Publications

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

There were a total of 2026 results for your search.

Abstract

African swine fever (ASF) poses a severe threat to the global pig industry for which currently there is no available vaccine. The aetiological ASF virus (ASFV) has a predilection for cells of the myeloid lineage, however little is known about its interaction with polarised macrophages. This study focused on the in vitro interactions of porcine monocyte-derived un-activated (moMΦ), classically (moM1), alternatively (moM2), and IFN-a-activated macrophages with two genotype I ASFV strains: virulent 22653/14 and attenuated NH/P68. At a high multiplicity of infection, NH/P68, but not 22653/14, presented a reduced ability to infect moM1 and IFN-a-activated moMF compared to moMF. IFN-a activation resulted in a dose-dependent reduction in the proportion of ASFV-infected cells. Both strains replicated efficiently in all the subsets. While higher levels of IL-1a, IL-1β, and IL-18 were secreted by NH/P68-infected moM1 compared to 22653/14, both strains negatively affected moMF ability to release IL-6, IL-12, TNF-a in response to classical activation or stimulation with a TLR2 agonist. Our results suggest that ASFV 22653/14 covertly replicates in macrophages, compromising the development of effective immune responses. Attenuated NH/P68 has partially lost these mechanisms, which may enhance immune surveillance. A better understating of these mechanisms should aid the rational design of live attenuated ASFV vaccines. 

Fine A E, Pruvot M, Benfield C, Caron A, Cattoli G, Chardonnet P, Dioli M, Dulu T, Gilbert M, Kock R A, Mariner J C, Ostrowski S, Parida S, Fereidouni S, Shiilegdamba E, Sleeman J, Schulz C, Soula J-J, Van der Stede Y, Tekola B G, Walzer C, Njeumi F (2020)

Eradication of peste des petits ruminants virus and the wildlife-livestock interface

Frontiers in Veterinary Science 7, 50

Abstract

There is growing evidence that multiple wildlife species can be infected with peste des petits ruminants virus (PPRV). This has important consequences for the potential maintenance of PPRV in communities of susceptible hosts, and the threat that PPRV may pose to the conservation of wildlife populations and resilience of ecosystems. Significant knowledge gaps in the epidemiology of PPRV across the ruminant community (wildlife and domestic), and understanding of the infection in wildlife and other atypical host species groups (e.g. camelidae, suidae, and bovinae) hinders our ability to apply necessary integrated disease control and management interventions at the wildlife-livestock interface. Similarly, knowledge gaps limit the inclusion of wildlife in the FAO/OIE Global Strategy for the Control and Eradication of PPR, and the framework of activities in the PPR Global Eradication Programme that lays the foundation for eradicating PPR through national and regional efforts. This article reports on the first international meeting on, “Controlling PPR at the livestock-wildlife interface”, held in Rome, Italy, March 27-29, 2019. A large group representing national and international institutions discussed recent advances in our understanding of PPRV in wildlife, identified knowledge gaps and research priorities, and formulated recommendations. The need for a better understanding of PPRV epidemiology at the wildlife-livestock interface to support the integration of wildlife into PPR eradication efforts was highlighted by meeting participants along with the reminder that PPR eradication and wildlife conservation need not be viewed as competing priorities, but should instead constitute two requisites of healthy socio-ecological systems. 

Fernandez Aguilar X, Mahapatra M, Begovoeva M, Kalema-Zikusoka G, Driciru M, Ayebazibwe C, Adwok D S, Kock M, Lukusa J-P K, Muro J, Marco I, Colom-Cadena A, Espunyes J, Meunier N, Cabezón O, Caron A, Bataille A, Libeau G, Parekh K, Parida S, Kock R (2020)

Peste des petits ruminants at the wildlife–livestock interface in the Northern Albertine Rift and Nile Basin, East Africa

Viruses 12 (3), 293
Publisher’s version: https://doi.org/10.3390/v12030293

Abstract

In the recent past, peste des petits ruminants (PPR) emerged in East Africa causing outbreaks in small livestock across different countries, with evidences of spillover to wildlife. In order to understand better PPR at the wildlife–livestock interface, we investigated patterns of peste des petits ruminants virus (PPRV) exposure, disease outbreaks, and viral sequences in the northern Albertine Rift. PPRV antibodies indicated a widespread exposure in apparently healthy wildlife from South Sudan (2013) and Uganda (2015, 2017). African buffaloes and Uganda kobs <1-year-old from Queen Elizabeth National Park (2015) had antibodies against PPRV N-antigen and local serosurvey captured a subsequent spread of PPRV in livestock. Outbreaks with PPR-like syndrome in sheep and goats were recorded around the Greater Virunga Landscape in Kasese (2016), Kisoro and Kabale (2017) from western Uganda, and in North Kivu (2017) from eastern Democratic Republic of the Congo (DRC). This landscape would not be considered typical for PPR persistence as it is a mixed forest–savannah ecosystem with mostly sedentary livestock. PPRV sequences from DRC (2017) were identical to strains from Burundi (2018) and confirmed a transboundary spread of PPRV. Our results indicate an epidemiological linkage between epizootic cycles in livestock and exposure in wildlife, denoting the importance of PPR surveillance on wild artiodactyls for both conservation and eradication programs

England M E, Pearce-Kelly P, Brugman V A, King S, Gubbins S, Sach F, Sanders C J, Masters N J, Denison E, Carpenter S (2020)

Culicoides species composition and molecular identification of host blood meals at two zoos in the UK

Parasites and Vectors 13, 139

Abstract

Culicoides biting midges are biological vectors of arboviruses including bluetongue virus (BTV), Schmallenberg virus (SBV) and African horse sickness virus (AHSV). Zoos are home to a wide range of ‘at risk’ exotic and native species of animals. These animals have a high value both in monetary terms, conservation significance and breeding potential. To understand the risk these viruses pose to zoo animals, it is necessary to characterise the Culicoides fauna at zoos and determine which potential vector species are feeding on which hosts.

Abstract

CRISPR-based gene drives bias inheritance in their favour by inducing double-stranded breaks (DSBs) at wild-type homologous loci and using the drive transgene as a repair template – converting drive heterozygotes into homozygotes. Recent studies have shown that alternate end-joining repair mechanisms produce cut-resistant alleles that rapidly induce drive failure. Multiplexing – simultaneously targeting multiple sites at the wild-type locus – is commonly assumed to overcome this issue since resistance would need to develop at all target sites for the system to fail. This may work for some population suppression drives targeting essential (e.g. viability or fertility) genes if careful design can ensure cut-resistant alleles themselves have low fitness. However, here, models are used to demonstrate that this approach will be ineffective when targeting neutral loci. We then go on to compare the performance of four alternative population level multiplexing approaches with standard individual level multiplexing. Two of these approaches have mechanisms preventing them from becoming linked, thus avoiding multiple simultaneous DSBs and giving a large improvement. Releasing multiple unlinked drives gives a modest improvement while releasing multiple drives that may become linked over time produces a decrease in performance under the conditions tested here. Based on performance and technical feasibility we then take one approach forward for further investigation, demonstrating its robustness to different performance parameters and its potential for controlling very large target populations.

Combrink L, Glidden C K, Beechler B R, Charleston B, Koehler A V, Sisson D, Gasser R B, Jabbar A, Jolles A E (2020)

Age of first infection across a range of parasite taxa in a wild mammalian population

Biology Letters 16 (2), 20190811

Abstract

Newborn mammals have an immature immune system that cannot sufficiently protect them against infectious diseases. However, variation in the effectiveness of maternal immunity against different parasites may couple with temporal trends in parasite exposure to influence disparities in the timing of infection risk. Determining the relationship between age and infection risk is critical in identifying the portion of a host population that contributes to parasite dynamics, as well as the parasites that regulate host recruitment. However, there are no data directly identifying timing of first infection among parasites in wildlife. Here, we took advantage of a longitudinal dataset, tracking infection status by viruses, bacteria, protists and gastro-intestinal worms in a herd of African buffalo (Syncerus caffer) to ask: how does age of first infection differ among parasite taxa? We found distinct differences in the age of first infection among parasites that aligned with the mode of transmission and parasite taxonomy. Specifically, we found that tick-borne and environmentally transmitted protists were acquired earlier than directly transmitted bacteria and viruses. These results emphasize the importance of understanding infection risk in juveniles, especially in host species where juveniles are purported to sustain parasite persistence and/or where mortality rates of juveniles influence population dynamics.

Cackett G, Matelska D, Sýkora M, Portugal R, Malecki M, Bähler J, Dixon L, Werner F (2020)

The African swine fever virus transcriptome

Journal of Virology Early view

Abstract

African Swine Fever Virus (ASFV) causes haemorrhagic fever in domestic pigs, presenting the biggest global threat to animal farming in recorded history. Despite its importance, little is known about the mechanisms and regulation of ASFV transcription. Using RNA sequencing methods, we have determined total RNA abundance, transcription start sites and transcription termination sites at single nucleotide-resolution. This allowed us to characterise DNA consensus motifs of early and late ASFV core promoters, as well as a poly-thymidylate sequence determinant for transcription termination. Our results demonstrate that ASFV utilises alternative transcription start sites between early and late stages of infection, and that ASFV-RNAP undergoes promoter-proximal transcript slippage at 5′ ends of transcription units, adding quasi templated AU- and AUAU-5′ extensions to mRNAs. Here we present the first much-needed genome-wide transcriptome study that provides unique insight into ASFV transcription and serves as a resource to aid future functional analyses of ASFV genes which are essential to combat this devastating disease.ImportanceAfrican swine fever virus (ASFV) causes incurable and often lethal haemorrhagic fever in domestic pigs. In 2019, ASF presents an acute and global animal health emergency that has the potential to devastate entire national economies as effective vaccines or antiviral drugs are not currently available (Food and Agriculture Organization of the UN). With major outbreaks ongoing in Eastern Europe and Asia urgent action is needed to advance our knowledge about the fundamental biology of ASFV, including the mechanisms and temporal control of gene expression. A thorough understanding of RNAP and transcription factor function, and the sequence context of their promoter motifs, as well as accurate knowledge of which genes are expressed when and the amino acid sequence of the encoded proteins, is direly needed for the development of antiviral drugs and vaccines.

Abstract

Understanding of the biology of foot-and-mouth disease virus (FMDV) has grown considerably since the nucleotide sequence of the viral RNA was determined. The ability to manipulate the intact genome and also to express specific parts of the genome individually has enabled detailed analyses of viral components, both RNA and protein. Such studies have identified the requirements for specific functional elements for virus replication and pathogenicity. Furthermore, information about the functions of individual virus proteins has enabled the rational design of cDNA cassettes to express non-infectious empty capsid particles that can induce protective immunity in the natural host animals and thus represent new vaccine candidates. Similarly, attempts to block specific virus activities using antiviral agents have also been performed. However, currently, only the well-established, chemically inactivated FMDV vaccines are commercially available and suitable for use to combat this important disease of livestock animals. These vaccines, despite certain shortcomings, have been used very successfully (e.g. in Europe) to control the disease but it still remains endemic in much of Africa, southern Asia and the Middle East. Hence there remains a significant risk of reintroduction of the disease into highly susceptible animal populations with enormous economic consequences.

Abstract

Introduction: The effectiveness of formaldehyde as a fumigant in laboratories, for equipment, and for containment barrier decontamination applications was assessed, in particular the ability to reproduce biological inactivation (6-log reduction) of commercially available rapid biological indicators in representative operational scenarios and their relative sensitivity to other biological and chemical indicators.  Objectives: The primary objective of this study was to describe observations and results of formaldehyde fumigation efficacy in high containment laboratories.  Results: Biological indicators placed throughout laboratory spaces, including ventilation ductwork at distances up to 15 meters, inside pieces of equipment and in lengths of pipe, were mostly negative, demonstrating the ability of formaldehyde to reach the interior and external surfaces tested. Dwell times as short as 10 minutes were shown to be sufficient in barrier decontamination equipment for the fumigation of personal computers. Furthermore, a pipework bore:length ratio of 1:1500 was proven too great a challenge. Indicators placed after extracting HEPA filters in microbiological safety cabinets (MBSCs) were also successfully fumigated (at room temperature) relying solely on diffusion and in the cabinet workspace at 10°C to 12°C. In addition, pressures of up to 900 Pa were experienced in low-leakage laboratory spaces during fumigation.  Conclusions: Formaldehyde fumigation was shown to be effective in a variety of scenarios representing operational activities thereby giving process assurance.

Simmonds P, Gorbalenya A E, Harvala H, Hovi T, Knowles N J, Lindberg A M, Oberste M S, Palmenberg A C, Reuter G, Skern T, Tapparel C, Wolthers K C, Woo P C Y, Zell R (2020)

Recommendations for the nomenclature of enteroviruses and rhinoviruses

Archives of Virology Early view

Abstract

Enteroviruses (EVs) and rhinoviruses (RVs) are significant pathogens of humans and are the subject of intensive clinical and epidemiological research and public health measures, notably in the eradication of poliovirus and in the investigation and control of emerging pathogenic EV types worldwide. EVs and RVs are highly diverse in their antigenic properties, tissue tropism, disease associations and evolutionary relationships, but the latter often conflict with previously developed biologically defined terms, such as "coxsackieviruses", "polioviruses" and "echoviruses", which were used before their genetic interrelationships were understood. This has created widespread formatting problems and inconsistencies in the nomenclature for EV and RV types and species in the literature and public databases. As members of the International Committee for Taxonomy of Viruses (ICTV) Picornaviridae Study Group, we describe the correct use of taxon names for these viruses and have produced a series of recommendations for the nomenclature of EV and RV types and their abbreviations. We believe their adoption will promote greater clarity and consistency in the terminology used in the scientific and medical literature. The recommendations will additionally provide a useful reference guide for journals, other publications and public databases seeking to use standardised terms for the growing multitude of enteroviruses and rhinoviruses described worldwide.

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