Publications

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

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Abstract

The housing of animals at night was investigated as a possible means of protecting them from attack by Culicoides biting midges (Diptera: Ceratopogonidae), the vectors of bluetongue. Light-trap catches of Culicoides were compared inside and outside animal housing, in the presence and absence of cattle. A three-replicate, 4 × 4 Latin square design was used at four farms in Bala, north Wales, over 12 nights in May and June 2007, and the experiment repeated in October. In the two studies, respectively, >70 000 and >4500 Culicoides were trapped, of which 93% and 86%, respectively, were of the Culicoides obsoletus group. Across the four farms, in May and June, the presence of cattle increased catches of C. obsoletus by 2.3 times, and outside traps caught 6.5 times more insects than inside traps. Similar patterns were apparent in October, but the difference between inside and outside catches was reduced. Catches were strongly correlated with minimum temperature and maximum wind speed and these two variables explained a large amount of night-to-night variation in catch. Outside catches were reduced, to a greater extent than inside catches, by colder minimum temperatures and higher maximum wind speeds. These conditions occur more frequently in October than in May and June, thereby suppressing outside catches more than inside catches, and reducing the apparent degree of exophily of C. obsoletus in autumn. The results suggest that the risk of animals receiving bites from C. obsoletus is reduced by housing at both times of year and the benefit would be greatest on warm, still nights when outside catches are at their greatest.
Beard P M, Sugar S, Bazarragchaa E, Gerelmaa U, Tserendorj S, Tuppurainen E, Sodnomdarjaa R (2010)

A description of two outbreaks of capripoxvirus disease in Mongolia

Veterinary Microbiology 142 (3-4), 427-431

Abstract

Mongolia had no reported cases of capripoxvirus disease from 1977 until an outbreak of sheeppox in 2006–/2007 and then goatpox in 2008. The two outbreaks occurred in geographically distant areas of Mongolia and, most strikingly, were highly species-specific. The 2006–/2007 sheeppox outbreak affected no goats and the 2008 goatpox outbreak affected no sheep despite communal herding. The diseases were diagnosed using the polymerase chain reaction and virus neutralisation test. The P32 gene of the Mongolian sheeppox and goatpox viruses from the recent outbreaks were sequenced and compared with an archived 1967 strain of Goatpox virus from Mongolia. The P32 gene of the 2006/–2007 Mongolian Sheeppox virus strain was identical to previously published sheeppox strains. The P32 gene of the 2008 Mongolian Goatpox virus strain was identical to the gene from virus isolated from recent goatpox outbreaks in China and Vietnam. The archived Mongolian Goatpox virus strain was unique.

Abstract

Chlamydophila (Cp.) psittaci and avian pathogenic Escherichia (E.) coli infections contribute to the respiratory disease complex observed in turkeys. Secondary infection with E. coli exacerbates Cp. psittaci pathogenicity and augments E. coli excretion. The innate immune response initiated by both pathogens in their avian host is unknown. We therefore determined the cytokine responses following Cp. psittaci infection and E. coli superinfection of avian monocytes/macrophages by examining gene transcripts of IL-1?, IL-6, CXCLi2 (IL-8), CXCLi1 (K60), IL-10, IL-12?/?, IL-18, TGF-?4 and CCLi2 at 4 h post-inoculation with different Cp. psittaci strains or 4 h post-treatment with avian E. coli LPS of Cp. psittaci pre-infected HD11 cells. Cp. psittaci strains used were 84/55 and 92/1293 (highly virulent), CP3 (low virulent) and 84/2334 (phylogenetically intermediate between Cp. psittaci and Chlamydophila abortus). At 4 h post chlamydial infection, an increased expression of IL-1? and IL-6 as well as CXCLi2, CXCLi1 and CCLi2 was observed compared to levels in uninfected HD11 controls. This effect was less pronounced for the milder CP3 strain. The pro-inflammatory response of Cp. psittaci infected cells to E. coli LPS was significantly lowered compared to uninfected controls, especially when the cells were pre-infected with highly virulent Cp. psittaci strains. In both experiments, exceptionally high IL-10 and no TGF-?4 responses were observed, and we propose that this could induce macrophage deactivation and NF-?B suppression. Consequently, pro-inflammatory and Th1-promoting responses to both the primary Cp. psittaci infection and E. coli would be inhibited, thus explaining the observed aggravated in vivo pathology.

Abstract

BACKGROUND: alpha-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients. METHODS: We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-gamma. RESULTS: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P = 0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child-Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child-Pugh A score and in 46% with a B or C score. CONCLUSION: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.

Abstract

Cell-mediated immune responses play an important role in the control of tumour growth. CD4 and CD8 T cells recognise tumour antigens presented via major histocompatibility complex molecules of antigen presenting cells and develop into effector cells with the ability to identify and kill tumour cells. Here, we re-examine the adaptive immune response to tumour antigens expressed by hepatocellular carcinoma (HCC) and discuss approaches that could be applied in future T-cell-based immunotherapy schedules to induce a potent and effective antitumour immunity. Moreover, we discuss cytotoxic T lymphocyte and Th1 responses to tumour antigens in patients with HCC and evaluate the effects of conventional treatments on antitumour T-cell responses.

Abstract

The presence of CD8 T cell responses to tumor associated antigens have been reported in patients with different malignancies. However, there is very little information on a comparable CD8 and CD4 T cell response to a tumor antigen in liver cancer patients. Here, we re-examine the kinetic and the pattern of T helper 1 and cytotoxic T lymphocyte responses to alpha-fetoprotein (AFP), a tumor rejection antigen in hepatocellular carcinoma (HCC). Then, we discuss the possibility of using AFP-based immunotherapy in combination with necrotizing treatments in HCC patients.
Sen A, Saravanan P, Balamurugan V, Rajak K K, Sudhakar S B, Bhanuprakash V, Parida S, Singh R K (2010)

Vaccines against peste des petits ruminants virus

Expert Review of Vaccines 9 (7), 785-796

Abstract

Peste des petits ruminants (PPR) is a highly contagious and economically important viral disease affecting goats, sheep and wild ruminants. The disease is currently circulating in Asian and African countries, creating problems in small ruminant farming. Current control of the disease mainly includes isolation and disinfection of the contaminated environment, and administration of a live-attenuated vaccine, which provides a strong immunity. Maintenance of cold chain for vaccine efficacy has proven difficult in subtropical countries. A thermostable live-attenuated conventional or recombinant vaccine is a way to avoid cold chain-associated problems in tropical and subtropical countries. Mass vaccination of sheep and goats in endemic countries might be a pragmatic approach to control PPR in the first phase of disease eradication. In the future, the development of a marker vaccine with a robust companion test may help in serosurveillance to identify infection in vaccinated animals to control PPR disease. Here, we discuss available potent PPR vaccines and the future possibility of developing new-generation vaccines against PPR.
O'Donoghue N, Sweeney T, Donagh R, Clarke K J, Porter R K (2009)

Control of choline oxidation in rat kidney mitochondria

Biochimica et Biophysica Acta 1787 (9), 1135-11359

Abstract

Choline is a quaternary amino cationic organic alcohol that is oxidized to betaine in liver and kidney mitochondria. Betaine acts as an intracellular organic osmolyte in the medulla of the kidney. Evidence is provided that kidney mitochondria have a choline transporter in their inner membrane. The transporter has a Km of 173 ± 64 μM and a Vmax of 0.4 ± 0.1 nmol/min/mg mitochondrial protein (at 10 °C). Uptake of choline is not coupled to betaine efflux. Transporter activity demonstrates a dependence on membrane potential and choline transport is inhibited by hemicholinium-3. Steady-state oxygen consumption due to choline oxidation in kidney mitochondria was measurable at 37 °C (125 ± 6 pmolO2/min/mg mitochondrial protein), in the absence of other mitochondrial electron transport chain substrates and the choline transporter was shown to be the major site of control (96 ± 4%) over choline oxidation flux in isolated kidney mitochondria. We conclude that the choline transporter in rat kidney mitochondria is the major site of control over the production of the organic osmolyte, betaine.

Abstract

The mechanism by which herpesviruses acquire their tegument is not yet clear. One model is that outer tegument proteins are recruited by the cytoplasmic tails of viral glycoproteins. In the case of herpes simplex virus tegument protein VP22, interactions with the glycoproteins gE and gD have been shown. We have previously shown that the C-terminal half of VP22 contains the necessary signal for assembly into the virus. Here, we show that during infection VP22 interacts with gE and gM, as well as its tegument partner VP16. However, by using a range of techniques we were unable to demonstrate VP22 binding to gD. By using pulldown assays, we show that while the cytoplasmic tails of both gE and gM interact with VP22, only gE interacts efficiently with the C-terminal packaging domain of VP22. Furthermore, gE but not gM can recruit VP22 to the Golgi/trans-Golgi network region of the cell in the absence of other virus proteins. To examine the role of the gE-VP22 interaction in infection, we constructed a recombinant virus expressing a mutant VP22 protein with a 14-residue deletion that is unable to bind gE (ΔgEbind). Coimmunoprecipitation assays confirmed that this variant of VP22 was unable to complex with gE. Moreover, VP22 was no longer recruited to its characteristic cytoplasmic trafficking complexes but exhibited a diffuse localization. Importantly, packaging of this variant into virions was abrogated. The mutant virus exhibited poor growth in epithelial cells, similar to the defect we have observed for a VP22 knockout virus. These results suggest that deletion of just 14 residues from the VP22 protein is sufficient to inhibit binding to gE and hence recruitment to the viral envelope and assembly into the virus, resulting in a growth phenotype equivalent to that produced by deleting the entire reading frame.

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