Publications

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

There were a total of 1605 results for your search.
Dunn J R, Reddy S M, Niikura M, Nair V, Fulton J E, Cheng H H (2017)

Evaluation and identification of Marek's disease virus BAC clones as standardized reagents for research

Avian Diseases 61 (1), 107-114

Abstract

Marek's disease virus (MDV) is an alphaherpesvirus that causes Marek's disease (MD), a lymphoproliferative disease in chickens. Understanding of MDV gene function advanced significantly following the cloning of the MDV genome as either a series of overlapping cosmids or as a bacterial artificial chromosome (BAC), both of which could produce viable MDV. The objectives of this study were to compare multiple virulent MDV BAC clones using the Avian Disease and Oncology Laboratory's pathotyping assay, and to demonstrate the use of these clones as standardized reagents for a modified pathotyping assay by other laboratories. To date, MDV BAC clones have been produced for at least 10 MDV strains from all three serotypes including several virulent serotype 1 strains. We determined that MDV BAC clones exist for each virulent pathotype, despite the fact that these clones are not always equal in virulence to their corresponding parental strains. One clone from each pathotype was further evaluated in commercial specific-pathogen-free (SPF) chickens and found suitable for use in assays such as best-fit pathotyping, although results were variable based on the source of the SPF birds. The benefits of using BAC clones, which include easy shipping, ability to more easily manipulate, and long-term ability to use at a low passage level, are likely to result in the use of BAC clones as standard reagents for MD research. The use of the defined set of clones should allow side-by-side comparison, allowing researchers to better interpret results produced in different laboratories using different MDV field strains. Furthermore, a modified best-fit pathotyping assay has been proposed using these clones and reduced bird numbers.

Clarke B, Mahapatra M, Friedgut O, Bumbarov V, Parida S (2017)

Persistence of lineage IV peste-des-petits ruminants virus within Israel since 1993: an evolutionary perspective

PLOS ONE 12 (5), e0177028

Abstract

Peste-des-petits ruminants (PPR) is one of the most important infectious diseases of domesticated small ruminants. From the initial identification in 1942 in West Africa, PPR virus (PPRV) has spread throughout much of the developing world. PPRV is now considered endemic throughout Africa, with the notable exception of South Africa, the Middle-East and Israel, as well as South-, East-, and Central Asia. Despite this widespread dispersal, the evolution and transmission of PPRV in endemic populations is not well understood. This understanding will be critical in the planning of rational measures to eradicate PPRV by the planned time as defined by the FAO and OIE. To further advance the understanding of the evolution of PPRV the full genome sequence of 18 viruses isolated from Israel from consecutive years between 1997–2014 were generated. This data set is unique and crucial for the understanding of the evolution of PPRV, as it represents the first set of full-length sequence data available from consecutive years from a single geographic location. Analysis of these full genome sequences shows 96.2–99.9% nucleotide conservation across the Israel isolates and further demonstrates the strong purifying selection pressures on PPRV within Israel and globally. Four amino acid substitutions indicative of putative positive selection were additionally identified within the Israel isolates. The mean substitution rate per site per year was estimated to be 9.22 x 10?4 (95% HPD 6.206 x 10?4–1.26 x 10?3). Using Bayesian and phylogenetic analyses we further demonstrate that the PPRV isolates from Israel belongs to linage IV and form a single strong regional cluster within all other lineage IV viruses circulating worldwide implying a single incursion into Israel.

Bassano I, Ong S H, Lawless N, Whitehead T, Fife M, Kellam P (2017)

Accurate characterization of the IFITM locus using MiSeq and PacBio sequencing shows genetic variation in Galliformes

BMC Genomics 18 (1), 419

Abstract

Interferon inducible transmembrane (IFITM) proteins are effectors of the immune system widely characterized for their role in restricting infection by diverse enveloped and non-enveloped viruses. The chicken IFITM (chIFITM) genes are clustered on chromosome 5 and to date four genes have been annotated, namely chIFITM1, chIFITM3, chIFITM5 and chIFITM10. However, due to poor assembly of this locus in the Gallus Gallus v4 genome, accurate characterization has so far proven problematic. Recently, a new chicken reference genome assembly Gallus Gallus v5 was generated using Sanger, 454, Illumina and PacBio sequencing technologies identifying considerable differences in the chIFITM locus over the previous genome releases.

Peacock T P, Benton D J, James J, Sadeyen J-R, Chang P, Sealy J E, Bryant J E, Martin S R, Shelton H, Barclay W S, Iqbal M (2017)

Immune escape variants of H9N2 influenza viruses containing deletions at the haemagglutinin receptor binding site retain fitness in vivo and display enhanced zoonotic characteristics

Journal of Virology 91 (14), e00218-17

Abstract

H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa where they pose a threat to human health, both as zoonotic agents and as potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions, however vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza antigen, haemagglutinin (HA). Using selection with HA specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBS). Here, we analysed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that the mutant viruses with RBS deletions are able to escape polyclonal antisera binding and are able to infect and transmit between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells, however the mutant HAs also displayed a reduced pH and thermal stability. In summary we infer that variant influenza viruses with deletions in 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude these viruses would be unlikely to transmit human-to-human by an airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses, as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence.IMPORTANCE Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden, however, influenza viruses are able to rapidly evolve to escape immune pressure in a process known as ‘antigenic drift’. Previously we experimentally generated antigenic drift variants in the laboratory, and here we test our ‘drifted’ viruses to assess their zoonotic infection characteristics and transmissibility in chickens. We found that the ‘drifted’ viruses were able to infect and transmit between chickens and showed increased binding to human-like receptors. However the ‘drift’ mutant viruses displayed reduced stability and, we predict, would be unlikely to be able to transmit human-to-human and cause an influenza pandemic. These results demonstrate the complex relationship between antigenic drift and potential of avian influenza viruses to infect humans.

Kotecha A, Wang Q, Dong X, Ilca S L, Ondiviela M, Zihe R, Seago J, Charleston B, Fry E E, Abrescia N G A, Springer T A, Huiskonen J T, Stuart D I (2017)

Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus

Nature Communications 8, 15408

Abstract

Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally alphavbeta6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections. HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding. Here we determined the interaction between alphavbeta6 and two tissue culture adapted FMDV strains by cryo-electron microscopy. In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues. In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.

Yinda C K, Zell R, Deboutte W, Zeller M, Conceição-Neto N, Heylen E, Maes P, Knowles N J, Ghogomu S M, Van Ranst M, Matthijnssens J (2017)

Highly diverse population of Picornaviridae and other members of the Picornavirales, in Cameroonian fruit bats

BMC Genomics 18 (1), 249

Abstract

The order Picornavirales represents a diverse group of positive-stranded RNA viruses with small non-enveloped icosahedral virions. Recently, bats have been identified as an important reservoir of several highly pathogenic human viruses. Since many members of the Picornaviridae family cause a wide range of diseases in humans and animals, this study aimed to characterize members of the order Picornavirales in fruit bat populations located in the Southwest region of Cameroon. These bat populations are frequently in close contact with humans due to hunting, selling and eating practices, which provides ample opportunity for interspecies transmissions.

Sumner T, Orton R J, Green D M, Kao R R, Gubbins S (2017)

Quantifying the roles of host movement and vector dispersal in the transmission of vector-borne diseases of livestock

PLOS Computational Biology 13 (4), e1005470

Abstract

Diseases which are transmitted by the bites of insects can be spread to new locations through the movement of both infected insects and infected hosts. The importance of these routes has implications for disease control, because we can often restrict host movement, and so potentially reduce spread, but cannot easily restrict insect movements. Despite this, the importance of host movements has been little studied. Here we develop a mathematical model which allows us to disentangle and quantify transmission by insect dispersal and by host movement. We apply the model to two diseases of cattle and sheep transmitted by biting midges that have emerged in northern Europe in the past decade, bluetongue virus (BTV) and Schmallenberg virus (SBV). For both viruses, we show insect movements account for a majority of spread between farms. Although they cannot sustain an epidemic on their own, animal movements play an important role in introducing disease to new areas.

Souley Kouato B, Elliot F M, King D P, Hyera J, Knowles N J, Ludi A B, Mioulet V, Matlho G, De Clercq K, Thys E, Marichatou H, Issa S, Saegerman C (2017)

Outbreak investigations and molecular characterization of foot-and-mouth disease viruses circulating in south-west Niger

Transboundary and Emerging Diseases early view,

Abstract

In Niger, the epidemiological situation regarding foot-and-mouth disease is unclear as many outbreaks are unreported. This study aimed (i) to identify Foot-and-mouth disease virus (FMDV) strains currently circulating in cattle herds, and (ii) to identify risk factors associated with Foot-and-mouth disease (FMD)-seropositive animals in clinical outbreaks. Epithelial tissues (n = 25) and sera (n = 227) were collected from cattle in eight districts of the south-western part of Niger. Testing of clinical material revealed the presence of FMDV serotype O that was characterized within the O/WEST AFRICA topotype. The antigenic relationship between one of the FMDV isolates from Niger (O/NGR/4/2015) and three reference vaccine strains was determined by the two-dimensional virus neutralization test (2dmVNT), revealing a close antigenic match between the field isolate from Niger and three FMDV serotype O vaccine strains. Serological analyses using a non-structural protein (NSP) test provided evidence for previous FMDV infection in 70% (158/227) of the sera tested. Multivariate logistic regression analysis revealed that only the herd composition (presence of both cattle and small ruminants) was significantly associated with FMDV seropositivity as defined by NSP-positive results (p-value = .006). Of these positive sera, subsequent testing by liquid-phase blocking ELISA (LPBE) showed that 86% (136/158) were positive for one (or more) of four FMDV serotypes (A, O, Southern African Territories (SAT) 1 and SAT 2). This study provides epidemiological information about FMD in the south-western part of Niger and highlights the complex transboundary nature of FMD in Africa. These findings may help to develop effective control and preventive strategies for FMD in Niger as well, as other countries in West Africa.

Scott K A, Kotecha A, Seago J, Ren J, Fry E E, Stuart D I, Charleston B, Maree F F (2017)

SAT2 foot-and-mouth disease virus (FMDV) structurally modified for increased thermostability

Journal of Virology 91 (10),

Abstract

Foot-and-mouth disease virus (FMDV) is notoriously unstable, particularly the O and SAT serotypes. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of poor duration immunity and hence require more frequent vaccinations to ensure protection. In-silico calculations predicted residue substitutions that would increase interactions at the inter-pentameric interface supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses for their growth kinetics; antigenicity; plaque morphology; genetic stability; temperature, ionic and pH stability using the thermofluor and inactivation assays, in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutation was the single mutant S2093Y for temperature and pH stability, whilst other promising single mutants were E3198A, L2094V,S2093H and the triple mutant F2062Y-H2087M-H3143V. Although the S2093Y mutant had the greatest stability it exhibited smaller plaques; a reduced growth rate; a change in a monoclonal antibody footprint, and poor genetic stability properties compared to the wild-type virus. However, these factors affecting production can be overcome. The addition of 1M NaCl salt was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilising SAT2 vaccines.IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of serotypes such as SAT2 affects the quality of the vaccine and therefore the duration of immunity. We have shown that by mutating residues at the capsid interface through predictive modelling we can improve the stability of SAT2 viruses. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in endemic countries that rely heavily on the maintenance of the cold-chain, with potential improvement to the duration of immune responses.

Piaggio A J, Segelbacher G, Seddon P J, Alphey L, Bennett E L, Carlson R H, Friedman R M, Kanavy D, Phelan R, Redford K H, Rosales M, Slobodian L, Wheeler K (2017)

Is it time for synthetic biodiversity conservation?

Trends in Ecology and Evolution 32 (2), 97-107

Abstract

Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.

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