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

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Zou H, Su R, Ruan J, Shao H, Qian K, Ye J, Yao Y, Nair V, Qin A (2017)

Double-stranded RNA induces chicken T-cell lymphoma apoptosis by TRIF and NF-κB

Scientific Reports 7 (1), 7547


Toll-like receptor-3 (TLR3), a member of the pathogen recognition receptor family, has been reported to activate immune response and to exhibit pro-apoptotic activity against some tumor cells. However it is unclear whether TLR3 has same function against chicken lymphoma. In this paper we investigated the effect of TLR3 activation on a Marek’s disease lymphoma-derived chicken cell line, MDCC-MSB1. The TLR3 agonist poly (I:C) activated TLR3 pathway and inhibited tumor cells proliferation through caspase-dependent apoptosis. Using pharmacological approaches, we found that an interferon-independent mechanism involving Toll-IL-1-receptor domain-containing adapter-inducing IFN-α (TRIF) and nuclear factor κB (NF-κB) causes the apoptosis of MDCC-MSB1 cells. This is the first report about the function of TLR3 in chicken T-cell lymphoma, especially in signal pathway. The mechanisms underlying TLR3-mediated apoptosis may contribute to the development of new drug to treat lymphomas and oncovirus infections.

Hoa L N M, Tuan N A, My P H, Huong T T K, Chi N T Y, Hau Thu T T, Carrique-Mas J, Duong M T, Tho N D, Hoang N D, Thanh T L, Diep N T, Duong N V, Toan T K, Tung T S, Mai L Q, Iqbal M, Wertheim H, van Doorn H R, Bryant J E, The Vizions C (2017)

Assessing evidence for avian-to-human transmission of influenza A/H9N2 virus in rural farming communities in northern Vietnam

Journal of General Virology early view,


Rural farming communities in northern Vietnam do not routinely practice vaccination for influenza A viruses (IAV) for either humans or poultry, which enables us to study transmission intensity via seroepidemiology. Using samples from a longitudinal cohort of farming households, we determined the number of symptomatic and asymptomatic human infections for seasonal IAV and avian A/H9 over 2 years. As expected, we detected virologically confirmed acute cases of seasonal IAV in humans, as well as large numbers of subclinical seroconversions to A/H1pdm [55/265 (21 %)], A/H3 [95/265 (36 %)] and A/H9 [24/265 (9 %)]. Five of the A/H9 human seroconverters likely represented true infections rather than heterosubtypic immunity, because the individuals seroconverted solely to A/H9. Among co-located poultry, we found significantly higher seroprevalance for A/H5 compared to A/H9 in both chickens and ducks [for northern study sites overall, 337/1105 (30.5 %) seropositive for A/H5 and 123/1105 (11.1 %) seropositive for A/H9].

Bande F, Arshad S S, Omar A R, Hair-Bejo M, Mahmuda A, Nair V (2017)

Global distributions and strain diversity of avian infectious bronchitis virus: a review

Animal Health Research Reviews 18 (1), 70-83


The poultry industry faces challenge amidst global food security crisis. Infectious bronchitis is one of the most important viral infections that cause huge economic loss to the poultry industry worldwide. The causative agent, infectious bronchitis virus (IBV) is an RNA virus with great ability for mutation and recombination; thus, capable of generating new virus strains that are difficult to control. There are many IBV strains found worldwide, including the Massachusetts, 4/91, D274, and QX-like strains that can be grouped under the classic or variant serotypes. Currently, information on the epidemiology, strain diversity, and global distribution of IBV has not been comprehensively reported. This review is an update of current knowledge on the distribution, genetic relationship, and diversity of the IBV strains found worldwide.

Rehman Z U, Meng C, Umar S, Mahrose K M, Ding C, Munir M (2017)

Mast cells and innate immunity: master troupes of the avian immune system

World's Poultry Science Journal 73 (3), 621-632


Mast cells (MCs) are granulated cells of haematopoietic lineage and constitute a major sensory arm of the immune system. MCs dually guard hosts and regulate immune responses against invading pathogens. This property of the MCs is attributed to their adaptability to detect stress signals and pathogens, and the production of signal specific mediators to engage immune cells for clearance of infectious agents. Pathogen-specific signals establish basis for the initiation of adoptive immune responses. These immune regulatory roles of MCs have opened avenues to engage different MCs activators which culminate in effective passive immunisation. The molecular mechanisms and dynamics of functionalities of MCs in host defences have been extensively characterised in mammals and rodents, and research on MCs in avian species is emerging. This review surveys the development, morphology and distribution of MCs in different tissues of the poultry and highlight areas that can be exploited for disease control and prevention.

Belova O A, Litov A G, Kholodilov I S, Kozlovskaya L I, Bell-Sakyi L, Romanova L I, Karganova G G (2017)

Properties of the tick-borne encephalitis virus population during persistent infection of ixodid ticks and tick cell lines

Ticks and Tick-borne Diseases 8 (6), 895-906


Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis (TBE), a vector-borne zoonotic neuroinfection. For successful circulation in natural foci the virus has to survive in the vector for a long period of time. Information about the effect of long-term infection of ticks on properties of the viral population is of great importance. In recent years, changes in the eco-epidemiology of TBEV due to changes in distribution of ixodid ticks have been observed. These changes in TBEV-endemic areas could result in a shift of the main tick vector species, which in turn may lead to changes in properties of the virus. In the present study we evaluated the selective pressure on the TBEV population during persistent infection of various species of ticks and tick cell lines. TBEV effectively replicated and formed persistent infection in ticks and tick cell lines of the vector species (Ixodes spp.), potential vectors (Dermacentor spp.) and non-vector ticks (Hyalomma spp.). During TBEV persistence in Ixodes and Dermacentor ticks, properties of the viral population remained virtually unchanged. In contrast, persistent TBEV infection of tick cell lines from both vector and non-vector ticks favoured selection of viral variants with low neuroinvasiveness for laboratory mice and substitutions in the E protein that increased local positive charge of the virion. Thus, selective pressure on viral population may differ in ticks and tick cell lines during persistent infection. Nevertheless, virus variants with properties of the original strain adapted to mouse CNS were not eliminated from the viral population during long-term persistence of TBEV in ticks and tick cell lines.

Chen Y, Xue S A, Behboudi S, Mohammad G H, Pereira S P, Morris E (2017)

Ex vivo PD-L1/PD-1 pathway blockade reverses dysfunction of circulating CEA specific T cells in pancreatic cancer patients

Clinical Cancer Research 23 (20), 6178-6189


Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer (PC). In this study, we have characterised the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2 restricted peptide, pCEA691-699, isolated from the peripheral T cell repertoire of PC patients and sought to determine if ex vivo PD-L1 & TIM3 blockade could enhance CTL function. CD8+ T cell lines were generated from peripheral blood mononuclear cells (PBMCs) of 18 HLA-A2+ patients with PC and from 15 healthy controls. In vitro peptide specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and CSFE cytotoxicity assays using pancreatic cancer cell lines as targets. Cytokine secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18 PC patients, with two CTL lines able to recognise and kill both CEA691 peptide-loaded T2 cells and CEA+ HLA-A2+ pancreatic cancer cell lines. In the presence of ex vivo PD-L1 blockade, functional CEA691-specific CD8+ T cell responses, including IFN-g secretion and proliferation, were enhanced and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes. These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T cell repertoire of PC patients and that their function can be enhanced by PD-L1 blockade.

Edgington M P, Alphey L S (2017)

Conditions for success of engineered underdominance gene drive systems

Journal of Theoretical Biology 430, 128-140


Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens.

Ansari-Lari M, Mohebbi-Fani M, Lyons N A, Azizi N (2017)

Impact of FMD outbreak on milk production and heifers' growth on a dairy herd in southern Iran

Preventive Veterinary Medicine 144, 117-122


Foot and mouth disease is endemic in Middle Eastern countries including Iran but its impact is poorly characterized. The present study was conducted to evaluate the impact of FMD outbreak on milk production and heifers' growth in an industrial dairy herd located in Fars province, southern Iran. Data about individual milk production, heifers' growth and total daily milk (sold for manufacturing), its fat and protein content and somatic cell counts were collected from the herd database. Based on the results of the linear mixed models, a significant decline in individual milk production after the outbreak was observed compared with before the outbreak. There was a total reduction of 8.0 and 4.7% in mean daily milk production per cow after the outbreak when compared with before (over a 42days outbreak period) in lactation one (P<0.001) and lactation >/=2 cows (P=0.024), respectively. The total daily milk (P=0.027) and protein (P=0.002) showed significant decline during the outbreak period. The fat content decreased after the outbreak (P=0.014). Somatic cell counts did not show significant changes. The recorded heifers' weights (4-17 months of age) showed 7.1kg decrease after the outbreak in comparison with the period before that (P<0.001). In conclusion, we observed a negative impact of FMD outbreak on milk production and heifers' growth in study herd. The impact on daily milk production was less than the values reported previously. This difference could be attributed at least partly to differences in livestock genetics and management practices. Lower growth rate of heifers after the outbreak period could potentially extend the age at first calving. It is suggested that farmers are educated on awareness and preparation for infectious disease outbreaks and to practice good management routines that could potentially reduce the economic impact of these diseases.

Pollock N, Taylor G, Jobe F, Guzman E (2017)

Modulation of the transcription factor NF-kappaB in antigen-presenting cells by bovine respiratory syncytial virus small hydrophobic protein

Journal of General Virology 98 (7), 1587-1599


Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease in young cattle and is closely related to human RSV (HRSV), which causes severe respiratory disease in infants and the elderly. The RSV genome encodes a small hydrophobic (SH) protein with viroporin activity. Previous studies have shown that recombinant BRSV lacking the SH gene (rBRSVDeltaSH) is attenuated in the lungs, but not in the upper respiratory tract, of calves and mucosal vaccination with rBRSVDeltaSH induced long-lasting protective immunity. Attenuation of rBRSVDeltaSH may be due to the ability of this virus to induce an early innate response as rBRSVDeltaSH induces higher levels of pro-inflammatory cytokines than wild-type (wt) rBRSV. In this study, we investigated the effects of the BRSV SH protein on NF-kappaB p65 phosphorylation, a master step in the regulation of pro-inflammatory cytokines. Expression of SH resulted in the inhibition of NF-kappaB p65 phosphorylation in response to BRSV infection and extracellular lipopolysaccharide, and a reduction in the production of pro-inflammatory cytokines. In contrast, rBRSVDeltaSH does not inhibit NF-kappaB p65 phosphorylation in bovine antigen-presenting cells, including monocytes, macrophages and dendritic cells, resulting in increased expression of pro-inflammatory cytokines and increased activation of T cells compared to cells infected with wt BRSV. These findings highlight an important role for the BRSV SH protein in immune modulation.


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