase complex comprising of viral proteins pUL15, pUL28 and pUL33. Marek’s disease virus (MDV) homologs UL28 and UL33 showed conserved functional features with high sequence identity with the corresponding Herpes simplex virus 1 (HSV-1) homologs. As part of the investigations into the role of the UL28 and UL33 homologs of oncogenic MDV for DNA packaging and replication in cultured cells, we generated MDV mutant clones deficient in UL28 or UL33 of full-length MDV genomes. Transfection of UL28- or UL33-deleted BAC DNA into chicken embryo fibroblast (CEF) did not result either in the production of visible virus plaques, or detectable single cell infection after passaging onto fresh CEF cells. However, typical MDV plaques were detectable in CEF transfected with the DNA of revertant mutants where the deleted genes were precisely reinserted. Moreover, the replication defect of the UL28-deficient mutant was completely restored when fragment encoding the full UL28 gene was co-transfected into CEF cells. Viruses recovered from the revertant construct, as well as by the UL28 co-transfection, showed replication ability comparable with parental virus. Furthermore, the transmission electron microscopy study indicated that immature capsids were assembled without the UL28 expression, but with the loss of infectivity. Importantly, predicted three-dimensional structures of UL28 between MDV and HSV-1 suggests conserved function in virus replication. For the first time, these results revealed that both UL28 and UL33 are essential for MDV replication through regulating DNA cleavage and packaging.

Psifidi A, Kranis A, Rothwell L M, Bremner A, Russell K, Robledo D, Bush S J, Fife M, Hocking P M, Banos G, Hume D A, Kaufman J, Bailey R A, Avendano S, Watson K A, Kaiser P, Stevens M P (2021)

Quantitative trait loci and transcriptome signatures associated with avian heritable resistance to Campylobacter

Scientific Reports 11 (1), 1623

Abstract

Campylobacter is the leading cause of bacterial foodborne gastroenteritis worldwide. Handling or consumption of contaminated poultry meat is a key risk factor for human campylobacteriosis. One potential control strategy is to select poultry with increased resistance to Campylobacter. We associated high-density genome-wide genotypes (600K single nucleotide polymorphisms) of 3000 commercial broilers with Campylobacter load in their caeca. Trait heritability was modest but significant (h2 = 0.11 ± 0.03). Results confirmed quantitative trait loci (QTL) on chromosomes 14 and 16 previously identified in inbred chicken lines, and detected two additional QTLs on chromosomes 19 and 26. RNA-Seq analysis of broilers at the extremes of colonisation phenotype identified differentially transcribed genes within the QTL on chromosome 16 and proximal to the major histocompatibility complex (MHC) locus. We identified strong cis-QTLs located within MHC suggesting the presence of cis-acting variation in MHC class I and II and BG genes. Pathway and network analyses implicated cooperative functional pathways and networks in colonisation, including those related to antigen presentation, innate and adaptive immune responses, calcium, and renin-angiotensin signalling. While co-selection for enhanced resistance and other breeding goals is feasible, the frequency of resistance-associated alleles was high in the population studied and non-genetic factors significantly influenced Campylobacter colonisation.

Abstract

DNA vaccines are capable of inducing humoral and cellular immunity, and are important to control bovine herpesvirus 1 (BoHV-1), an agent of the bovine respiratory disease complex. In previous work, a DNA plasmid that encodes a secreted form of BoHV-1 glycoprotein D (pCIgD) together with commercial adjuvants provided partial protection against viral challenge of bovines. In this work, we evaluate new molecules that could potentiate the DNA vaccine. We show that a plasmid encoding a soluble CD40 ligand (CD40L) and the adjuvant MontanideTM GEL01 (GEL01) activate in vitro bovine afferent lymph dendritic cells (ALDCs). CD40L is a co-stimulating molecule, expressed transiently on activated CD4+ T cells and, to a lesser extent, on activated B cells and platelets. The interaction with its receptor, CD40, exerts effects on the presenting cells, triggering responses in the immune system. GEL01 was designed to improve transfection of DNA vaccines. We vaccinated cattle with: pCIgD; pCIgD-GEL01; pCIgD with GEL01 and CD40L plasmid (named pCIgD-CD40L-GEL01) or with pCIneo vaccines. The results show that CD40L plasmid with GEL01 improved the pCIgD DNA vaccine, increasing anti-BoHV-1 total IgGs, IgG1, IgG2 subclasses, and neutralizing antibodies in serum. After viral challenge, bovines vaccinated with pCIgD-GEL01-CD40L showed a significant decrease in viral excretion and clinical score. On the other hand, 80% of animals in group pCIgD-GEL01-CD40L presented specific anti-BoHV-1 IgG1 antibodies in nasal swabs. In addition, PBMCs from pCIgD-CD40L-GEL01 had the highest percentage of animals with a positive lymphoproliferative response against the virus and significant differences in the secretion of IFNγ and IL-4 by mononuclear cells, indicating the stimulation of the cellular immune response. Overall, the results demonstrate that a plasmid expressing CD40L associated with the adjuvant GEL01 improves the efficacy of a DNA vaccine against BoHV-1.

Edmans M, Adam M, Porter E, Vatzia E, Paudyal B, Martini V, Gubbins S, Francis O, Harley R, Thomas A, Burt R, Morgan S, Fuller A, Sewell A, Charleston B, Bailey M, Tchilian E (2021)

Magnitude and kinetics of T cell and antibody responses during H1N1pdm09 infection in outbred and inbred Babraham pigs.

Frontiers in Immunology 11, 604913

Abstract

We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize αβ, γδ T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to day 4-5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from day 5-6 post infection reaching a peak at 9-14 days. γδ cells produced cytokines ex vivo at day 2 post infection, while virus specific IFN-γ producing γδ T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4 and γδ cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyse immune responses to influenza.

Abstract

Peste des petits ruminants (PPR) is a transboundary viral disease that threatens more than 1.74 billion goats and sheep in approximately 70 countries globally. In 2015, the international community set the goal of eradicating PPR by 2030, and, since then, Food and Agriculture Organization of the United Nations (FAO) and World Organization for Animal Health (OIE) have jointly developed and implemented the Global Control and Eradication Strategy for PPR. Here, data from the United Nations Food and Agriculture Organization Statistical Database (FAOSTAT), the OIE World Animal Health Information System (WAHIS), Regional Roadmap Meetings, and countries’ responses to PPR Monitoring and Assessment Tool (PMAT) questionnaires were analyzed to inform on current progress towards PPR eradication. OIE recorded the use of over 333 million doses of vaccine in 12 countries from 2015 to 2018, 41.8% of which were used in Asia and 58.2% in Africa. Between 2015 and 2019, a total of 12,757 PPR outbreaks were reported to OIE: 75.1% in Asia, 24.8% in Africa, and 0.1% in Europe. The number of global outbreaks in 2019 fell to 1218, compared with 3688 in 2015. Analysis of vaccine use and PPR outbreaks in countries indicates that disease control strategies, particularly vaccination campaigns and vaccine distribution strategies, still require scientific evaluation. It is imperative that vaccination is undertaken based on the epidemiology of the disease in a region and is coordinated between neighboring countries to restrict transboundary movements. Strengthening surveillance and post-vaccination sero-monitoring at the national level is also essential. The PPR vaccine stock/bank established by FAO, OIE, and other partners have improved the quality assurance and supply of vaccines. However, to achieve PPR eradication, filling the funding gap for vaccination campaigns and other program activities will be critical.

Abstract

While wing form is known to differ between males and females of the genus Culicoides (Latreille, 1809), detailed studies of sexual dimorphism are lacking. In this study we analyze sex-specific differences in the wing form of five species of the subgenus Avaritia (Fox, 1955) using geometric morphometrics and comparative phylogenetic methods. Our results confirm the existence of marked sexual dimorphism in the wing form of the studied species and reveal for the first time that while there is a shared general pattern of sexual shape dimorphism within the subgenus, sexual size dimorphism and particular features of sexual shape dimorphism differ among species. Sexual shape dimorphism was found to be poorly associated to size and the evolutionary history of the species. The tight association of sexual shape dimorphism with aspect ratio suggests that the shape of the wing is optimized for the type of flight of each sex, i.e. dispersal flight in females vs aerobatic flight in males. Moreover, the fact that interspecific shape differences are greater and more strongly associated to aspect ratio in males than in females might be indicating that in males the selective pressures affecting flight performance characteristics are more heterogeneous and/or stronger than in females among the studied species. 

Leftwich P T, Spurgin L G, Harvey-Samuel T, Thomas C J E, Paladino L C, Edgington M P, Alphey L (2021)

Genetic pest management and the background genetics of release strains

Philosophical Transactions of the Royal Society of London B Biological Sciences 376 (1818), 20190805

Abstract

Genetic pest management (GPM) methods involve releasing modified versions of a pest species to mate with wild pests in the target area. Proposed for a wide range of applications in public health, agriculture and conservation, most progress has been made with pest insects. Offspring of the released modified insects and wild pests carry the modification-which might be transgenes, artificially introduced Wolbachia or genetic damage from radiation, for example-but they also carry a complete haploid genome from their laboratory-reared parent, as well as one from their wild parent. Unless these F1 hybrids are completely unable to reproduce, further mating will lead to introgression of DNA sequences from the release strain into the wild population. We discuss issues around strain selection and the potential consequences of such introgression. We conclude that such introgression is probably harmless in almost all circumstances, and could, in theory, provide specific additional benefits to the release programme. We outline population monitoring approaches that could be used, going forward, to determine how background genetics may affect GPM.

This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.

Abstract

The insect sex determination and the intimately linked dosage compensation pathways represent a challenging evolutionary puzzle that has been solved only in Drosophila melanogaster. Analyses of orthologs of the Drosophila genes identified in non-drosophilid taxa1,2  revealed that evolution of sex determination pathways is consistent with a bottom-up mode3, where only the terminal genes within the pathway are well conserved. doublesex (dsx), occupying a bottom-most position and encoding sex-specific proteins orchestrating downstream sexual differentiation processes, is an ancient sex-determining gene present in all studied species2,4,5. With the exception of lepidopterans, its female-specific splicing is known to be regulated by transformer (tra) and its co-factor transformer-2 (tra2)6-20. Here we show that in the African malaria mosquito Anopheles gambiae, a gene, which likely arose in the Anopheles lineage and which we call femaleless (fle), controls sex determination in females by regulating splicing of dsx and fruitless (fru; another terminal gene within a branch of the sex determination pathway). Moreover, fle represents a novel molecular link between the sex determination and dosage compensation pathways. It is necessary to suppress activation of dosage compensation in females, as demonstrated by the significant upregulation of the female X chromosome genes and a correlated female-specific lethality, but no negative effect on males, in response to fle knockdown. This unexpected property, combined with a high level of conservation in sequence and function in anopheline mosquitoes, makes fle an excellent target for genetic control of all major vectors of human malaria.

Kemp L, Aldridge D C, Booy O, Bower H, Browne D, Burgmann M, Burt A, Cunningham A A, Dando M, Dick J T A, Dye C, Weiss Evans S, Gallardo B, Godfray H C J, Goodfellow I, Gubbins S, Holt L A, Jones K E, Kandil H, Martin P, McCaughan M, McLeish C, Meany T, Millett K, OhEigeartaigh S S, Patron N J, Rhodes C, Roy H E, Shackelford G, Smith D, Spence N, Steiner H, Sundaram L S, Voeneky S, Walker J R, Watkins H, Whitby S, Wood J, Sutherland W J (2021)

80 questions for UK biological security

PLoS One 16 (1), e0241190

Abstract

Multiple national and international trends and drivers are radically changing what biological security means for the United Kingdom (UK). New technologies present novel opportunities and challenges, and globalisation has created new pathways and increased the speed, volume and routes by which organisms can spread. The UK Biological Security Strategy (2018) acknowledges the importance of research on biological security in the UK. Given the breadth of potential research, a targeted agenda identifying the questions most critical to effective and coordinated progress in different disciplines of biological security is required. We used expert elicitation to generate 80 policy-relevant research questions considered by participants to have the greatest impact on UK biological security. Drawing on a collaboratively-developed set of 450 questions, proposed by 41 experts from academia, industry and the UK government (consulting 168 additional experts) we subdivided the final 80 questions into six categories: bioengineering; communication and behaviour; disease threats (including pandemics); governance and policy; invasive alien species; and securing biological materials and securing against misuse. Initially, the questions were ranked through a voting process and then reduced and refined to 80 during a one-day workshop with 35 participants from a variety of disciplines. Consistently emerging themes included: the nature of current and potential biological security threats, the efficacy of existing management actions, and the most appropriate future options. The resulting questions offer a research agenda for biological security in the UK that can assist the targeting of research resources and inform the implementation of the UK Biological Security Strategy. These questions include research that could aid with the mitigation of Covid-19, and preparation for the next pandemic. We hope that our structured and rigorous approach to creating a biological security research agenda will be replicated in other countries and regions. The world, not just the UK, is in need of a thoughtful approach to directing biological security research to tackle the emerging issues.

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