Publications

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

There were a total of 2603 results for your search.
Cabezas-Cruz A, Passos L M F, Lis K, Kenneil R, Valdes J J, Ferrolho J, Tonk M, Pohl A E, Grubhoffer L, Zweygarth E, Shkap V, Ribeiro M F B, Estrada-Pena A, Kocan K M, de la Fuente J (2013)

Functional and immunological relevance of Anaplasma marginale major surface protein 1a sequence and structural analysis

PLoS ONE 8 (6), e65243

Abstract

Bovine anaplasmosis is caused by cattle infection with the tick-borne bacterium, Anaplasma marginale. The major surface protein 1a (MSP1a) has been used as a genetic marker for identifying A. marginale strains based on N-terminal tandem repeats and a 5'-UTR microsatellite located in the msp1a gene. The MSP1a tandem repeats contain immune relevant elements and functional domains that bind to bovine erythrocytes and tick cells, thus providing information about the evolution of host-pathogen and vector-pathogen interactions. Here we propose one nomenclature for A. marginale strain classification based on MSP1a. All tandem repeats among A. marginale strains were classified and the amino acid variability/frequency in each position was determined. The sequence variation at immunodominant B cell epitopes was determined and the secondary (2D) structure of the tandem repeats was modeled. A total of 224 different strains of A. marginale were classified, showing 11 genotypes based on the 5'-UTR microsatellite and 193 different tandem repeats with high amino acid variability per position. Our results showed phylogenetic correlation between MSP1a sequence, secondary structure, B-cell epitope composition and tick transmissibility of A. marginale strains. The analysis of MSP1a sequences provides relevant information about the biology of A. marginale to design vaccines with a cross-protective capacity based on MSP1a B-cell epitopes.
Carpenter S, Groschup M H, Garros C, Felippe-Bauer M L, Purse B V (2013)

Culicoides biting midges, arboviruses and public health in Europe

Antiviral Research 100 (1), 102-113

Abstract

The emergence of multiple strains of bluetongue virus (BM and the recent discovery of Schmallenberg virus (SBV) in Europe have highlighted the fact that exotic Culicoides-borne arboviruses from remote geographic areas can enter and spread rapidly in this region. This review considers the potential for this phenomenon to impact on human health in Europe, by examining evidence of the role of Culicoides biting midges in the zoonotic transmission and person-to-person spread of arboviruses worldwide. To date, the only arbovirus identified as being primarily transmitted by Culicoides to and between humans is Oropouche virus (OROV). This member of the genus Orthobunyavirus causes major epidemics of febrile illness in human populations of South and Central America and the Caribbean. We examine factors promoting sustained outbreaks of OROV in Brazil from an entomological perspective and assess aspects of the epidemiology of this arbovirus that are currently poorly understood, but may influence the risk of incursion into Europe. We then review the secondary and rarely reported role of Culicoides in the transmission of high-profile zoonotic infections, while critically reviewing evidence of this phenomenon in endemic transmission and place this in context with the presence of other potential vector groups in Europe. Scenarios for the incursions of Culicoides-borne human-to-human transmitted and zoonotic arboviruses are then discussed, along with control measures that could be employed to reduce their impact. These measures are placed in the context of legislative measures used during current and ongoing outbreaks of Culicoides-borne arboviruses in Europe, involving both veterinary and public health sectors.
Carr B V, Lefevre E A, Windsor M A, Inghese C, Gubbins S, Prentice H, Juleff N D, Charleston B (2013)

CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle

Journal of General Virology 94 (1), 97-107

Abstract

We have performed a series of studies to investigate the role of CD4+ T-cells in the immune response to foot-and-mouth disease virus (FMDV) post-vaccination. Virus neutralizing antibody titres (VNT) in cattle vaccinated with killed FMD commercial vaccine were significantly reduced and class switching delayed as a consequence of rigorous in vivo CD4+ T-cell depletion. Further studies were performed to examine whether the magnitude of T-cell proliferative responses correlated with the antibody responses. FMD vaccination was found to induce T-cell proliferative responses, with CD4+ T-cells responding specifically to the FMDV antigen. In addition, gamma interferon (IFN-?) was detected in the supernatant of FMDV antigen-stimulated PBMC and purified CD4+ T-cells from vaccinated cattle. Similarly, intracellular IFN-? could be detected specifically in purified CD4+ T-cells after restimulation. It was not possible to correlate in vitro proliferative responses or IFN-? production of PBMC with VNT, probably as a consequence of the induction of T-independent and T-dependent antibody responses and antigen non-specific T-cell responses. However, our studies demonstrate the importance of stimulating CD4+ T-cell responses for the induction of optimum antibody responses to FMD-killed vaccines.

Abstract

Bovine viral diarrhoea virus (BVDV) causes widespread infection of cattle populations worldwide and, even though the majority of infections go unnoticed, is an important disease. BVDV infection impacts on animal welfare and causes significant economic losses. Approximately 1 per cent of cattle are persistently infected with BVDV and are the major source of infection within a herd. Persistently infected cattle can be clinically normal yet shed high titres of infectious virus. BVDV naive animals may succumb to acute infection, usually due to contact with a persistently infected animal. By contrast, the spread of the virus by animals with acute infection may be quite inefficient. The lesson from countries such as Norway is that eradication can be achieved. Complex logistical issues must be resolved in order to mount a successful national eradication campaign, and coordination of resources is a major challenge, but, as other countries have shown, we have sufficient knowledge of this virus to eliminate the sources of infection.
Chase-Topping M E, Handel I, Bankowski B M, Juleff N D, Gibson D, Cox S J, Windsor M A, Reid E, Doel C, Howey R, Barnett P V, Woolhouse M E J, Charleston B (2013)

Understanding foot-and-mouth disease virus transmission biology: identification of the indicators of infectiousness

Veterinary Research 44, e46

Abstract

The control of foot-and-mouth disease virus (FMDV) outbreaks in non-endemic countries relies on the rapid detection and removal of infected animals. In this paper we use the observed relationship between the onset of clinical signs and direct contact transmission of FMDV to identify predictors for the onset of clinical signs and identify possible approaches to preclinical screening in the field. Threshold levels for various virological and immunological variables were determined using Receiver Operating Characteristic (ROC) curve analysis and then tested using generalized linear mixed models to determine their ability to predict the onset of clinical signs. In addition, concordance statistics between qualitative real time PCR test results and virus isolation results were evaluated. For the majority of animals (71%), the onset of clinical signs occurred 3-4 days post infection. The onset of clinical signs was associated with high levels of virus in the blood, oropharyngeal fluid and nasal fluid. Virus is first detectable in the oropharyngeal fluid, but detection of virus in the blood and nasal fluid may also be good candidates for preclinical indicators. Detection of virus in the air was also significantly associated with transmission. This study is the first to identify statistically significant indicators of infectiousness for FMDV at defined time periods during disease progression in a natural host species. Identifying factors associated with infectiousness will advance our understanding of transmission mechanisms and refine intra-herd and inter-herd disease transmission models.

Chaudhuri R R, Morgan E, Peters S E, Pleasance S J, Hudson D L, Davies H M, Wang J, van Diemen P M, Buckley A M, Bowen A J, Pullinger G D, Turner D J, Langridge G C, Turner A K, Parkhill J, Charles I G, Maskell D J, Stevens M P (2013)

Comprehensive assignment of roles for salmonella typhimurium genes in intestinal colonization of food-producing animals

PLoS Genetics 9 (4), e1003456

Abstract

Salmonella Typhimurium is a major cause of human diarrhoeal infections, usually acquired from chickens, pigs, cattle, or their products. To understand the basis of persistence and pathogenesis in these reservoir hosts, and to inform the design of novel vaccines and treatments, we generated a library of 7,702 S. Typhimurium mutants, each bearing an insertion at a random position in the genome. Using DNA sequencing, we identified the disrupted gene in each mutant and determined its relative abundance in a laboratory culture and after experimental infection of mice, chickens, pigs, and cattle. The method allowed large numbers of mutants to be investigated simultaneously, drastically reducing the number of animals required to perform a comprehensive screen. We identified mutants that grow in culture but do not survive in one or more of the animals. The genes disrupted in these mutants are inferred to be important for the infection process. Most of these genes were required in all three food-producing animals, but smaller subsets of genes may mediate persistence in a specific host species. The data provide the most comprehensive map of virulence-associated genes for any bacterial pathogen in natural hosts and are highly relevant for the design of control strategies.

Abstract

Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV) and measles virus (MeV) have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFN?/?) and type II (IFN?) interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV), measles virus (MeV), peste des petits ruminants virus (PPRV) and canine distemper virus (CDV). These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action

Abstract

Vaccination is considered one of the most effective ways to control pathogens and prevent diseases in humans as well as in the veterinary field. Traditional vaccines against animal viral diseases are based on inactivated or attenuated viruses, but new subunit vaccines are gaining attention from researchers in animal vaccinology. Among these, virus-like particles (VLPs) represent one of the most appealing approaches opening up interesting frontiers in animal vaccines. VLPs are robust protein scaffolds exhibiting well-defined geometry and uniformity 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; nevertheless, only one veterinary VLP-base vaccine is licensed. Here, we review and examine in detail the current status of VLPs as a vaccine strategy in the veterinary field, and discuss the potential advantages and challenges of this technology.
Crisci E, Mussa T, Fraile L, Montoya M (2013)

Review: Influenza virus in pigs

Molecular Immunology 55 (3-4), 200-211

Abstract

Influenza virus disease still remains one of the major threats to human health, involving a wide range of animal species and pigs play an important role in influenza ecology. Pigs were labeled as "mixing vessels" since they are susceptible to infection with avian, human and swine influenza viruses and genetic reassortment between these viruses can occur. After the H1N1 influenza pandemic of 2009 with a swine origin virus, the most recent research in "influenzology" is directed at improving knowledge of porcine influenza virus infection. This tendency is probably due to the fact that domestic pigs are closely related to humans and represent an excellent animal model to study various microbial infectious diseases. In spite of the role of the pig in influenza virus ecology, swine immune responses against influenza viruses are not fully understood. Considering these premises, the aim of this review is to focus on the in vitro studies performed with porcine cells and influenza virus and on the immune responses of pigs against human, avian and swine influenza viruses in vivo. The increased acceptance of pigs as suitable and valuable models in the scientific community may stimulate the development of new tools to assess porcine immune responses, paving the way for their consideration as the future "gold standard" large-animal model in immunology.
Crooijmans R P M A, Fife M S, Fitzgerald T W, Strickland S, Cheng H H, Kaiser P, Redon R, Groenen M A M (2013)

Large scale variation in DNA copy number in chicken breeds

BMC Genomics 14, e398

Abstract

Detecting genetic variation is a critical step in elucidating the molecular mechanisms underlying phenotypic diversity. Until recently, such detection has mostly focused on single nucleotide polymorphisms (SNPs) because of the ease in screening complete genomes. Another type of variant, copy number variation (CNV), is emerging as a significant contributor to phenotypic variation in many species. Here we describe a genome-wide CNV study using array comparative genomic hybridization (aCGH) in a wide variety of chicken breeds. We identified 3,154 CNVs, grouped into 1,556 CNV regions (CNVRs). Thirty percent of the CNVs were detected in at least 2 individuals. The average size of the CNVs detected was 46.3 kb with the largest CNV, located on GGAZ, being 4.3 Mb. Approximately 75% of the CNVs are copy number losses relatively to the Red Jungle Fowl reference genome. The genome coverage of CNVRs in this study is 60 Mb, which represents almost 5.4% of the chicken genome. In particular large gene families such as the keratin gene family and the MHC show extensive CNV.

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