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

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Eye pigmentation genes have been utilized as visible markers for constructing genetic control prototypes in several insect vectors of human disease. Here, orthologs of two ommochrome pathway genes, kynurenine 3-hydroxylase (kmo) and cardinal, were investigated in Plutella xylostella, a globally distributed, economically important pest of Brassica crops.

Walker P J, Siddell S G, Lefkowitz E J, Mushegian A R, Adriaenssens E M, Dempsey D M, Dutilh B E, Harrach B, Harrison R L, Hendrickson R C, Junglen S, Knowles N J, Kropinski A M, Krupovic M, Kuhn J H, Nibert M, Orton R J, Rubino L, Sabanadzovic S, Simmonds P, Smith D B, Varsani A, Zerbini F M, Davison A J (2020)

Changes to virus taxonomy and the Statutes ratified by the International Committee on Taxonomy of Viruses (2020)

Archives of Virology early view


This article reports the changes to virus classification and taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2020. The entire ICTV was invited to vote on 206 taxonomic proposals approved by the ICTV Executive Committee at its meeting in July 2019, as well as on the proposed revision of the ICTV Statutes. All proposals and the revision of the Statutes were approved by an absolute majority of the ICTV voting membership. Of note, ICTV has approved a proposal that extends the previously established realm Riboviria to encompass nearly all RNA viruses and reverse-transcribing viruses, and approved three separate proposals to establish three realms for viruses with DNA genomes.

Teem J L, Alphey L, Descamps S, Edgington M P, Edwards O, Gemmell N, Harvey-Samuel T, Melnick R L, Oh K P, Piaggio A J, Saah J R, Schill D, Thomas P, Smith T, Roberts A (2020)

Genetic biocontrol for invasive species

Frontiers in Bioengineering and Biotechnology 8 (452)


Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD’s Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries.


Lumpy skin disease virus (LSDV), is a vector-transmitted poxvirus that causes disease in cattle. The vector species involved in LSDV transmission and their ability to acquire and transmit the virus are poorly characterised. Using a highly representative bovine experimental model of lumpy skin disease we fed four model vector species (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus) on LSDV-inoculated cattle in order to examine the acquisition and retention of LSDV by these species. We found the probability of LSDV transmission from clinical cattle to vector correlated with disease severity. Subclinical disease was more common than clinical disease in the inoculated cattle, however the probability of vectors acquiring LSDV from subclinical animals was very low.

All four potential vector species studied had a similar rate of acquisition of LSDV after feeding on the host, but Aedes aegypti and Stomoxys calcitrans retained the virus for a longer time, up to 8 days. There was no evidence of virus replication in the vector, consistent with mechanical rather than biological transmission. The parameters obtained in this study were combined with data from previously published studies of LSDV transmission and vector life history parameters to determine the basic reproduction number of LSDV in cattle mediated by each of the model species. This was highest for Stomoxys calcitrans (19.1), C. nubeculosus (7.4), and Ae. aegypti (2.4), indicating these three species are potentially efficient transmitters of LSDV, which can be used to inform LSD control programmes.

Importance: Lumpy skin disease virus (LSDV) causes a severe systemic disease characterised by cutaneous nodules in cattle. LSDV is a rapidly emerging pathogen, having spread since 2012 from Africa and the Middle East into Europe, Russia, and across Asia. The vector-borne nature of LSDV transmission is believed to have promoted the rapid geographic spread of the virus, however a lack of quantitative evidence about LSDV transmission has hampered effective control of the disease during the current epidemic. Our research has combined experimental and modelling approaches in order to calculate the reproductive number of different insect species, therefore identifying efficient transmitters of LSDV. It has also characterised a subclinical form of LSDV in cattle and shown that these animals play little part in virus transmission. This information can be used to devise evidence-based, proportionate, and effective control programmes for LSD.


A vaccine providing both powerful antibody and cross-reactive T cell immune responses against influenza viruses would be beneficial for both humans and pigs. Here we evaluated intramuscular (IM), aerosol (Aer) and simultaneous immunization (SIM) by both routes in pigs, using the single cycle candidate influenza vaccine S-FLU. After prime and boost immunization pigs were challenged with H1N1pdm09 virus. IM immunized pigs generated high titer of neutralizing antibodies but poor T cell responses, while Aer induced powerful respiratory tract T cell responses, but a low titer of antibodies. SIM pigs combined high antibody titers and strong local T cell responses. SIM pigs showed the most complete suppression of virus shedding and the greatest improvement in pathology. We conclude that SIM regimes for immunization against respiratory pathogens warrant further study.Competing Interest StatementAT is named on a patent concerning the use of S-FLU as a vaccine. RM is employed by Aerogen Limited, focused on development of vibrating mesh nebulizer technologies. The other authors have no financial conflicts of interest.


Trypanosomes have long been recognised as being amongst the most important protozoan parasites of verte-brates, from both medical and veterinary perspectives. Whilst numerous insect species have been identified as vectors, the role of ticks is less well understood. Here we report the isolation and partial molecular character-isation of a novel trypanosome from questing Ixodes ricinus ticks collected in Slovakia. The trypanosome was isolated in tick cell culture and then partially characterised by microscopy and amplification of fragments of the 18S rRNA and 24S alpha rDNA genes. Analysis of the resultant sequences suggests that the trypanosome designated as Trypanosoma sp. Bratislava1 may be a new species closely related to several species or strains of trypanosomes isolated from, or detected in, ticks in South America and Asia, and to Trypanosoma caninum isolated from dogs in Brazil. This study highlights the potential involvement of ixodid ticks in the epidemiology of trypanosomes, as well as the use of tick cell lines for isolation of such tick-borne protozoa. Further studies are required to in-vestigate the epidemiology, transmission and life cycle of this putative novel species.


Reticuloendotheliosis virus (REV) is an avian retrovirus that causes an oncogenic, immunosuppressive, and runting-stunting syndrome in avian hosts. The co-infection of REV and Marek's disease virus (MDV), an oncogenic herpesvirus in chickens, further increases disease severity and reduces MDV vaccine efficacy. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has successfully been used against pathogens in mammalian cells. However, the large size of the CRISPR-Cas9 coding sequences makes its in vivo delivery challenging. Here, following the design of a panel of single-guided RNAs targeting REV, we demonstrate that CRISPR/Cas9 can efficiently mediate the editing of the long terminal repeats of REV, resulting in the inhibition of viral protein expression. The CRISPR-Cas9 system disrupts the integrated proviral genome and provides defense against new viral infection and replication in chicken cells. Moreover, by constructing recombinant MDV carrying CRISPR-Cas9 components using an attenuated MDV vaccine strain as the vector, we efficiently delivered the CRISPR-Cas9 system into chickens, and the MDV-delivered CRISPR-Cas9 drastically reduced REV viral load and significantly diminished REV-associated symptoms. To our knowledge, this is the first study establishing avian retrovirus resistance in chickens utilizing herpesvirus-delivered CRISPR-Cas9, which provides a novel and effective strategy against viral infections.

Lello L S, Utt A, Bartholomeeusen K, Wang S, Rausalu K, Kendall C, Coppens S, Fragkoudis R, Tuplin A, Alphey L, Ariën K K, Merits A (2020)

Cross-utilisation of template RNAs by alphavirus replicases

PLOS Pathogens 16 (9), e1008825


Alphaviruses are positive-strand RNA viruses, most of which use mosquitoes to spread between vertebrate hosts; many are human pathogens with potentially severe medical consequences. Some alphavirus species are believed to have resulted from the recombination between different members of the genus and there is evidence of movement of alphaviruses between continents. Here, a novel assay uncoupling viral replicase and template RNA production was developed and used to analyse cross-utilization of alphavirus template RNAs. We observed that replicases of closely related alphaviruses belonging to the Semliki Forest virus complex can generally use each other’s template RNAs as well as those of distantly related outgroup viruses. In contrast, replicases of outgroup viruses clearly preferred homologous template RNAs. These trends were observed in both mammalian and mosquito cells, with template preferences generally more pronounced in mosquito cells. Interestingly, the template RNA of the mosquito-specific Eilat virus was efficiently used by other alphavirus replicases while Eilat replicase could not use heterologous templates. Determinants for template selectivity were mapped to the beginning of the RNA genome and template recognition was more likely based on the recognition of RNA sequences than recognition of structural elements formed by the RNAs.

Leftwich P T, Edgington M P, Chapman T (2020)

Transmission efficiency drives host–microbe associations

Proceedings of the Royal Society B: Biological Sciences 287 (1934), 20200820


Sequencing technologies have fuelled a rapid rise in descriptions of microbial communities associated with hosts, but what is often harder to ascertain is the evolutionary significance of these symbioses. Here, we review the role of vertical (VT), horizontal (HT), environmental acquisition and mixed modes of transmission (MMT), in the establishment of animal host–microbe associations. We then model four properties of gut microbiota proposed as key to promoting animal host–microbe relationships: modes of transmission, host reproductive mode, host mate choice and host fitness. We found that: (i) MMT led to the highest frequencies of host–microbe associations, and that some environmental acquisition or HT of microbes was required for persistent associations to form unless VT was perfect; (ii) host reproductive mode (sexual versus asexual) and host mate choice (for microbe carriers versus non-carriers) had little impact on the establishment of host–microbe associations; (iii) host mate choice did not itself lead to reproductive isolation, but could reinforce it; and (iv) changes in host fitness due to host–microbe associations had a minimal impact upon the formation of co-associations. When we introduced a second population, into which host–microbe carriers could disperse but in which environmental acquisition did not occur, highly efficient VT was required for host–microbe co-associations to persist. Our study reveals that transmission mode is of key importance in establishing host–microbe associations


Viruses routinely employ strategies to prevent the activation of innate immune signalling in infected cells. RSV is no exception, encoding two accessory proteins (NS1 and NS2) which are well established to block Interferon signalling. However, RSV-encoded mechanisms for inhibiting NF-κB signalling are less well characterised. In this study we identified RSV-mediated antagonism of this pathway, independent of the NS1 and NS2 proteins, and indeed distinct from other known viral mechanisms of NF-κB inhibition. In both human and bovine RSV infected cells we demonstrated that the P65 subunit of NF-κB is rerouted to perinuclear puncta in the cytoplasm, puncta which are synonymous with viral inclusion bodies (IBs), the site for viral RNA replication. Captured P65 was unable to translocate to the nucleus or transactivate a NF-κB reporter following TNF-α stimulation, confirming the immune-antagonistic nature of this sequestration. Subsequently, we used correlative light electron microscopy (CLEM) to colocalise RSV N protein and P65 within bRSV IBs; granular, membraneless regions of cytoplasm with liquid organelle-like properties. Additional characterisation of bRSV IBs indicated that although they are likely formed by liquid-liquid phase separation (LLPS), they have a differential sensitivity to hypotonic shock proportional to their size. Together, these data identify a novel mechanism for viral antagonism of innate immune signalling which relies on sequestration of the NF-κB subunit p65 to a biomolecular condensate – a mechanism conserved across the Orthopneumovirus genus and not host-cell specific. More generally they provide additional evidence that RNA virus IBs are important immunomodulatory complexes within infected cells.

Importance: Many viruses replicate almost entirely in the cytoplasm of infected cells; however, how these pathogens are able to compartmentalise their life cycle to provide favourable conditions for replication and to avoid the litany of antiviral detection mechanisms in the cytoplasm remains relatively uncharacterised. In this paper we show that bovine RSV (bRSV), which infects cattle, does this by generating inclusion bodies in the cytoplasm of infected cells. We confirm that both bRSV and human RSV viral RNA replication takes place in these inclusion bodies, likely meaning these organelles are a functionally conserved feature of this group of viruses (the orthopneumoviruses). Importantly, we also showed that these organelles are able to capture important innate immune transcription factors (in this case NF-KB), blocking the normal signalling processes that tell the nucleus the cell is infected, which may help us to understand how these viruses cause disease.


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