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

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Sanz-Bernardo B, Haga I R, Wijesiriwardana N, Hawes P C, Simpson J, Morrison L R, MacIntyre N, Brocchi E, Atkinson J, Haegeman A, De Clercq K, Darpel K E, Beard P M (2020)

Lumpy skin disease is characterized by severe multifocal dermatitis with necrotizing fibrinoid vasculitis following experimental infection

Veterinary Pathology 57 (3), 388-396


Lumpy skin disease is a high-consequence disease in cattle caused by infection with the poxvirus lumpy skin disease virus (LSDV). The virus is endemic in most countries in Africa and an emerging threat to cattle populations in Europe and Asia. As LSDV spreads into new regions, it is important that signs of disease are recognized promptly by animal caregivers. This study describes the gross, microscopic, and ultrastructural changes that occur over time in cattle experimentally challenged with LSDV. Four calves were inoculated with wildtype LSDV and monitored for 19 to 21 days. At 7 days after inoculation, 2 of the 4 cattle developed multifocal cutaneous nodules characteristic of LSD. Some lesions displayed a targetoid appearance. Histologically, intercellular and intracellular edema was present in the epidermis of some nodules. Occasional intracytoplasmic inclusion bodies were identified in keratinocytes. More severe and consistent changes were present in the dermis, with marked histiocytic inflammation and necrotizing fibrinoid vasculitis of dermal vessels, particularly the deep dermal plexus. Chronic lesions consisted of full-thickness necrosis of the dermis and epidermis. Lesions in other body organs were not a major feature of LSD in this study, highlighting the strong cutaneous tropism of this virus. Immunohistochemistry and electron microscopy identified LSDV-infected histiocytes and fibroblasts in the skin nodules of affected cattle. This study highlights the noteworthy lesions of LSDV and how they develop over time.

Hacioglu S, King S, Cizmeci S G, Yesil O, Flannery J, Baron M D, Batten C, Rajko-Nenow P Z (2020)

Complete genome sequence of a lineage IV peste des petits ruminants virus from Turkey, 2018

Microbiology Resource Announcements 9 (15), e01446-19


We report the whole-genome sequence of a peste des petits ruminants virus (PPRV) from a lamb exhibiting clinical signs in Turkey in September 2018. The genome of PPRV/Turkey/Central_Anatolia/2018 shows the highest nucleotide sequence identity (97.63%) to PPRV isolated in Turkey in 2000.


Following the successful eradication of rinderpest, the World Organization of Animal Health (OIE) and the Food and Agriculture Organization (FAO) have set a goal to eradicate peste des petits ruminants (PPR) globally by 2030. Vaccination is being taken forward as the key strategy along with epidemiological surveillance to target vaccination efforts and eradicate the disease. PPR is highly contagious and is generally spread by aerosolized droplets and close contact. Currently, two live attenuated vaccines (Nigeria 75/1 and Sungri 96) are in use, and administered subcutaneously to prevent transmission of PPR and protect vaccinated animals. Though the target cells that support primary replication of PPR vaccine strains are largely unknown, it is hypothesized that the immune response could be intensified following intranasal vaccine delivery as this route mimics the natural route of infection. This study aims to compare the immunogenicity and protective efficacy of the two currently available live attenuated PPR vaccines following subcutaneous and intranasal routes of vaccination in target species. Groups of five goats were vaccinated with live attenuated PPR vaccines (Nigeria 75/1 and Sungri 96) by either the subcutaneous or intranasal route, and 28 days later challenged intranasally with virulent PPR virus. All vaccinated animals regardless of vaccination route produced PPRV-specific antibodies post-vaccination. Following challenge, all goats were protected from clinical disease, and vaccination was considered to have induced sterilizing immunity. This study demonstrates that the intranasal route of vaccination is as effective as the subcutaneous route of vaccination when using available live attenuated PPR vaccines.


Peste des petits ruminants (PPR) disease was first confirmed in Tanzania in 2008 in sheep and goats in Ngorongoro District, northern Tanzania, and is now endemic in this area. This study aimed to characterise PPR disease in pastoralist small ruminant flocks in Ngorongoro District. During June 2015, 33 PPR-like disease reports were investigated in different parts of the district, using semi-structured interviews, clinical examinations, PPR virus rapid detection test (PPRV-RDT), and laboratory analysis. Ten flocks were confirmed as PPRV infected by PPRV-RDT and/or real-time reverse transcription-polymerase chain reaction (RT-qPCR), and two flocks were co-infected with bluetongue virus (BTV), confirmed by RT-qPCR. Phylogenetic analysis of six partial N gene sequences showed that the PPR viruses clustered with recent lineage III Tanzanian viruses, and grouped with Ugandan, Kenyan and Democratic Republic of Congo isolates. No PPR-like disease was reported in wildlife. There was considerable variation in clinical syndromes between flocks: some showed a full range of PPR signs, while others were predominantly respiratory, diarrhoea, or oro-nasal syndromes, which were associated with different local disease names (olodua—a term for rinderpest, olkipiei—lung disease, oloirobi—fever, enkorotik—diarrhoea). BTV co-infection was associated with severe oro-nasal lesions. This clinical variability makes the field diagnosis of PPR challenging, highlighting the importance of access to pen-side antigen tests and multiplex assays to support improved surveillance and targeting of control activities for PPR eradication. 


Cattle possess the most diverse repertoire of NK cell receptor genes among all mammals studied to date. Killer cell receptor genes encoded within the NK complex and killer cell Ig-like receptor genes encoded within the leukocyte receptor complex have both been expanded and diversified. Our previous studies identified two divergent and polymorphic KLRA alleles within the NK complex in the Holstein-Friesian breed of dairy cattle. By examining a much larger cohort and other ruminant species, we demonstrate the emergence and fixation of two KLRA allele lineages (KLRA*01 and -*02) at a single locus during ruminant speciation. Subsequent recombination events between these allele lineages have increased the frequency of KLRA*02 extracellular domains. KLRA*01 and KLRA*02 transcription levels contrasted in response to cytokine stimulation, whereas homozygous animals consistently transcribed higher levels of KLRA, regardless of the allele lineage. KLRA*02 mRNA levels were also generally higher than KLRA*01. Collectively, these data point toward alternative functional roles governed by KLRA genotype and allele lineage. On a background of high genetic diversity of NK cell receptor genes, this KLRA allele fixation points to fundamental and potentially differential function roles.


Marek’s disease is a major scourge challenging poultry health worldwide. It is caused by the highly contagious Marek’s disease virus (MDV), an alphaherpesvirus. Here, we showed that, similar to other members of its Herpesviridae family, MDV also presents a complex landscape of splicing events, most of which are uncharacterised and/or not annotated. Quite strikingly, and although the biological relevance of this fact is unknown, we found that a number of viral splicing isoforms are strain-specific, despite the close sequence similarity of the strains considered: very virulent RB-1B and vaccine CVI-988. We validated our findings by devising an assay that discriminated infections caused by the two strains in chicken embryonic fibroblasts on the basis of the presence of some RNA species. To our knowledge, this study is the first to accomplish such a result, emphasizing how relevant a comprehensive picture of the viral transcriptome is to fully understand viral pathogenesis.

Rosen B D, Bickhart D M, Schnabel R D, Koren S, Elsik C G, Tseng E, Rowan T N, Low W Y, Zimin A, Couldrey C, Hall R, Li W, Rhie A, Ghurye J, McKay S D, Thibaud-Nissen F, Hoffman J, Murdoch B M, Snelling W M, McDaneld T G, Hammond J A, Schwartz J C, Nandolo W, Hagen D E, Dreischer C, Schultheiss S J, Schroeder S G, Phillippy A M, Cole J B, Van Tassell C P, Liu G, Smith T P L, Medrano J F (2020)

De novo assembly of the cattle reference genome with single-molecule sequencing

GigaScience 19 (3), giaa021


Major advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10-12 years. These tools depend upon the Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies. We present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250x more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use. We demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species.


Peste des Petits Ruminants (PPR) is a highly contagious viral disease of both domestic (goats and sheep) and wild ruminants. Caused by a morbillivirus, that belongs to the family Paramyxoviridae. The disease is clinically and pathologically similar to rinderpest of cattle and human measles. PPR is one of the most economically devastating viral diseases of small ruminants. In April 2015, the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) launched the PPR Global Control and Eradication Strategy (PPR GCES) with the vision for global eradication by 2030. There is a strong and lasting international consensus to eradicate the disease in order to protect the livelihoods of the world's poorest populations. As with any disease, eradication is feasible when, policy, scientific and technical challenges are addressed. Ten majors challenges are described in this paper namely: understanding small ruminant production, facilitating research to support eradication, refining laboratory testing, improving epidemiological understanding of the virus, defining infection of wildlife and other species, optimizing vaccine delivery and novel vaccines, developing better control of animal movement, heightening serological monitoring, understanding socio-economic impact, and garnering funding and political will.


Diagnostic tests for foot-and-mouth disease (FMD) include the detection of antibodies against either the viral non-structural proteins or the capsid. The detection of antibodies against the structural proteins (SP) of the capsid can be used to monitor seroconversion in both infected and vaccinated animals. However, SP tests need to be tailored to the individual FMD virus serotype and their sensitivity performances may be affected by antigenic variability within each serotype and mismatching between tests reagents. As a consequence, FMD Reference Laboratories are required to maintain multiple type-specific SP assays and reagents. A universal SP test would simplify frontline diagnostics and facilitate large-scale serological surveillance and post-vaccination monitoring. In this study, a highly conserved region in the N terminus of FMDV capsid protein VP2 (VP2N) was characterised using a panel of intertypic-reactive monoclonal antibodies. This revealed a universal epitope in VP2N which could be used as a peptide antigen to detect FMDV-specific antibodies against all types of the virus. A VP2-peptide ELISA (VP2-ELISA) was optimised using experimental and reference antisera from immunized, convalescent and negative animals (n=172). The VP2-ELISA is universal, simple and provided sensitive (99 %) and specific (93%) detection of antibodies to all FMDV strains used in this study. We anticipate that this SP test could have utility for sero-surveillance during virus incursions in FMD-free countries and as an additional screening tool to assess FMD virus circulation in endemic countries.

Anderson M A E, Purcell J, Verkuijl S A N, Norman V C, Leftwich P T, Harvey-Samuel T, Alphey L S (2020)

Expanding the CRISPR toolbox in Culicine mosquitoes: in vitro validation of Pol III promoters

ACS Synthetic Biology 9 (3), 678-681


CRISPR-Cas9-based "gene drive" technologies have been proposed as a novel and effective means of controlling human diseases vectored by mosquitoes. However, more complex designs than those demonstrated to date-and an expanded molecular toolbox with which to build them-will be required to overcome the issues of resistance formation/evolution and drive spatial/temporal limitation. Foreseeing this need, we assessed the sgRNA transcriptional activities of 33 phylogenetically diverse insect Polymerase III promoters using three disease-relevant Culicine mosquito cell lines (Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus). We show that U6 promoters work across species with a range of transcriptional activity levels and find 7SK promoters to be especially promising because of their broad phylogenetic activity. We further show that U6 promoters can be substantially truncated without affecting transcriptional levels. These results will be of great utility to researchers involved in developing the next generation of gene drives.


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