Publications

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

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Abstract

The major histocompatibility complex (MHC) is one of the most diverse regions of the mammalian genome. Diversity in MHC genes is integral to their function in the immune system, and while pathogens play a key role in shaping this diversity, the contribution of other selective forces remains unclear. The controlled breeding of cattle offers an excellent model for the identification and exploration of these forces. We characterized the MHC class I genes present in a sample of Canadian Holstein A.I. bulls and compared the results with those obtained in an earlier study. No evidence for a reduction in MHC diversity over 20 years was observed, but the relative frequency of some haplotypes had changed: the formerly rare A12 (w12B) haplotype had become the most common, together with A15, while A19, which dominated the earlier sample, had significantly reduced in frequency. Only 7% of bulls in the current study were MHC homozygous compared with the 14% expected under HardyWeinberg. To identify the selective forces at work, a gene substitution model was used to calculate the effects of MHC on selection traits using estimated breeding values for each bull. Significant associations between MHC and production, disease and fertility traits were identified, suggesting that MHC diversity is not merely shaped by disease in this controlled breeding system. The decrease in a common haplotype, the reduced number of homozygous bulls and the associations with disease and production traits together indicate that MHC diversity in dairy cattle is maintained by heterozygote advantage.

Abstract

Tomato (Solanum lycopersicum) is a major crop plant and a model system for fruit development. Solanum is one of the largest angiosperm genera(1) and includes annual and perennial plants from diverse habitats. Here we present a high-quality genome sequence of domesticated tomato, a draft sequence of its closest wild relative, Solanum pimpinellifolium(2), and compare them to each other and to the potato genome (Solanum tuberosum). The two tomato genomes show only 0.6% nucleotide divergence and signs of recent admixture, but show more than 8% divergence from potato, with nine large and several smaller inversions. In contrast to Arabidopsis, but similar to soybean, tomato and potato small RNAs map predominantly to gene-rich chromosomal regions, including gene promoters. The Solanum lineage has experienced two consecutive genome triplications: one that is ancient and shared with rosids, and a more recent one. These triplications set the stage for the neofunctionalization of genes controlling fruit characteristics, such as colour and fleshiness.

Abstract

Vaccination continues to be the main approach to protect animals from infectious diseases. Until recently, all licensed vaccines were developed using conventional technologies. Subunit vaccines are, however, gaining attention from researchers in the field of veterinary vaccinology, and among these, virus-like particles (VLPs) represent one of the most appealing approaches. VLPs are robust protein cages in the nanometer range that mimic the overall structure of the native virions but lack the viral genome. They are often antigenically indistinguishable from the virus from which they were derived and present important advantages in terms of safety. VLPs can stimulate strong humoral and cellular immune responses and have been shown to exhibit self-adjuvanting abilities. In addition to their suitability as a vaccine for the homologous virus from which they are derived, VLPs can also be used as vectors for the multimeric presentation of foreign antigens. VLPs have therefore shown dramatic effectiveness as candidate vaccines. Here, we review the current status of VLPs as a vaccine technology in the veterinary field, and discuss the potential advantages and challenges of this technology.
Crisci E, Fraile L, Moreno N, Blanco E, Cabezon R, Costa C, Mussa T, Baratelli M, Martinez-Orellana P, Ganges L, Martinez J, Barcena J, Montoya M (2012)

Chimeric calicivirus-like particles elicit specific immune responses in pigs

Vaccine 30 (14), 2427-2439

Abstract

Virus-like particles (VLPs) have received considerable attention due to their potential application in veterinary vaccines and, in particular, VLPs from rabbit haemorrhagic disease virus (RHDV) have successfully shown to be good platforms for inducing immune responses against an inserted foreign epitope in mice. The aim of this study was to assess the immunogenicity of chimeric RHDV-VLPs as vaccine vectors in pigs. For this purpose, we have generated chimeric VLPs containing a well-known T epitope of 3A protein of foot-and-mouth disease virus (FMDV). Firstly, RHDV-VLPs were able to activate immature porcine bone marrow-derived dendritic cells (poBMDCs) in vitro. Secondly, pigs were inoculated twice in a two-week interval with chimeric RHDV-VLPs at different doses intranasally or intramuscularly. One intramuscularly treated group was also inoculated with adjuvant Montanide (TM) ISA 206 at the same time. Specific IgG and IgA antibodies against RHDV-VLPs were induced and such levels were higher in the adjuvanted group compared with other groups. Interestingly, anti-RHDV-VLP IgA responses were higher in groups inoculated intramuscularly than those that received the VLPs intranasally. Two weeks after the last immunisation, specific IFN-gamma-secreting cells against 3A epitope and against RHDV-VLPs were detected in PBMCs by ELISPOT. The adjuvanted group exhibited the highest IFN-gamma-secreting cell numbers and lymphoproliferative specific T cell responses against 3A epitope and RHDV-VLP. This is the first immunological report on the potential use of chimeric RHDV-VLPs as antigen carriers in pigs.
Darpel K E, Monaghan P, Simpson J, Anthony S J, Veronesi E, Brooks H W, Elliott H, Brownlie J, Takamatsu H H, Mellor P S, Mertens P P C (2012)

Involvement of the skin during bluetongue virus infection and replication in the ruminant host

Veterinary Research 43, 40

Abstract

Bluetongue virus (BTV) is a double stranded (ds) RNA virus (genus Orbivirus; family Reoviridae), which is considered capable of infecting all species of domestic and wild ruminants, although clinical signs are seen mostly in sheep. BTV is arthropod-borne ("arbovirus") and able to productively infect and replicate in many different cell types of both insects and mammalian hosts. Although the organ and cellular tropism of BTV in ruminants has been the subject of several studies, many aspects of its pathogenesis are still poorly understood, partly because of inherent problems in distinguishing between "virus replication" and "virus presence". BTV replication and organ tropism were studied in a wide range of infected sheep tissues, by immuno-fluorescence-labeling of non-structural or structural proteins (NS2 or VP7 and core proteins, respectively) using confocal microscopy to distinguish between virus presence and replication. These results are compared to gross and microscopic pathological findings in selected organs from infected sheep. Replication was demonstrated in two major cell types: vascular endothelial cells, and agranular leukocytes which morphologically resemble lymphocytes, monocytes/macrophages and/or dendritic cells. Two organs (the skin and tonsils) were shown to support relatively high levels of BTV replication, although they have not previously been proposed as important replication sites during BTV infection. The high level of BTV replication in the skin is thought to be of major significance for the pathogenesis and transmission of BTV (via biting insects) and a refinement of our current model of BTV pathogenesis is discussed.

Abstract

Following reports of increased mortality in the small ruminant population of the Sahrawi territories, western Algeria, between January and May 2010, local veterinary authorities suspected an outbreak of peste des petits ruminants (PPR). An investigation was implemented in May 2010 and followed up in October 2010 in the Sahrawi refugee camps, Tindouf province, with the objective of confirming the circulation of the peste des petits ruminants virus (PPRV). Laboratory results confirmed the presence of PPRV in 33.3% of the samples. Sequence analysis revealed that the virus belonged to Lineage IV and phylogenetic analysis indicated a close relationship (99.3%) with the PPRV isolated during the Moroccan outbreak in 2008.
Deuchande R, Murphy A, Otter A, Baigent S, Wood A, Irvine R M (2012)

Marek's disease in turkeys (letter)

Veterinary Record 171 (23), 602
Publisher’s version: http://dx.doi.org/10.1136/vr.e8274

Abstract

The protective immune response generated by a commercial monovalent inactivated vaccine against bluetongue virus serotype 1 (BTV1) was studied. Five sheep were vaccinated, boost-vaccinated, and then challenged against BTV1 ALG/2006. RT-PCR did not detect viremia at any time during the experiment. Except a temperature increase observed after the initial and boost vaccinations, no clinical signs or lesions were observed. A specific and protective antibody response checked by ELISA was induced after vaccination and boost vaccination. This specific antibody response was associated with a significant increase in B lymphocytes confirmed by flow cytometry, while significant increases were not observed in T lymphocyte subpopulations (CD4 +, CD8 +, and WC1 +), CD25 + regulatory cells, or CD14 + monocytes. After challenge with BTV1, the antibody response was much higher than during the boost vaccination period, and it was associated with a significant increase in B lymphocytes, CD14 + monocytes, CD25 + regulatory cells, and CD8 + cytotoxic T lymphocytes.
Dixon L K, Takamatsu H (2012)

African swine fever virus: current situation and prospects for control

Pig Journal 67, 11-17
Publisher’s version:

Abstract

African swine fever virus (ASFV) causes a haemorrhagic fever in domestic pigs which results in high mortality and has a severe socio-economic impact in affected countries. The disease is endemic in many sub-Saharan countries in Africa and the virus is maintained in an ancient sylvatic cycle in Eastern and Southern Africa. The few trans-continental transmissions of ASFV that have occurred have proven difficult and costly to eradicate. Following the introduction of ASFV into Georgia in the Trans-Caucasus region in 2007, the disease spread to neighbouring countries including the Russian Federation. The risk of further global spread has increased and threatens pig farming worldwide. The stability of the virus in meat products, the presence of wildlife reservoirs and the lack of a vaccine contribute to difficulties in control.

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