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

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Zhou J, Zhao G-L, Wang X-M, Du X-S, Su S, Li C-G, Nair V, Yao Y-X, Cheng Z-Q (2018)

Synergistic viral replication of Marek's disease virus and avian leukosis virus subgroup J is responsible for the enhanced pathogenicity in the superinfection of chickens

Viruses 10 (5), 271
Publisher’s version:


Superinfection of Marek's disease virus (MDV) and avian leukosis virus subgroup J (ALV-J) causes lethal neoplasia and death in chickens. However, whether there is synergism between the two viruses in viral replication and pathogenicity has remained elusive. In this study, we found that the superinfection of MDV and ALV-J increased the viral replication of the two viruses in RNA and protein level, and synergistically promoted the expression of IL-10, IL-6, and TGF-β in chicken embryo fibroblasts (CEF). Moreover, MDV and ALV-J protein expression in dual-infected cells detected by confocal laser scanning microscope appeared earlier in the cytoplasm and the nucleus, and caused more severe cytopathy than single infection, suggesting that synergistically increased MDV and ALV-J viral-protein biosynthesis is responsible for the severe cytopathy. In vivo, compared to the single virus infected chickens, the mortality and tumor formation rates increased significantly in MDV and ALV-J dual-infected chickens. Viral loads of MDV and ALV-J in tissues of dual-infected chickens were significantly higher than those of single-infected chickens. Histopathology observation showed that more severe inflammation and tumor cells metastases were present in dual-infected chickens. In the present study, we concluded that synergistic viral replication of MDV and ALV-J is responsible for the enhanced pathogenicity in superinfection of chickens.

Zhang Y, Tang N, Sadigh Y, Baigent S, Shen Z, Nair V, Yao Y (2018)

Application of CRISPR/Cas9 gene editing system on MDV-1 genome for the study of gene function

Viruses 10 (6), 279


Marek's disease virus (MDV) is a member of alphaherpesviruses associated with Marek's disease, a highly contagious neoplastic disease in chickens. Complete sequencing of the viral genome and recombineering techniques using infectious bacterial artificial chromosome (BAC) clones of Marek's disease virus genome have identified major genes that are associated with pathogenicity. Recent advances in CRISPR/Cas9-based gene editing have given opportunities for precise editing of the viral genome for identifying pathogenic determinants. Here we describe the application of CRISPR/Cas9 gene editing approaches to delete the Meq and pp38 genes from the CVI988 vaccine strain of MDV. This powerful technology will speed up the MDV gene function studies significantly, leading to a better understanding of the molecular mechanisms of MDV pathogenesis.

Wilson A J, Harrup L E (2018)

Reproducibility and relevance in insect-arbovirus infection studies

Current Opinion in Insect Science early view,


Experimental infections of insects with arboviruses are performed to achieve a variety of objectives but principally to draw inferences about the potential role of field populations in transmission or to explore the molecular basis of vector–pathogen interactions. The design of such studies determines both their reproducibility and the extent to which their results can be extrapolated to natural environments, and is constrained by the resources available. We discuss recent findings regarding the effects of nutrition, the microbiome, co-infecting agents and feeding methods on the outcome of such experiments, and identify resource-efficient ways to increase their relevance and reproducibility, including the development of community standards for reporting such studies and better standards for cell line and colony authentication.

Sadigh Y, Powers C, Spiro S, Pedrera M, Broadbent A, Nair V (2018)

Gallid herpesvirus 3 SB-1 strain as a recombinant viral vector for poultry vaccination

npj Vaccines 3 (1), 21


Live herpesvirus-vectored vaccines are widely used in veterinary medicine to protect against many infectious diseases. In poultry, three strains of herpesvirus vaccines are used against Marek's disease (MD). However, of these, only the herpesvirus of turkeys (HVT) has been successfully developed and used as a recombinant vaccine vector to induce protection against other avian viral diseases such as infectious bursal disease (IBD), Newcastle disease (ND) or avian influenza (AI). Although effective when administered individually, recombinant HVT vectors have limitations when combined in multivalent vaccines. Thus there is a need for developing additional viral vectors that could be combined with HVT in inducing protection against multiple avian diseases in multivalent vaccines. Gallid herpesvirus 3 (GaHV3) strain SB-1 is widely used by the poultry industry as bivalent vaccine in combination with HVT to exploit synergistic effects against MD. Here, we report the development and application of SB-1 as a vaccine vector to express the VP2 capsid antigen of IBD virus. A VP2 expression cassette was introduced into the SB-1 genome at three intergenic locations (UL3/UL4, UL10/UL11 and UL21/UL22) using recombineering methods on the full-length pSB-1 infectious clone of the virus. We show that the recombinant SB-1 vectors expressing VP2 induced neutralising antibody responses at levels comparable to that of commercial HVT-based VAXXITEKHVT+IBD vaccine. Birds vaccinated with the experimental recombinant SB-1 vaccine were protected against clinical disease after challenge with the very virulent UK661 IBDV isolate, demonstrating its value as an efficient viral vector for developing multivalent vaccines against avian diseases.

Clarke B D, Islam M R, Yusuf M A, Mahapatra M, Parida S (2018)

Molecular detection, isolation and characterization of peste-des-petits ruminants virus from goat milk from outbreaks in Bangladesh and its implication for eradication strategy

Transboundary and Emerging Diseases early view,


Peste-des-petits ruminants (PPR) is a highly contagious transboundary viral disease of small ruminants, which is endemic in much of Africa, the Middle East and Asia. In South Asia, PPR is of significant concern to the Indian subcontinent including Bangladesh as more than 30% of the world's sheep and goats are farmed in this region, predominantly by small, poor and marginal farmers. PPR virus was detected and isolated from goat milk from field samples from PPR outbreaks (2012-2015) in Bangladesh and its full-length sequences obtained. Sequence analysis of the partial N gene of Bangladesh isolates showed 99.3%-100% identity whereas 98.2%-99.6% identity was observed when compared with neighbouring Indian viruses. Further analysis of the full-length genomes indicated that the Bangladesh isolates were 99.3%-99.99% identical among themselves and 98.3%-98.4% identical to neighbouring Indian viruses. These findings further support the transboundary transmission of PPR virus across the Indian and Bangladesh border. In additional, the establishment of a cross-border strategy between India and Bangladesh will be of paramount importance for the eradication of PPR in this region. Molecular detection and isolation of PPR virus from milk is of significant potential concern for spread of the disease to free areas as the major producers of goat milk globally are PPR endemic countries in particular India and Bangladesh, as well as Sudan. Milk is a noninvasive sample type and bulk goat milk sampling for the detection of PPRV would be of practical significance for regional surveillance of PPRV as progress is made towards the targeted 2030 eradication.

Bachanek-Bankowska K, Di Nardo A, Wadsworth J, Henry E K M, Parlak U, Timina A, Mischenko A, Qasim I A, Abdollahi D, Sultana M, Hossain M A, King D P, Knowles N J (2018)

Foot-and-mouth disease in the Middle East caused by an A/ASIA/G-VII virus lineage, 2015-2016

Emerging Infectious Diseases 24 (6), 1073-1078


Phylogenetic analyses of foot-and-mouth disease type A viruses in the Middle East during 2015-2016 identified viruses belonging to the A/ASIA/G-VII lineage, which originated in the Indian subcontinent. Changes in a critical antigenic site within capsid viral protein 1 suggest possible evolutionary pressure caused by an intensive vaccination program.

Metcalfe H J, Biffar L, Steinbach S, Guzman E, Connelley T, Morrison I, Vordermeier H M, Villarreal-Ramos B (2018)

Ag85A-specific CD4(+) T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties

Vaccine 36 (20), 2850-2854


There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4+ T cells post-boosting. Here, the capacity of Ag85A-specific CD4+ T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4+ T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1beta, IL-12, IFNgamma or TNFalpha) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4+ T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology.

Lasecka-Dykes L, Wright C F, Di Nardo A, Logan G, Mioulet V, Jackson T, Tuthill T J, Knowles N J, King D P (2018)

Full genome sequencing reveals new Southern African Territories genotypes bringing us closer to understanding true variability of foot-and-mouth disease virus in Africa

Viruses 10 (4), 192


Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hooved animals that poses a constant burden on farmers in endemic regions and threatens the livestock industries in disease-free countries. Despite the increased number of publicly available whole genome sequences, FMDV data are biased by the opportunistic nature of sampling. Since whole genomic sequences of Southern African Territories (SAT) are particularly underrepresented, this study sequenced 34 isolates from eastern and southern Africa. Phylogenetic analyses revealed two novel genotypes (that comprised 8/34 of these SAT isolates) which contained unusual 5′ untranslated and non-structural encoding regions. While recombination has occurred between these sequences, phylogeny violation analyses indicated that the high degree of sequence diversity for the novel SAT genotypes has not solely arisen from recombination events. Based on estimates of the timing of ancestral divergence, these data are interpreted as being representative of un-sampled FMDV isolates that have been subjected to geographical isolation within Africa by the effects of the Great African Rinderpest Pandemic (1887–1897), which caused a mass die-out of FMDV-susceptible hosts. These findings demonstrate that further sequencing of African FMDV isolates is likely to reveal more unusual genotypes and will allow for better understanding of natural variability and evolution of FMDV.

Yao Y, Zhang Y, Tang N, Pedrera M, Shen Z, Nair V (2018)

Inhibition of v-rel-Induced oncogenesis through microRNA targeting

Viruses 10 (5),
Publisher’s version:


Several studies have shown that microRNA-targeting is an effective strategy for the selective control of tissue-tropism and pathogenesis of both DNA and RNA viruses. However, the exploitation of microRNA-targeting for the inhibition of transformation by oncogenic viruses has not been studied. The v-rel oncoprotein encoded by reticuloendotheliosis virus T strain (Rev-T) is a member of the rel/NF-κB family of transcription factors capable of transforming primary chicken spleen and bone marrow cells. Here, by engineering the target sequence of endogenous microRNA miR-142 downstream of the v-rel gene in a Replication-Competent ALV (avian leukosis virus) long terminal repeat (LTR) with a splice acceptor (RCAS) vector and using a v-rel-induced transformation model of chicken embryonic splenocyte cultures, we show that hematopoietic-specific miR-142 can inhibit the v-rel-induced transformation, and that this inhibition effect is due to the silencing of v-rel expression. The data supports the idea that microRNA-targeting can be used to inhibit viral oncogene-induced oncogenesis.

Tungatt K, Dolton G, Morgan S B, Attaf M, Fuller A, Whalley T, Hemmink J D, Porter E, Szomolay B, Montoya M, Hammond J A, Miles J J, Cole D K, Townsend A, Bailey M, Rizkallah P J, Charleston B, Tchilian E, Sewell A K (2018)

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig

PLoS Pathogens 14 (5), e1007017


There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens.


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