Publications

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

There were a total of 2599 results for your search.
Howey R, Bankowski B, Juleff N, Savill N J, Gibson D, Fazakerley J, Charleston B, Woolhouse M E J (2012)

Modelling the within-host dynamics of the foot-and-mouth disease virus in cattle

Epidemics 4 (2), 93-103

Abstract

In this paper we investigate the within-host dynamics of the foot-and-mouth disease virus (FMDV) in cattle using previously published data for 8 experimentally infected cows. An 8-compartment, 14-parameter differential equation model was fitted to data collected from each cow every 24 h over the course of an infection on: (i) the concentration of FMDV genomes in the blood, (ii) the concentration of infectious virus in the blood, (iii) antibody levels, and (iv) interferon levels. Model parameters were estimated using maximum-likelihood methods. The likelihood surface was sampled using Markov chain Monte Carlo methods giving credible intervals for each of the model parameters. The model was able to capture the within-host dynamics well for 6 of the infections, with both the innate (type 1 interferon) and antibody responses playing key roles in determining the height and duration of peak levels of virus. There was considerable variation between virus dynamics in individual cattle which was only partly accounted for by inferred differences in the dose of virus received. A better understanding of the within-host dynamics also provides insights into the dynamics of infectiousness and the transmission of virus to new hosts.

Abstract

Peste des petits ruminants virus (PPRV) causes high mortality in goats and sheep and the disease has shown a greatly increased geographic distribution over the last 15 years. It is responsible for serious socioeconomic problems in some of the poorest developing countries. The ability to create recombinant PPRV would provide a useful tool for investigating the biology of the virus and the pathology of disease, as well as for developing new vaccines and diagnostic methods. Here we report the first successful rescue of recombinant PPRV from a full-length cDNA clone of the virus genome. Successful recovery of PPRV was achieved by using a RNA polymerase II promoter to drive transcription of the full-length virus antigenome. We have used this technique to construct a virus expressing a tracer protein (green fluorescent protein, GFP). The recombinant virus replicated as well as the parental virus and could stably express GFP during at least 10 passages. The newly established reverse genetics system for PPRV provides a novel method for constructing a vaccine using PPRV as a vector, and will also prove valuable for fundamental research on the biology of the virus. We found that our recombinant virus allowed more rapid and higher throughput assessment of PPRV neutralization antibody titer via the virus neutralization test (VNT) compared with the traditional method.

Abstract

Interactions between the early-life colonising intestinal microbiota and the developing immune system are critical in determining the nature of immune responses in later life. Studies in neonatal animals in which this interaction can be examined are central to understanding the mechanisms by which the microbiota impacts on immune development and to developing therapies based on manipulation of the microbiome. The inbred piglet model represents a system that is comparable to human neonates and allows for control of the impact of maternal factors. Here we show that colonisation with a defined microbiota produces expansion of mucosal plasma cells and of T-lymphocytes without altering the repertoire of alpha beta T-cells in the intestine. Importantly, this is preceded by microbially-induced expansion of a signal regulatory protein ?-positive (SIRP?+) antigen-presenting cell subset, whilst SIRP??CD11R1+ antigen-presenting cells (APCs) are unaffected by colonisation. The central role of intestinal APCs in the induction and maintenance of mucosal immunity implicates SIRP?+ antigen-presenting cells as orchestrators of early-life mucosal immune development.

Abstract

Vaccination is the most cost effective strategy for the control and prevention of the plethora of viral diseases affecting poultry production. The major challenge for poultry vaccination is the design of vaccines that will protect against multiple pathogens via a single protective dose, delivered by mass vaccination. The Marek disease virus and the highly pathogenic avian influenza virus cause severe disease outbreaks in chickens. Vaccination with live herpesvirus of turkeys protects chickens from Marek disease and inactivated influenza viruses are used as antigens to protect chickens against influenza virus infections. We developed herpesvirus of turkeys (HVT) as a vaccine vector that can act as a dual vaccine against avian influenza and Marek disease. The HVT vector was developed using reverse genetics based on an infectious bacterial artificial chromosome (BAC) clone of HVT. The BAC carrying the HVT genome was genetically modified to express the haemagglutinin (HA) gene of a highly pathogenic H7N1 virus. The resultant recombinant BAC construct containing the modified HVT sequence was transfected into chicken embryo fibroblast (CEF) cells and HVT recombinants (rHVT-H7HA) harbouring the H7N1 HA were recovered. Analysis of cultured CEF cells infected with the rHVT-H7HA showed that HA was expressed and that the rescued rHVT-H7HA stocks were stable during several in vitro passages with no difference in growth kinetics compared with the parent HVT. Immunization of one-day-old chicks with rHVT-H7HA induced H7-specific antibodies and protected chickens challenged with homologous H7N1 virus against virus shedding, clinical disease and death. The rHVT-H7HA vaccine also induced strong and long-lasting antibody titers against H7HA in chickens that were vaccinated in ovo 3 d before hatching. This vaccine supports differentiation between infected and vaccinated animals (DIVA), because no influenza virus nucleoprotein-specific antibodies were detected in the rHVT-H7HA vaccinated birds. The rHVT-H7HA not only provided protection against a lethal challenge with highly pathogenic H7N1 virus but also against highly virulent Marek disease virus and can be used as a DIVA vaccine.

Abstract

The influence of different glycosylation patterns of the haemagglutinin glycoprotein of H7N1 avian influenza viruses on virus replication in vivo was examined. Experimental infection of chickens and turkeys was carried out with H7N1 avian influenza viruses with alternative sites of glycosylation in the haemagglutinin and infected birds were sampled daily by swabbing the buccal and cloacal cavities. cDNAs of the HA1 coding region of the HA gene were prepared from the swabs and cloned into plasmids. Sequencing multiple plasmids made from individual swabs taken over the period of virus shedding showed that viruses with specific patterns of glycosylation near the receptor binding site were stable when birds were infected with a single variant, but when presented with a mixed population of viruses encoding differing patterns of glycosylation a specific variant was rapidly selected in the infected host.
Jack C, Anstaett O, Adams J, Noad R, Brownlie J, Mertens P (2012)

Evidence of seroconversion to SBV in camelids (Letter)

Veterinary Record 170 (23), 603
Publisher’s version: http://dx.doi.org/10.1136/vr.e3939

Abstract

At the Royal Veterinary College (RVC), we are conducting a longitudinal serosurveillance of the livestock (about 150 cattle, 1250 sheep and 10 alpacas) on our farm for evidence of Schmallenberg virus (SBV) infection. There have already been three proven cases of SBV in our newborn lambs (born on February 1 and 7 and March 30). We have taken blood samples from all animals during spring 2012 to examine the extent of infection and it is our intention to re-sample them during June to provide data for any further and more recent transmission during the new Culicoides species midge season. Our alpacas were bled in March 2012. SBV serology was assessed by the ID Screen Schmallenberg Virus Indirect ELISA (ID.vet). The outcome of this survey will be published later. The purpose of this letter is to record that two of 10 alpacas have SBV antibodies (a higher percentage than we have recorded to date in our sheep and cattle) and to highlight this finding to practitioners who might have alpacas in their care. No associated clinical problems have been recorded in these alpacas. We are unaware of any other publication of SBV infection in camelids.
Juleff N D, Maree F F, Waters R, Bengis R G, Charleston B (2012)

The importance of FMDV localisation in lymphoid tissue

Veterinary Immunology and Immunopathology 148 (1-2), 145-148

Abstract

Foot-and-mouth disease virus, a highly contagious pathogen that can cause lameness, low weight and decreased milk production, is a scourge of agricultural livestock around the world. Although the acute phase of infection is rarely fatal, infection may persist in animals that have apparently recovered, creating a viral reservoir that some fear could contribute to the spread of disease. We have used an array of molecular techniques to search for traces of virus in tissues from the mouths and throats of infected cattle. In a carefully controlled study, we have found evidence of intact, non-replicating virus particles trapped by follicular dendritic cells within the germinal centres of lymph nodes. Strikingly, virus was present for up to 38 days post infection, even though it was undetectable in surrounding tissues. The retention of intact virus within germinal centres is likely to have a role in stimulating the long lasting immune response that is characteristic of viral infections. Our data suggests that this capture may also be responsible for preserving intact viruses capable of infecting susceptible cells as they come into contact with germinal centres. African buffalo (Syncerus caffer) are typically infected with all three South African Territories types of FMDV by 2 years of age and these viruses can be transmitted to farmed livestock. Buffalo harbour persistent virus in greater amounts and for longer periods than cattle and thus provided us with further opportunities to define the sites of viral localisation.
Kasanga C J, Sallu R, Kivaria F, Mkama M, Masambu J, Yongolo M, Das S, Mpelumbe-Ngeleja C, Wambura P N, King D P, Rweyemamu M M (2012)

Foot-and-mouth disease virus serotypes detected in Tanzania from 2003 to 2010: conjectured status and future prospects

Onderstepoort Journal of Veterinary Research 79 (2), e462

Abstract

This study was conducted to investigate the presence of foot-and-mouth disease virus (FMDV) in different geographic locations of Tanzania. Epithelial tissues and fluids (n = 364) were collected from cattle exhibiting oral and foot vesicular lesions suggestive of FMD and submitted for routine FMD diagnosis. The analysis of these samples collected during the period of 2002 and 2010 was performed by serotype-specific antigen capture ELISA to determine the presence of FMDV. The results of this study indicated that 167 out of 364 (46.1%) of the samples contained FMDV antigen. Of the 167 positive samples, 37 (28.4%) were type O, 7 (4.1%) type A, 45 (21.9%) SAT 1 and 79 (45.6%) SAT 2. Two FMDV serotypes (O and SAT 2) were widely distributed throughout Tanzania whilst SAT 1 and A types were only found in the Eastern zone. Our findings suggest that serotypes A, O, SAT 1 and SAT 2 prevail in Tanzania and are associated with the recent FMD outbreaks. The lack of comprehensive animal movement records and inconsistent vaccination programmes make it difficult to determine the exact source of FMD outbreaks or to trace the transmission of the disease over time. Therefore, further collection and analysis of samples from domestic and wild animals are being undertaken to investigate the genetic and antigenic characteristics of the circulating strains, so that a rational method to control FMD in Tanzania and the neighbouring countries can be recommended.
King D P, Madi M, Mioulet V, Wadsworth J, Wright C F, Valdazo-Gonzalez B, Ferris N P, Knowles N J, Hammond J (2012)

New technologies to diagnose and monitor infectious diseases of livestock: Challenges for sub-Saharan Africa

Onderstepoort Journal of Veterinary Research. 79 (2), e456

Abstract

Using foot-and-mouth disease (FMD) as an example, this review describes new tools that can be used to detect and characterise livestock diseases. In recent years, molecular tests that can detect and characterise pathogens in a diverse range of sample types have revolutionised laboratory diagnostics. In addition to use in centralised laboratories, there are opportunities to locate diagnostic technologies close to the animals with suspected clinical signs. Work in this area has developed simple-to-use lateral-flow devices for the detection of FMD virus (FMDV), as well as new hardware platforms to allow molecular testing to be deployed into the field for use by non-specialists. Once FMDV has been detected, nucleotide sequencing is used to compare field strains with reference viruses. Transboundary movements of FMDV are routinely monitored using VP1 sequence data, while higher resolution transmission trees (at the farm-to-farm level) can be reconstructed using full-genome sequencing approaches. New technologies such as next-generation sequencing technologies are now being applied to dissect the viral sequence populations that exist within single samples. The driving force for the use of these technologies has largely been influenced by the priorities of developed countries with FMD-free (without vaccination) status. However, it is important to recognise that these approaches also show considerable promise for use in countries where FMD is endemic, although further modifications (such as sample archiving and strain and serotype characterisation) may be required to tailor these tests for use in these regions. Access to these new diagnostic and sequencing technologies in sub-Saharan Africa have the potential to provide novel insights into FMD epidemiology and will impact upon improved strategies for disease control. Effective control of infectious diseases is reliant upon accurate diagnosis of clinical cases using laboratory tests, together with an understanding of factors that impact upon the epidemiology of the infectious agent. A wide range of new diagnostic tools and nucleotide sequencing methods are used by international reference laboratories to detect and characterise the agents causing outbreaks of infectious diseases. In the past, high costs (initial capital expenses, as well as day-to-day maintenance and running costs) and complexity of the protocols used to perform some of these tests have limited the use of these methods in smaller laboratories. However, simpler and more cost-effective formats are now being developed that offer the prospect that these technologies will be even more widely deployed into laboratories particularly those in developing regions of the world such as sub-Saharan Africa.
Knowles N J, He J J, Shang Y J, Wadsworth J, Valdazo-Gonzalez B, Onosato H, Fukai K, Morioka K, Yoshida K, Cho I S, Kim S M, Park J H, Lee K N, Luk G, Borisov V, Scherbakov A, Timina A, Bold D, Nguyen T, Paton D J, Hammond J M, Liu X T, King D P (2012)

Southeast Asian foot-and-mouth disease viruses in Eastern Asia

Emerging Infectious Diseases 18 (3), 499-501

Abstract

Foot-and-mouth disease (FMD) outbreaks recently affected 2 countries (Japan and South Korea) in eastern Asia that were free of FMD without vaccination. Analysis of viral protein 1 nucleotide sequences indicated that FMD serotype A and 0 viruses that caused these outbreaks originated in mainland Southeast Asia to which these viruses are endemic.

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