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

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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.
Brenner J, Oura C, Asis I, Maan S, Elad D, Maan N, Friedgut O, Nomikou K, Rotenberg D, Bumbarov V, Mertens P, Yadin H, Batten C (2010)

Multiple serotypes of bluetongue virus in sheep and cattle, Israel. (Letter)

Emerging Infectious Diseases 16 (12), 2003-2004
Publisher’s version: http://dx.doi.org/10.3201/eid1612.100239
Buck A H, Perot J, Chisholm M A, Kumar D S, Tuddenham L, Cognat V, Marcinowski L, Dölken L, Pfeffer S (2010)

Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection

RNA 16 (2), 307-315
Publisher’s version: http://dx.doi.org/10.1261/rna.1819210

Abstract

In mammals, microRNAs (miRNAs) can play diverse roles in viral infection through their capacity to regulate both host and viral genes. Recent reports have demonstrated that specific miRNAs change in expression level upon infection and can impact viral production and infectivity. It is clear that miRNAs are an integral component of viral–host interactions, and it is likely that both host and virus contain mechanisms to regulate miRNA expression and/or activity. To date, little is known about the mechanisms by which miRNAs are regulated in viral infection. Here we report the rapid down-regulation of miR-27a in multiple mouse cell lines as well as primary macrophages upon infection with the murine cytomegalovirus. Down-regulation of miR-27a occurs independently from two other miRNAs, miR-23a and miR-24, located within the same genomic cluster, and analysis of pri-miRNA levels suggest that regulation occurs post-transcriptionally. miR-27b, a close homolog of miR-27a (20/21 nucleotide identity), also decreases upon infection, and we demonstrate that both miR-27a and miR-27b exert an antiviral function upon over-expression. Drug sensitivity experiments suggest that virus entry is not sufficient to induce the down-regulation of miR-27 and that the mechanism requires synthesis of RNA. Altogether, our findings indicate that miR-27a and miR-27b have antiviral activity against MCMV, and that either the virus or the host encodes molecule(s) for regulating miR-27 accumulation, most likely by inducing the rapid decay of the mature species.
Buckley A M, Wang J H, Hudson D L, Grant A J, Jones M A, Maskell D J, Stevens M P (2010)

Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter antigens for control of C. jejuni in poultry

Vaccine 28 (4), 1094-1105
Publisher’s version: http://dx.doi.org/10.1016/j.vaccine.2009.10.018

Abstract

Campylobacter jejuni is a zoonotic bacterial pathogen of worldwide importance. It is estimated that 460,000 human infections occur in the United Kingdom per annum and these involve acute enteritis and may be complicated by severe systemic sequelae. Such infections are frequently associated with the consumption of contaminated poultry meat and strategies to control C. jejuni in poultry are expected to limit pathogen entry into the food chain and the incidence of human disease. Toward this aim, a total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium ?aroA vaccine expressing the C. jejuni amino acid binding protein CjaA as a plasmid-borne fusion to the C-terminus of fragment C of tetanus toxin. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4 log10 colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA. Protection was not observed using a vaccine strain containing the empty plasmid. Vaccination with recombinant CjaA subcutaneously at the same intervals significantly reduced the caecal load of C. jejuni at three and four weeks post-challenge. Taken together these data imply that responses directed against CjaA, rather than competitive or cross-protective effects mediated by the carrier, confer protection. The impact of varying parameters on the efficacy of the S. Typhimurium ?aroA vaccine expressing TetC-CjaA was also tested. Delaying the age at primary vaccination had little impact on protection or humoral responses to CjaA. The use of the parent strain as carrier or changing the attenuating mutation of the carrier to ?spaS or ?ssaU enhanced the protective effect, consistent with increased invasion and persistence of the vaccine strains relative to the ?aroA mutant. Expression in the ?aroA strain of a TetC fusion to Peb1A, but not TetC fusions to GlnH or ChuA, elicited protection against intestinal colonisation by C. jejuni that was comparable to that observed with the TetC-CjaA fusion. Our data are rendered highly relevant by use of the target host in large numbers and support the potential of CjaA- and Peb1A-based vaccines for control of C. jejuni in poultry.

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