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

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Shini S, Huff G R, Shini A, Kaiser P (2010)

Understanding stress-induced immunosuppression: Exploration of cytokine and chemokine gene profiles in chicken peripheral leukocytes

Poultry Science 89 (4), 841-851
Publisher’s version: http://dx.doi.org/10.3382/ps.2009-00483

Abstract

At present, the poultry meat and egg industry has gained a lot of ground, being viewed as a provider of a healthy alternative to red meat and other protein sources. If this trend is to be maintained, solutions must be found to improve resistance of chickens to disease, which often is weakened by stressful conditions. In poultry, stress-induced immunosuppression is manifested by failures in vaccination and increased morbidity and mortality of flocks. Currently, several modern cellular and molecular approaches are being used to explore the status of the immune system during stress and disease. It is likely that these new techniques will lead to the development of new strategies for preventing and controlling immunosuppression in poultry. Using quantitative reverse transcription-PCR assays, a broad spectrum of cytokine, chemokine, and their receptor genes can be quantified in birds and then be used as markers to assess the effects of stress on the immune system. Currently, we are investigating immune and endocrine interactions in the chicken, in particular the cells and molecules that are known to be involved in such interactions in mammals. We have evaluated the effects of corticosterone administration in drinking water on peripheral lymphocyte and heterophil cytokine and chemokine gene profiles. In particular, there seems to be effects on cytokine and chemokine mRNA expression levels in both lymphocytes and heterophils, especially expression of the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and IL-18 and chemokines C-C motif, ligand 1 inflammatory (CCLi1); C-C motif, ligand 2 inflammatory (CCLi2); C-C motif, ligand 5 (CCL5); C-C motif, ligand 16 (CCL16); C-X-C motif ligand 1 inflammatory (CXCLi1); and C-X-C motif ligand 2 inflammatory (CXCLi2), which are initially upregulated and are potentially involved in modulating the adaptive immune response. A chronic treatment with corticosterone downregulates proinflammatory cytokines and chemokines, suggesting that the delayed effects of chronic stress can suppress the immune response. Messenger RNA expression levels of transforming growth factor-beta 4 (TGF-beta 4) are also upregulated in cortisosterone-treated birds. It appears that the balance between T-helper (Th) 1 and Th2/T regulatory cytokine production is altered in conditions associated with significant changes in plasma corticosterone concentration. Experiments are underway to decipher the cytokine and chemokine responses to vaccination and bacterial challenge on the background of stress-induced immunosuppression.
Shini S, Shini A, Kaiser P (2010)

Cytokine and chemokine gene expression profiles in heterophils from chickens treated with corticosterone

Stress 13 (3), 185-194
Publisher’s version: http://dx.doi.org/10.3109/10253890903144639

Abstract

In chickens, corticosterone is the end-product of stress. However, the nature of the immune response to elevated plasma corticosterone concentrations at the molecular level has not yet been characterised. We recently demonstrated that exposure to corticosterone in drinking water for 1 week significantly upregulates mRNA expression levels for the pro-inflammatory interleukins (IL)-1 beta, IL-6, IL-18 and the pro-inflammatory chemokine CCLi2 in chicken lymphocytes, particularly 3 h after the treatment started. In the present study, we investigated cytokine and chemokine mRNA expression levels in circulating heterophils of chickens, and show that at 3 h post initial treatment with corticosterone in drinking water (20 mg/1L) the mRNA expression levels for IL-1 beta, IL-6, IL-10, IL-12 alpha and IL-18 are upregulated. The mRNA expression levels for IL-6, IL-10 and IL-18 correlate with plasma corticosterone concentration and total heterophil counts. Corticosterone downregulated the expression levels of all pro-inflammatory cytokines at 24 h and 1 week post-treatments. Repeated treatment with corticosterone upregulated mRNA expression levels of transforming growth factor-beta 4 and the chemokine CCL16. These data indicate that cytokine and chemokine gene expression signatures in chicken heterophils can be altered during stress and therefore could be used as an indicator of stress
Silva-Campa E, Cordoba L, Fraile L, Flores-Mendoza L, Montoya M, Hernandez J (2010)

European genotype of porcine reproductive and respiratory syndrome (PRRSV) infects monocyte-derived dendritic cells but does not induce Treg cells

Virology 396 (2), 264-271
Publisher’s version: http://dx.doi.org/10.1016/j.virol.2009.10.024

Abstract

The aim of this study was to characterize the immune responses of DCs after infection with four different EU Strains of PRRSV and whether they show any ability to immunomodulate T cells activation. Our results show that all EU strains can efficiently infect and replicate in DCs. Nevertheless, SLA-II levels remained unaltered in DC infected by all EU PRRSV strains, whereas SLA-I expression was only reduced when strain 2992 was used. IL-10 production was induced by three EU PRRSV strains, being strain 2992 the highest inducer. However, no induction of Treg cells, measured by CD25 and Foxp3 expression on lymphocytes co-cultured with infected DCs, was found. TGF-beta induction was not detected in DC infected with any EU strain tested. In conclusion, DCs infected with EU PRRSV strains exhibited an unbalanced ability to stimulate T cell response and was strain dependent. However, Treg cells were not induced, at least in vitro.
Singh S M, Baigent S J, Petherbridge L J, Smith L P, Nair V K (2010)

Comparative efficacy of BAC-derived recombinant SB-1 vaccine and the parent wild type strain in preventing replication, shedding and disease induced by virulent Marek’s disease virus

Research in Veterinary Science 89 (1), 140-145
Publisher’s version: http://dx.doi.org/10.1016/j.rvsc.2010.01.010

Abstract

A widely used vaccine against Marek's disease (MD) in poultry is the virus SB-1, which is antigenically-related to the causative agent, Marek's disease herpesvirus. We recently cloned the SB-1 genome as an infectious bacterial artificial chromosome, BAC, (pSB-1). The protective efficacies and replication kinetics of pSB-1 and the parent strain (SB-1) were compared in an experimental model of MD induced by a virulent strain, RB-1B. Although vaccine virus replication and shedding was lower for pSB-1 than for SB-1, both vaccines reduced replication and shedding of RB-1B, and were equally effective in protecting chickens against MD. With the cloning of pSB-1, we have now generated full length genomic clones of MD vaccine virus strains belonging to each of the three serotypes. Vaccine viruses derived from each of these clones demonstrated protective efficacies at levels similar to those produced by the respective parent viruses, demonstrating their suitability to be used as vaccine candidates.
Sitthidet C, Stevens J M, Field T R, Layton A N, Korbsrisate S, Stevens M P (2010)

Actin-based motility of Burkholderia thailandensis requires a central acidic domain of BimA that recruits and activates the cellular Arp2/3 complex

Journal of Bacteriology 192 (19), 5249-5252
Publisher’s version: http://dx.doi.org/10.1128/JB.00608-10

Abstract

Burkholderia species use BimA for intracellular actin-based motility. Uniquely, Burkholderia thailandensis BimA harbors a central and acidic (CA) domain. The CA domain was required for actin-based motility, binding to the cellular Arp2/3 complex, and Arp2/3-dependent polymerization of actin monomers. Our data reveal distinct strategies for actin-based motility among Burkholderia species.
Sun A J, Xu X Y, Petherbridge L, Zhao Y G, Nair V, Cui Z Z (2010)

Functional evaluation of the role of reticuloendotheliosis virus long terminal repeat (LTR) integrated into the genome of a field strain of Marek's disease virus

Virology 397 (2), 270-276
Publisher’s version: http://dx.doi.org/10.1016/j.virol.2009.11.017

Abstract

MDV-GX0101 is a field strain of Marek's disease virus with a naturally occurring insertion of the reticuloendotheliosis virus (REV) LTR fragment. In order to study the biological properties of REV-LTR insertion in the MDV genome, we constructed a full-length infectious BAC clone of MDV-GX0101 strain and deleted the LTR sequences by BAC mutagenesis. The pathogenic properties of the LTR-deleted virus were evaluated in infected SPF birds. The study demonstrated that the LTR-deleted virus had a stronger inhibitory effect on the growth rates of the infected birds and induced stronger immunosuppressive effects. Surprisingly, however, the ability for horizontal transmission of the LTR-deleted virus appeared to be significantly weaker than its parental LTR-intact virus. Even though the precise molecular mechanisms are still not clear, the results of our studies demonstrate that the retention of the REV-LTR in the MDV genome decreases its pathogenic effects but increases its potential for horizontal transmission.
Szmaragd C, Gunn G J, Gubbins S (2010)

Assessing the consequences of an incursion of a vector-borne disease. II. Spread of bluetongue in Scotland and impact of vaccination

Epidemics 2 (3), 139-147
Publisher’s version: http://dx.doi.org/10.1016/j.epidem.2010.05.002

Abstract

Bluetongue is a viral disease of ruminants transmitted by Culicoides biting midges, which has spread across Europe over the past decade. The disease arrived in south-east England in 2007, raising the possibility that it could pose a risk to the valuable Scottish livestock industry. As part of an assessment of the economic consequences of a bluetongue virus incursion into Scotland commissioned by Scottish Government, we investigated a defined set of feasible incursion scenarios under different vaccination strategies. Our epidemiological simulations, based on expert knowledge, highlighted that infection will rarely spread in Scotland after the initial incursion and will be efficiently controlled by vaccination.
Szmaragd C, Wilson A J, Carpenter S, Wood J L, Mellor P S, Gubbins S (2010)

The spread of bluetongue virus serotype 8 in Great Britain and its control by vaccination

PLoS One 5 (2), e9353
Publisher’s version: http://dx.doi.org/10.1371/journal.pone.0009353

Abstract

Background: Bluetongue (BT) is a viral disease of ruminants transmitted by Culicoides biting midges and has the ability to spread rapidly over large distances. In the summer of 2006, BTV serotype 8 (BTV-8) emerged for the first time in northern Europe, resulting in over 2000 infected farms by the end of the year. The virus subsequently overwintered and has since spread across much of Europe, causing tens of thousands of livestock deaths. In August 2007, BTV-8 reached Great Britain (GB), threatening the large and valuable livestock industry. A voluntary vaccination scheme was launched in GB in May 2008 and, in contrast with elsewhere in Europe, there were no reported cases in GB during 2008. Methodology/Principal Findings: Here, we use carefully parameterised mathematical models to investigate the spread of BTV in GB and its control by vaccination. In the absence of vaccination, the model predicted severe outbreaks of BTV, particularly for warmer temperatures. Vaccination was predicted to reduce the severity of epidemics, with the greatest reduction achieved for high levels (95%) of vaccine uptake. However, even at this level of uptake the model predicted some spread of BTV. The sensitivity of the predictions to vaccination parameters (time to full protection in cattle, vaccine efficacy), the shape of the transmission kernel and temperature dependence in the transmission of BTV between farms was assessed. Conclusions/Significance: A combination of lower temperatures and high levels of vaccine uptake (>80%) in the previously-affected areas are likely to be the major contributing factors in the control achieved in England in 2008. However, low levels of vaccination against BTV-8 or the introduction of other serotypes could result in further, potentially severe outbreaks in future
Belhouchet M, Mohd Jaafar F, Tesh R, Grimes J, Maan S, Mertens P P C, Attoui H (2010)

Complete sequence of Great Island virus and comparison with the T2 and outer-capsid proteins of Kemerovo, Lipovnik and Tribec viruses (genus Orbivirus, family Reoviridae)

Journal of General Virology 91 (12), 2985-2993
Publisher’s version: http://dx.doi.org/10.1099/vir.0.024760-0

Abstract

The complete nucleotide sequence of Great Island virus (GIV) genome was determined, along with genome segments (Seg) 1, 2 and 6 of Kemerovo (KEMV), Lipovnik (LIPV) and Tribec (TRBV) viruses All four viruses, together with Broadhaven virus, are currently classified within the species Great Island virus and have been isolated from ticks, birds or humans Sequence comparisons showed that Seg-4 of GIV encoded the outer-capsid protein responsible for cell attachment, although it was approximately half the length of its counterpart in the Culicoides or mosquito-transmitted orbiviruses A second overlapping ORF (in the +2 reading frame) was identified in Seg-9 of GIV, encoding a putative dsRNA-binding protein Phylogenetic analyses of the RNA-dependent RNA polymerase (Pal) and 12 protein amino acid sequences indicated that the tick-borne orbiviruses represent an ancestral group from which the mosquito-borne orbiviruses have evolved This mirrors the evolutionary relationships between the arthropod vectors of these viruses, supporting a co-speciation hypothesis for these arboviruses and their arthropod-vectors Phylogenetic analyses of the 12 proteins of KEMV, LIPV, TRBV and GIV (showing 82% amino acid identity) correlated with the early classification of Great Island viruses as two distinct serocomplexes (Great Island and Kemerovo serocomplexes) Amino acid identity levels in the VP1(Pol) and T2 proteins between the two serocomplexes were 73 and 82%, respectively, whilst those between previously characterized Orbivirus species are 53-73% and 26-83%, respectively These data suggest that despite limited genome segment reassortment between these two groups, their current classification within the same Orbivirus species could be re-evaluated
Botner A, Pena A E, Mannelli A, Wieland B, Potzsch C, Patta C, Albina E, Boinas F, Koenen F, Sharp J M, Dixon L, Salman M, Sanchex V, Blome S, Guberti V, Dhollander S, Georgiev M, Tarres J, Goumperis T (2010)

Scientific opinion on African swine fever

EFSA Journal 8 (3), 1556 [149 pp.]
Publisher’s version: http://dx.doi.org/10.2903/j.efsa.2010.1556

Abstract

The risk that African Swine Fever virus (ASFV) remains endemic in the Trans Caucasian Countries (TCC) and the Russian Federation (RF) is moderate, while the risk of its spread in these regions is high. The resulting risk of introduction from these regions into the EU is moderate most likely through food waste. The risk of ASFV remaining endemic in wild boar and the consequent introduction into the EU was considered low in the TCC and moderate in the RF, mainly due to the higher population density in the RF and the connected wild boar populations to the EU from the RF. Within the EU, mainly domestic pigs in the free range (FR) and the limited biosecurity sector (LB) are likely to be exposed to ASFV via swill feeding, with low risk. Once infected, the risk of spread from the LB and FR sectors prior detection is high, mainly due to movement of pigs, people and vehicles and moderate from the High Biosecurity (HB) sector. The risk of endemicity in domestic pigs is considered negligible in HB and low in LB since the implementation of control measures are effective. The risk of endemicity in the FR sector is moderate due to wild boar contact, non-compliance with animal movement ban and difficult access to all individual pigs. The risk of ASFV becoming endemic in the wild boar population in the EU is moderate, in particular in areas with connected wild boar populations. Because of their long life, ticks of the O. erraticus complex can be important in maintaining local foci of ASFV, where pigs are kept under traditional systems. Ticks do not, play an active role in the geographical spread of the virus. Wild boar have never been found infested because they do not rest inside burrows potentially infested by ticks.

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