Publications

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

There were a total of 1710 results for your search.
Ahmed Mahgoub H, Elnaggar A, Sadeyen J-R (2017)

Implementation of tissue histopathology and parasitic morphometric analysis in the diagnosis of Myxobolus fomenai infection in the skeletal muscles Nile tilapia

American Journal of Infectious Diseases and Microbiology 5 (4), 137-142
Publisher’s version:

Abstract

Class Myxosporea includes Myxobolus parasite. Myxosporean species could infect the skeletal muscles of freshwater fish, including Nile tilapia. In this study, four Nile tilapia fish, collected from a fish farm in Dakahleya province, died and showed gross lesions of haemorrhage on the outer surface (external skeletal muscles and fins). Fish was necropsied and samples were collected for both histopathological examination and quantitative analysis of the transcriptional level of interleukin-8 and tumour necrosis factor-α mRNA in selected tissues. Careful examination revealed the residence of myxospore-producing plasmodia in the affected skeletal muscles of Nile tilapia. The morphometric analysis revealed approximate morphometric results to Myxobolus fomenai. The plasmodia were detected in the skeletal muscles, focally replacing the muscle tissue and containing various developmental stages. The parasite was either surrounded with polymorphnuclear and mononuclear cells and few erythrocytes (haemorrhage), together with necrosis of the adjacent myocytes, or it was seen with sparse or without inflammatory reaction. Transcriptional analysis of interleukin-8 and tumour necrosis factor-α in the skeletal muscles, fins, spleen, and head-kidney revealed the slight down-regulation of interleukin-8 and tumour necrosis factor-α mRNA in the skeletal muscles and their slight up-regulation in the fins of infected fish. However, their mRNA levels in the spleen and head-kidney remained unaffected by infection. Careful future histopathological examination is required to reveal the possibility of Myxobolus fomenai infection in other organs of Nile tilapia. In addition, further immunological investigation needs to be accomplished in relation to such parasitological infestation.

Gurung A, Kamble N, Kaufer B B, Pathan A, Behboudi S (2017)

Association of Marek's disease induced immunosuppression with activation of a novel regulatory T cell

PLOS Pathogens 13 (12), e1006745

Abstract

Marek's Disease Virus (MDV) is an alphaherpesvirus that infects chickens, transforms CD4+ T cells and causes deadly lymphomas. In addition, MDV induces immunosuppression early during infection by inducing cell death of the infected lymphocytes, and potentially due to activation of regulatory T (Treg)-cells. Furthermore, immunosuppression also occurs during the transformation phase of the disease; however, it is still unknown how the disease can suppress immune response prior or after lymphoma formation. Here, we demonstrated that chicken TGF-beta+ Treg cells are found in different lymphoid tissues, with the highest levels found in the gut-associated lymphoid tissue (cecal tonsil: CT), fostering an immune-privileged microenvironment exerted by TGF-beta. Surprisingly, significantly higher frequencies of TGF-beta+ Treg cells are found in the spleens of MDV-susceptible chicken lines compared to the resistant line, suggesting an association between TGF-beta+ Treg cells and host susceptibility to lymphoma formation. Experimental infection with a virulent MDV elevated the levels of TGF-beta+ Treg cells in the lungs as early as 4 days post infection, and during the transformation phase of the disease in the spleens. In contrast to TGF-beta+ Treg cells, the levels of CD4+CD25+ T cells remained unchanged during the infection and transformation phase of the disease. Furthermore, our results demonstrate that the induction of TGF-beta+ Treg cells is associated with pathogenesis of the disease, as the vaccine strain of MDV did not induce TGF-beta+ Treg cells. Similar to human haematopoietic malignant cells, MDV-induced lymphoma cells expressed high levels of TGF-beta but very low levels of TGF-beta receptor I and II genes. The results confirm that COX-2/ PGE2 pathway is involved in immunosuppression induced by MDV-lymphoma cells. Taken together, our results revealed a novel TGF-beta+ Treg subset in chickens that is activated during MDV infection and tumour formation.

Reeman S, Gates A J, Pulford D J, Krieg A, Ulaeto D O (2017)

Protection of mice from lethal vaccinia virus infection by vaccinia virus protein subunits with a CpG Adjuvant

Viruses 9 (12), 378
Publisher’s version: http://dx.doi.org/10.3390/v9120378

Abstract

Smallpox vaccination carries a high risk of adverse events in recipients with a variety of contra-indications for live vaccines. Although alternative non-replicating vaccines have been described in the form of replication-deficient vaccine viruses, DNA vaccines, and subunit vaccines, these are less efficacious than replicating vaccines in animal models. DNA and subunit vaccines in particular have not been shown to give equivalent protection to the traditional replicating smallpox vaccine. We show here that combinations of the orthopoxvirus A27, A33, B5 and L1 proteins give differing levels of protection when administered in different combinations with different adjuvants. In particular, the combination of B5 and A27 proteins adjuvanted with CpG oligodeoxynucleotides (ODN) gives a level of protection in mice that is equivalent to the Lister traditional vaccine in a lethal vaccinia virus challenge model.

Limon G, Fournié G, Lewis E G, Dominguez-Salas P, Leyton-Michovich D, Gonzales-Gustavson E A, Gonzalez A E, Cabezas A H, Pinto J, Rushton J, Guitian J (2017)

Using mixed methods to assess food security and coping strategies: a case study among smallholders in the Andean region

Food Security 9 (5), 1019-1040

Abstract

International organizations and national governments in resource-scarce settings regularly support programs for the control of animal diseases with the aim of improving smallholder food security. However, the impact of such disease control programs on smallholder food security remains unclear. Mixed methods designs that integrate the collection, analysis and interpretation of qualitative and quantitative data in a single study, are increasingly being used to achieve deeper explorations of complex topics. We propose a mixed methods design to assess the four pillars of food security and coping strategies among smallholders. The methodology is illustrated with a case study in the context of a transnational program for the control of Foot and Mouth Disease (FMD) in the Andean region, involving interviews with 632 smallholders in three countries. Quantitative data were analysed using multivariate analysis to describe smallholders’ profiles. Food Consumption Score (FCS) was calculated for each household. The qualitative phase involved developing themes to characterise these smallholders’ experiences using Thematic Analysis. Food acquisition capacity and coping strategies varied greatly across smallholders. Only nine (1.4%) of households had a FCS below the acceptable threshold, however, food stability was compromised across study areas. Household production, financial capacity, household demographics and food prices were the main factors influencing variation in food consumption. The case study presented here illustrates the use of a mixed methods approach to assess the four dimensions of food security and categorise key differences across smallholders during a single visit.

Meng X Y, Luo Y Z, Anwar M N, Sun Y, Gao Y, Zhang H W, Munir M, Qiu H J (2017)

Long non-coding RNAs: emerging and versatile regulators in host-virus interactions

Frontiers in Immunology 8, 1663

Abstract

Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules, which are involved in various biological processes, including chromatin modification, cell differentiation, pre-mRNA transcription and splicing, protein translation, etc. During the last decade, increasing evidence has suggested the involvement of lncRNAs in both immune and antiviral responses as positive or negative regulators. The immunity-associated lncRNAs modulate diverse and multilayered immune checkpoints, including activation or repression of innate immune signaling components, such as interleukin (IL)-8, IL-10, retinoic acid inducible gene I, toll-like receptors 1, 3, and 8, and interferon (IFN) regulatory factor 7, transcriptional regulation of various IFN-stimulated genes, and initiation of the cell apoptosis pathways. Additionally, some virus-encoded lncRNAs facilitate viral replication through individually or synergistically inhibiting the host antiviral responses or regulating multiple steps of the virus life cycle. Moreover, some viruses are reported to hijack host-encoded lncRNAs to establish persistent infections. Based on these amazing discoveries, lncRNAs are an emerging hotspot in host-virus interactions. In this review, we summarized the current findings of the hostor virus-encoded lncRNAs and the underlying mechanisms, discussed their impacts on immune responses and viral replication, and highlighted their critical roles in host-virus interactions.

Hu B, Gonzales J L, Gubbins S (2017)

Bayesian inference of epidemiological parameters from transmission experiments

Scientific Reports 7 (1), 16774

Abstract

Epidemiological parameters for livestock diseases are often inferred from transmission experiments. However, there are several limitations inherent to the design of such experiments that limits the precision of parameter estimates. In particular, infection times and latent periods cannot be directly observed and infectious periods may also be censored. We present a Bayesian framework accounting for these features directly and employ Markov chain Monte Carlo techniques to provide robust inferences and quantify the uncertainty in our estimates. We describe the transmission dynamics using a susceptible-exposed-infectious-removed compartmental model, with gamma-distributed transition times. We then fit the model to published data from transmission experiments for foot-and-mouth disease virus (FMDV) and African swine fever virus (ASFV). Where the previous analyses of these data made various assumptions on the unobserved processes in order to draw inferences, our Bayesian approach includes the unobserved infection times and latent periods and quantifies them along with all other model parameters. Drawing inferences about infection times helps identify who infected whom and can also provide insights into transmission mechanisms. Furthermore, we are able to use our models to measure the difference between the latent periods of inoculated and contact-challenged animals and to quantify the effect vaccination has on transmission.

Gordon S J G, Bolwell C, Rogers C W, Musuka G, Kelly P, Guthrie A, Mellor P S, Hamblin C (2017)

A serosurvey of bluetongue and epizootic haemorrhagic disease in a convenience sample of sheep and cattle herds in Zimbabwe

Onderstepoort Journal of Veterinary Research 84 (1), a1505

Abstract

A convenience sample of sheep and cattle herds around the cities of Harare, Kwekwe and Bulawayo, located in the Highveld region of Zimbabwe, was used to estimate the sero-prevalence and sero-incidence of bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) antibodies. A competitive enzyme-linked immunosorbent assay was used to identify serum antibodies against BTV and EHDV across three rainy seasons. The median sero-prevalence of BTV and EHDV antibodies in cattle was 62% (interquartile range [IQR]: 30-89) and 56% (IQR: 5-77), respectively. In sheep, the median sero-prevalence of BTV and EHDV was 41% (IQR: 19-63) and 0% (IQR: 0-21), respectively. Median sero-incidences of BTV and EHDV antibodies in cattle of 43% (IQR: 22-67) and 27% (IQR: 9-57) respectively were recorded. The median sero-incidence of BTV in sheep was 14% (IQR: 6-23). Based on these preliminary findings, animal health workers in Zimbabwe should continue to monitor the exposure rates of cattle and sheep to BTV and consider the possibility of strains emerging with increased pathogenicity. There are no previous published reports of antibodies against EHDV in Zimbabwe so the possibility of epizootic haemorrhagic disease existing in domestic livestock should now be considered by Zimbabwean animal health officials. Seroconversions to BTV and EHDV occurred predominantly at the end of each rainy season (March and April), which generally corresponds to high numbers of the Culicoides vectors. BTV isolations were made from three individual cows in two of the sentinel herds and all three were identified as serotype 3. This is the first time BTV serotype 3 has been recorded in Zimbabwe, although its presence in neighbouring South Africa is well documented.

Rao P P, Hegde N R, Singh K P, Putty K, Hemadri D, Maan N S, Reddy Y N, Maan S, Mertens P P C (2017)

Bluetongue: Aetiology, Epidemiology, Pathogenesis, Diagnosis and Control (chapter 1)

In: Bayry, J (ed.) Emerging and Re-emerging Infectious Diseases of Livestock, Springer , 3-54

Abstract

Bluetongue (BT) is an emerging and re-emerging vector-borne viral disease of domestic and wild ruminants, caused by viruses classified within the species bluetongue virus (BTV), genus Orbivirus, family Reoviridae. There are 27 recognized serotypes of BTV (with two more recently discovered ‘putative’ serotypes) as well as multiple geographic variants (topotypes) and many different strains and genotypes, most of which are transmitted between their vertebrate hosts by certain ‘vector-competent’ biting midges of the genus Culicoides. Bluetongue is an economically important transboundary disease that is listed by the World Organisation for Animal Health, reflecting the ability of BTV to (a) infect all ruminants, including important domesticated species; (b) cause severe disease, with high fatality rates in sheep and certain species of deer; and (c) cause large economic losses due to fatalities, reduced productivity and reproductive performance, animal movement and trade restrictions and surveillance and control strategies (including vaccination). The plurality of BTV serotypes and strains, the involvement of multiple host and vector species and the potential for (re)introduction of exotic BTV strains make the control and eradication of BT very complex and difficult to achieve. In this chapter, we review the current understanding of BTV biology, bluetongue epidemiology, pathogenesis and pathology, laboratory techniques to diagnose the disease and identify the virus, experimental animal models to study the disease and to evaluate vaccines and methods for the control and/or eradication of bluetongue.

Howson E L A, Soldan A, Webster K, Beer M, Zientara S, Belák S, Sánchez-Vizcaíno J M, Van Borm S, King D P, Fowler V L (2017)

Technological advances in veterinary diagnostics: opportunities to deploy rapid decentralised tests to detect pathogens affecting livestock.

Revue Scientifique et Technique 36 (2), 479-498
Publisher’s version:

Abstract

Sustainable food production capable of feeding a growing human population is a significant global challenge, and is a priority encompassed within the United Nations Millennium Development Goals to ‘eradicate extreme poverty and hunger’. Infectious diseases reduce the productivity of farm animals, and the globalised trade of animals and their products increases the threat of disease incursion. Accurate and rapid diagnostic tests are an essential component of contingency plans to detect, control and eradicate such diseases. Diagnosis involves a ‘pipeline’ that normally starts with clinical suspicion, followed by collecting samples, transporting specimens to a centralised laboratory setting (e.g. national/international Reference Laboratories), analysing these samples using a range of diagnostic tests and reporting the results. However, the transport of specimens from the field to the laboratory can be a lengthy process that can delay critical decision-making and severely affect the quality of the samples. This important limitation of centralised diagnostic testing has motivated the development of tools for rapid, simple detection of livestock pathogens. Recent advances in the development of technologies for personalised human medicine have motivated the development of prototype diagnostic tests for a wide selection of diseases of livestock. However, many of these tests are not yet used routinely or are commercially available. This paper critically reviews the most promising examples of such assays, and highlights the challenges that remain to transition these tests from applied research and development into routine use.

Newman J, Asfor A S, Berryman S, Jackson T, Curry S, Tuthill T J (2017)

The cellular chaperone heat shock protein 90 is required for foot-and-mouth disease virus capsid precursor processing and assembly of capsid pentamers

Journal of Virology 92 (5), e01415-01417

Abstract

Productive picornavirus infection requires the hijack of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerisation of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and post-translational modification of the capsid precursor (P1-2A) by viral and cellular enzymes, and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation. We have developed a cell-free system to study FMDV pentamer assembly using recombinantly expressed FMDV capsid precursor and 3C protease. Using this assay, we have shown that two structurally different inhibitors of the cellular chaperone heat shock protein 90 (hsp90), impeded FMDV capsid precursor processing and subsequent pentamer formation. Treatment of FMDV permissive cells with the hsp90 inhibitor prior to infection reduced the endpoint titre by more than ten-fold while not affecting the activity of a sub-genomic replicon indicating that translation and replication of viral RNA were unaffected by the drug.IMPORTANCE Foot-and-mouth disease virus (FMDV), of the Picornaviridae family is a pathogen of huge economic importance to the livestock industry due to its effect on the restriction of livestock movement and necessary control measures required following an outbreak. The study of FMDV capsid assembly, and picornavirus capsid assembly more generally, has tended to be focused upon the formation of capsids from pentameric intermediates, or the immediate co-translational modification of the capsid precursor protein. Here we describe a system to analyse the early stages of FMDV pentameric capsid intermediate assembly and demonstrate a novel requirement for the cellular chaperone hsp90 in the formation of these pentameric intermediates. We show the added complexity involved for this process to occur which could be the bases for a novel antiviral control mechanism for FMDV.

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