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

There were a total of 2609 results for your search.
Ruckert C, Bell-Sakyi L, Fazakerley J K, Fragkoudis R (2014)

Antiviral responses of arthropod vectors: an update on recent advances

VirusDisease 25 (3), 249-260
Publisher’s version: http://dx.doi.org/10.1007/s13337-014-0217-9

Abstract

Arthropod vectors, such as mosquitoes, ticks, biting midges and sand flies, transmit many viruses that can cause outbreaks of disease in humans and animals around the world. Arthropod vector species are invading new areas due to globalisation and environmental changes, and contact between exotic animal species, humans and arthropod vectors is increasing, bringing with it the regular emergence of new arboviruses. For future strategies to control arbovirus transmission, it is important to improve our understanding of virus-vector interactions. In the last decade knowledge of arthropod antiviral immunity has increased rapidly. RNAi has been proposed as the most important antiviral response in mosquitoes and it is likely to be the most important antiviral response in all arthropods. However, other newly-discovered antiviral strategies such as melanisation and the link between RNAi and the JAK/STAT pathway via the cytokine Vago have been characterised in the last few years. This review aims to summarise the most important and most recent advances made in arthropod antiviral immunity.
Sacco M A, Nair V K (2014)

Prototype endogenous avian retroviruses of the genus Gallus

Journal of General Virology 95 (9), 2060-2070
Publisher’s version: http://dx.doi.org/10.1099/vir.0.066852-0

Abstract

Ancient endogenous retroviruses (ERVs), designated endogenous avian retrovirus (EAVs), are present in all Gallus spp. including the chicken, and resemble the modern avian sarcoma and leukosis viruses (ASLVs). The EAVs comprise several distinct retroviruses, including EAV-0, EAV-E51 and EAV-HP, as well as a putative member previously named the avian retrotransposon of chickens (ART-CH). Thus far, only the EAV-HP elements have been well characterized. Here, we determined sequences of representative EAV-0 and EAV-E51 proviruses by cloning and data mining of the 2011 assembly of the Gallus gallus genome. Although the EAV-0 elements are primarily deleted in the env region, we identified two complete EAV-0 env genes within the G. gal/us genome and prototype elements sharing identity with an EAV-E51-related clone previously designated EAV-E33. Prototype EAV-0, EAV-E51 and EAV-E33 gag, pot and env gene sequences used for phylogenetic analysis of deduced proteins showed that the EAVs formed three distinct clades, with EAV-0 sharing the last common ancestor with the ASLVs. The EAV-E51 clade showed the greatest level of divergence compared with other EAVs or ASLVs, suggesting that these ERVs represented exogenous retroviruses that evolved and integrated into the germline over a long period of time. Moreover, the degree of divergence between the chicken and red jungle fowl EAV-E51 sequences suggested that they were more ancient than the other EAVs and may have diverged through mutations that accumulated post-integration. Finally, we showed that the ART-CH elements were chimeric defective ERVs comprising portions of EAV-E51 and EAV-HP rather than authentic retrotransposons.
Sadeyen J-R, Kaiser P, Stevens M, Dziva F (2014)

Analysis of immune responses induced by avian pathogenic Escherichia coli infection in turkeys and their association with resistance to homologous re-challenge

Veterinary Research 45 (1), e19
Publisher’s version: http://dx.doi.org/10.1186/1297-9716-45-19

Abstract

Avian pathogenic Escherichia coli (APEC) cause severe respiratory and systemic disease in poultry yet the nature and consequences of host immune responses to infection are poorly understood. Here, we describe a turkey sub-acute respiratory challenge model and cytokine, cell-mediated and humoral responses associated with protection against homologous re-challenge. Intra-airsac inoculation of turkeys with 105 colony-forming units of APEC O78:H9 strain chi7122nalR induced transient and mild clinical signs of colibacillosis followed by clearance of the bacteria from the lungs and visceral organs. Upon re-challenge with 107 chi7122nalR, primed birds were solidly protected against clinical signs and exhibited negligible bacterial loads in visceral organs, whereas age-matched control birds exhibited high lesion scores and bacterial loads in the organs. Levels of mRNA for signature cytokines suggested induction of a Th1 response in the lung, whereas a distinct anti-inflammatory cytokine profile was detected in the liver. Proliferative responses of splenocytes to either Concanavalin A or soluble chi7122nalR antigens were negligible prior to clearance of bacteria, but APEC-specific responses were significantly elevated at later time intervals and at re-challenge relative to control birds. Primary infection also induced significantly elevated chi7122nalR-specific serum IgY and bile IgA responses which were bactericidal against chi7122nalR and an isogenic Deltarfb mutant. Bactericidal activity was observed in the presence of immune, but not heat-inactivated immune serum, indicating that the antibodies can fix complement and are not directed solely at the lipopolysaccharide O-antigen. Such data inform the rational design of strategies to control a recalcitrant endemic disease of poultry.
Sallu R S, Kasanga C J, Mathias M, Yongolo M, Mpelumbe-Ngeleja C, Mulumba M, Ranga E, Wambura P, Rweyemamu M, Knowles N, King D (2014)

Molecular survey for foot-and-mouth disease virus in livestock in Tanzania, 2008-2013

Onderstepoort Journal of Veterinary Research 81 (2), e736
Publisher’s version: http://dx.doi.org/10.4102/ojvr.v81i2.736

Abstract

Phylogeography data are of paramount importance in studying the molecular epidemiology dynamics of foot-and-mouth disease virus (FMDV). In this study, epithelial samples and oesophageal-pharyngeal fluids were collected from 361 convalescent animals (cattle and buffaloes) in the field throughout Tanzania between 2009 and 2013. The single plex real-time RT-PCR (qRT-PCR) assay for rapid and accurate diagnosis of FMDV employing the Callahan 3DF-2, 3DF-R primers and Callahan 3DP-1 probe were used. Preparation of the samples was performed according to the OIE manual, with a Kenya O serotype obtained from the attenuated vaccine serving as a positive control and samples collected from healthy animals serving as true negatives. The results indicated that 53.49% of samples (n = 176) were positive for FMDV genome by qRT-PCR, with Ct values ranging from 14 to 32. In addition, molecular typing of the FMDV genome positive samples using serotype specific primers revealed the existence of several serotypes: serotype South Africa Territory 1 (SAT1) (34.25%, n = 60), serotype A (68.92%, n = 98), serotype O (59.20%, n = 98) and SAT2 (54.54%, n = 96). The virus protein 1 sequences analysis for 35 samples was performed and the collective results indicated: 54.28% serotype O, 25.71% serotype A, 14.28% serotype SAT1 and 2.85% serotype SAT2. Therefore in this study, both the phylogenetic trees and spatial distribution of serotypes elucidated the phylodynamics of multiple FMDV field strains in Tanzania and neighbouring countries.
Salomonsen J, Chattaway J A, Chan A C Y, Parker A, Huguet S, Marston D A, Rogers S L, Wu Z, Smith A L, Staines K, Butter C, Riegert P, Vainio O, Nielsen L, Kaspers B, Griffin D K, Yang F, Zoorob R, Guillemot F, Auffray C, Beck S, Skjødt K, Kaufman J (2014)

Sequence of a complete chicken BG haplotype shows dynamic expansion and contraction of two gene lineages with particular expression patterns

PLoS Genetics 10 (6), e1004417
Publisher’s version: http://dx.doi.org/10.1371/journal.pgen.1004417

Abstract

Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC), and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region), and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells), correlating with two different kinds of promoters and 5? untranslated regions (5?UTR). However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.
Sanders C J, Carpenter S (2014)

Assessment of an immunomarking technique for the study of dispersal of Culicoides biting midges

Infection, Genetics and Evolution 28, 583-587
Publisher’s version: http://dx.doi.org/10.1016/j.meegid.2014.01.020

Abstract

Capture–mark–recapture techniques are used to determine the dispersal and survival of arthropods, including vector groups such as Culicoides. An assumption of these studies is that capture and the subsequent marking process does not impact of the survival and behaviour of the marked individual. The small size of Culicoides means that a significant mortality and disruption of normal behaviour such as host-location can be caused by the process of collection. Here we evaluate a technique, novel to the study of dispersal in vectors, to mark Culicoides directly and indirectly without prior capture. The acquisition and subsequent detection of marker protein by Culicoides exposed to a treated substrate was investigated in the laboratory. The technique was then assessed in a small-scale field trial where a defined section of resting habitat was sprayed with an egg white solution and Culicoides caught within the vicinity were tested for the presence of egg protein. It was found that up to 100% of Culicoides acquired the protein marker in the laboratory with no apparent impact on survival. In the field, pools of Culicoides obsoletus collected next to the treated area were found to be positive for the protein, suggesting that the technique could be used in larger-scale studies. The definition of a behaviourally non-invasive technique for marking Culicoides will greatly increase our understanding of the natural dispersal behaviour of Culicoides and other vectors
Sanderson N D, Norman P J, Guethlein L A, Ellis S A, Williams C, Breen M, Park S D E, Magee D A, Babrzadeh F, Warry A, Watson M, Bradley D G, MacHugh D E, Parham P, Hammond J A (2014)

Definition of the cattle killer cell Ig–like receptor gene family: comparison with aurochs and human counterparts

Journal of Immunology 193 (12), 6016-6030
Publisher’s version: http://dx.doi.org/10.4049/jimmunol.1401980

Abstract

Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig–like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle.
Schnettler E, Tykalova H, Watson M, Sharma M, Sterken M G, Obbard D J, Lewis S H, McFarlane M, Bell-Sakyi L, Barry G, Weisheit S, Best S M, Kuhn R J, Pijlman G P, Chase-Topping M E, Gould E A, Grubhoffer L, Fazakerley J K, Kohl A (2014)

Induction and suppression of tick cell antiviral RNAi responses by tick-borne flaviviruses

Nucleic Acids Research 42 (14), 9436-9446
Publisher’s version: http://dx.doi.org/10.1093/nar/gku657

Abstract

Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class Insecta) and ticks (class Arachnida). RNA interference (RNAi) is the major antiviral mechanism in arthropods against arboviruses. Unlike in mosquitoes, tick antiviral RNAi is not understood, although this information is important to compare arbovirus/host interactions in different classes of arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute proteins involved in RNAi and the response against tick-borne Langat virus (Flaviviridae) replication were identified and phylogenetic relationships characterized. Analysis of small RNAs in infected cells showed the production of virus-derived small interfering RNAs (viRNAs), which are key molecules of the antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than those from other arbovirus vectors and mapped at highest frequency to the termini of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick-borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick RNAi. Our results characterize the antiviral RNAi response in tick cells including phylogenetic analysis of genes encoding antiviral proteins, and viral interference with this pathway. This shows important differences in antiviral RNAi between the two major classes of arbovirus vectors, and our data broadens our understanding of arthropod antiviral RNAi.
Schwartz J C, Murtaugh M P (2014)

Characterization of a polymorphic IGLV gene in pigs (Sus scrofa)

Immunogenetics 66 (7-8), 507-511
Publisher’s version: http://dx.doi.org/10.1007/s00251-014-0785-2

Abstract

Swine, unlike other artiodactyls, but similar to humans, utilize both lambda and kappa light chain isotypes almost equally in the generation of their antibody repertoire. The porcine antibody light chain loci have previously been characterized in a single Duroc sow in which was seen extensive allelic variation between light chain genes on homologous chromosomes. However, the extent of variation between individuals is completely unknown. Using deep sequencing of cDNA-derived amplicons from five pigs, we report the identification and characterization of an IGLV gene that is functional and highly expressed in some animals, yet completely absent in others. Our findings provide a possible rationale for the known individual-to-individual variation in antibody responses to vaccination, infectious challenge, and subsequent disease outcome.
Searle K R, Barber J, Stubbins F, Labuschagne K, Carpenter S, Butler A, Denison E, Sanders C, Mellor P S, Wilson A, Nelson N, Gubbins S, Purse B V (2014)

Environmental drivers of Culicoides phenology: How important is species-specific variation when determining disease policy?

PLoS ONE 9 (11), e111876
Publisher’s version: http://dx.doi.org/10.1371/journal.pone.0111876

Abstract

Since 2006, arboviruses transmitted by Culicoides biting midges (Diptera: Ceratopogonidae) have caused significant disruption to ruminant production in northern Europe. The most serious incursions involved strains of bluetongue virus (BTV), which cause bluetongue (BT) disease. To control spread of BTV, movement of susceptible livestock is restricted with economic and animal welfare impacts. The timing of BTV transmission in temperate regions is partly determined by the seasonal presence of adult Culicoides females. Legislative measures therefore allow for the relaxation of ruminant movement restrictions during winter, when nightly light-suction trap catches of Culicoides fall below a threshold (the ‘seasonally vector free period’: SVFP). We analysed five years of time-series surveillance data from light-suction trapping in the UK to investigate whether significant inter-specific and yearly variation in adult phenology exists, and whether the SVFP is predictable from environmental factors. Because female vector Culicoides are not easily morphologically separated, inter-specific comparisons in phenology were drawn from male populations. We demonstrate significant inter-specific differences in Culicoides adult phenology with the season of Culicoides scoticus approximately eight weeks shorter than Culicoides obsoletus. Species-specific differences in the length of the SVFP were related to host density and local variation in landscape habitat. When the Avaritia Culicoides females were modelled as a group (as utilised in the SFVP), we were unable to detect links between environmental drivers and phenological metrics. We conclude that the current treatment of Avaritia Culicoides as a single group inhibits understanding of environmentally-driven spatial variation in species phenology and hinders the development of models for predicting the SVFP from environmental factors. Culicoides surveillance methods should be adapted to focus on concentrated assessments of species-specific abundance during the start and end of seasonal activity in temperate regions to facilitate refinement of ruminant movement restrictions thereby reducing the impact of Culicoides-borne arboviruses.

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