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

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Djebali S, Davis C A, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov G K, Khatun J, Williams B A, Zaleski C, Rozowsky J, Roeder M, Kokocinski F, Abdelhamid R F, Alioto T, Antoshechkin I, Baer M T, Bar N S, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood M J, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo O J, Park E, Persaud K, Preall J B, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See L-H, Shahab A, Skancke J, Suzuki A M, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis S E, Hannon G, Giddings M C, Ruan Y, Wold B, Carninci P, Guigo R, Gingeras T R (2012)

Landscape of transcription in human cells

Nature 489 (7414), 101-108


Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.


The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696).
El Harrak M, Touil N, Loutfi C, Hammouchi M, Parida S, Sebbar G, Chaffai N, Harif B, Messoudi N, Batten C, Oura C A L (2012)

A reliable and reproducible experimental challenge model for peste des petits ruminants virus

Journal of Clinical Microbiology 50 (11), 3738-3740


Experimental challenge protocols that consistently reproduce clinical signs of peste des petits ruminants in Alpine goats infected with a tissue culture-passaged peste des petits ruminants virus are described. The protocols can be used to carry out quality-controlled vaccine efficacy and pathogenesis studies under experimental conditions.


Major histocompatibility complex (MHC) genes play a key role in immunity to infectious pathogens. Their high level of diversity is a functionally important characteristic. In cattle our knowledge of MHC diversity and the functional distinction between genes is limited. Recent studies in commercially important dairy cattle populations reveal that MHC class I diversity is relatively low, although it does not appear to be declining. The presence and frequency of some genes and alleles was markedly different between geographically distinct populations, and trait selection was implicated as an influential force. Functional studies suggest that some alleles may have a disproportionally high impact on T cell responses, thus it may be important to consider their role in both disease resistance and vaccine efficacy. It is clear that increasing our knowledge of the functional capabilities of different cattle MHC class I genes is essential to maintain healthy populations in the future.


Epizootic hemorrhagic disease virus (EHDV), an arthropod-borne orbivirus (family Reoviridae), is an emerging pathogen of wild and domestic ruminants that is closely related to bluetongue virus (BTV). The present study examines the outcome of an experimental EHDV-7 infection of Holstein cattle and East Frisian sheep. Apart from na ve animals that had not been exposed to BTV, it included animals that had been experimentally infected with either BTV-6 or BTV-8 two months earlier. In addition, EHDV-infected cattle were subsequently challenged with BTV-8. Samples were tested with commercially available ELISA and real-time RT-PCR kits and a custom NS3-specific real-time RT-PCR assay. Virus isolation was attempted in Vero, C6/36 and KC cells (from Culicoides variipennis), embryonated chicken eggs and type I interferon receptor-deficient IFNAR-I- mice. EHDV-7 productively infected Holstein cattle, but caused no clinical signs. The inoculation of East Frisian sheep, on the other hand, apparently did not lead to a productive infection. The commercial diagnostic kits performed adequately. KC cells proved to be the most sensitive means of virus isolation, but viremia was shorter than 2 weeks in most animals. No interference between EHDV and BTV infection was observed; therefore the pre-existing immunity to some BTV serotypes in Europe is not expected to protect against a possible introduction of EHDV, in spite of the close relation between the viruses.


Two lateral flow devices (LFD) for the detection of vesicular stomatitis (VS) virus (VSV), types Indiana (VSV-IND) and New Jersey (VSV-NJ) were developed using monoclonal antibodies Cl and F25VSVNJ-45 to the respective VSV serotypes. The performance of the LFDs was evaluated in the laboratory on suspensions of vesicular epithelia and cell culture passage derived supernatants of VSV. The collection of test samples included 105 positive for VSV-IND (92 vesicular epithelial suspensions and 13 cell culture antigens; encompassing 93 samples of subtype 1 [VSV-IND-1],9 of subtype 2 [VSV-IND-2] and 3 of subtype 3 [VSV-IND-3]) and 189 positive for VSV-NJ (162 vesicular epithelial suspensions and 27 cell culture antigens) from suspected cases of vesicular disease in cattle and horses collected from 11 countries between 1937 and 2008 or else were derived from experimental infection and 777 samples that were either shown to be positive or negative for foot-and-mouth disease (FMD) virus (FMDV) and swine vesicular disease virus (SVDV) or else collected from healthy cattle or pigs and collected from 68 countries between 1965 and 2011. The diagnostic sensitivity of the VSV-IND (for reaction with VSV-IND-1) and VSV-NJ LFDs was either similar or identical at 94.6% (VSV-IND) and 97.4% (VSV-NJ) compared to 92.5% and 97.4% obtained by the reference method of antigen ELISA. The VSV-IND LFD failed to react with viruses of VSV-IND-2 and 3, while the VSV-NJ device recognized all VSV-NJ virus strains. The diagnostic specificities of the VSV-IND and VSV-NJ LFDs were 99.1% and 100, respectively, compared to 99.6% and 99.8% for the ELISA. Reactions with FMDV which can produce indistinguishable syndromes clinically in cattle, pigs and sheep and SVDV (vesicular disease in pigs) did not occur. These data illustrate the potential for the LFDs to be used next to the animal for providing rapid and objective support to veterinarians in their clinical judgment of vesicular disease and for the subtype (VSV-IND-1) and type-specific (VSV-NJ) pen-side diagnosis of VS and differential diagnosis from FMD.
Foley-Fisher M, Phipps P, Medlock J M, Atkinson P, Atkinson B, Hewson R, Gale P (2012)

Ticks on northward migrating birds in southern Spain during Spring, 2011

Journal of Vector Ecology 37 (2), 478-480


This study describes a comparison of the efficacy of the Monty Roberts horsemanship technique (MRT) in comparison with a UK conventional training technique (CT) for the initial training of horses. The sample consisted of 14 untrained horses, between 3 and 5 years old, sourced from a variety of non-competition yards in the UK. Horses were matched on temperament and randomly assigned to either the MRT group or the CT group. Each trainer was allowed 30 minutes per day to work with each horse for 20 days, following which the horses undertook a standardized ridden obstacle and flatwork test and a ridden freestyle test. Horses were scored for technical performance by a panel of judges who were unaware of the study or the trainers involved. During the session where the first saddle and rider were achieved, MRT-trained horses had significantly lower (p = 0.0137) maximum heart rates (bpm ± SD) (first saddle: 127 ± 37, first rider: 76 ± 12) when compared with CT-trained horses (first saddle: 176 ± 24, first rider: 147 ± 61). MRT-trained horses had similar mean heart rates to CT-trained horses (91 ± 15 bpm, 80 ± 7 bpm, respectively) during the ridden obstacle test but received significantly higher performance scores from the judges (171 ± 4, 133 ± 7, respectively; p


Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae, contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G-interacting domain is structurally distinct, although it contains an apical eIF4G-interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract-binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin.

Dietrich I, Hosie M J, Willett B J (2011)

The role of BST2/tetherin in feline retrovirus infection

Veterinary Immunology and Immunopathology 143 (03-Apr), 255-64


Pathogenic retroviral infections of mammals have induced the evolution of cellular anti-viral restriction factors and have shaped their biological activities. This intrinsic immunity plays an important role in controlling viral replication and imposes a barrier to viral cross-species transmission. Well-studied examples of such host restriction factors are TRIM5alpha, an E3 ubiquitin ligase that binds incoming retroviral capsids in the cytoplasm via its C-terminal PRY/SPRY (B30.2) domain and targets them for proteasomal degradation, and APOBEC3 proteins, cytidine deaminases that induce hypermutation and impair viral reverse transcription. Tetherin (BST-2, CD317) is an interferon-inducible transmembrane protein that potently inhibits the release of nascent retrovirus particles in single-cycle replication assays. However, whether the primary biological activity of tetherin in vivo is that of a restriction factor remains uncertain as recent studies on human tetherin suggest that it is unable to prevent spreading infection of human immunodeficiency virus type 1 (HIV-1). The feline tetherin homologue resembles human tetherin in amino acid sequence, protein topology and anti-viral activity. Transiently expressed feline tetherin displays potent inhibition of feline immunodeficiency virus (FIV) and HIV-1 particle release. However, stable ectopic expression of feline tetherin in a range of feline cell lines has no inhibitory effect on the growth of either primary or cell culture-adapted strains of FIV. By comparing and contrasting the activities of the felid and primate tetherins against their respective immunodeficiency-causing lentiviruses we may gain insight into the contribution of tetherins to the control of lentiviral replication and the evolution of lentiviral virulence.


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