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.

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine worldwide. Since its first emergence in 1987 the PARS virus (PRRSV) has become particularly divergent with highly pathogenic strains appearing in both Europe and Asia. However, the underlying mechanisms of PRRSV pathogenesis are still unclear. This study sets out to determine the differences in pathogenesis between subtype 1 and 3 strains of European PRRSV (PRRSV-I), and compare the immune responses mounted against these strains. Piglets were infected with 3 strains of PRRSV-I: Lelystad virus, 215-06 a British field strain and SU1-bel from Belarus. Post-mortem examinations were performed at 3 and 7 days post-infection (dpi), and half of the remaining animals in each group were inoculated with an Aujeszky's disease (ADV) vaccine to investigate possible immune suppression resulting from PRRSV infection. The subtype 3 SU1-bel strain displayed greater clinical signs and lung gross pathology scores compared with the subtype 1 strains. This difference did not appear to be caused by higher virus replication, as viraemia and viral load in broncho-alveolar lavage fluid (BALF) were lower in the SU1 -bel group. Infection with SU1 -bel induced an enhanced adaptive immune response with greater interferon (IFN)-gamma responses and an earlier PRRSV-specific antibody response. Infection with PRRSV did not affect the response to vaccination against ADV. Our results indicate that the increased clinical and pathological effect of the SU1 -bel strain is more likely to be caused by an enhanced inflammatory immune response rather than higher levels of virus replication.
Mulabbi E N, Ayebazibwe C, Majalija S, Batten C A, Oura C A L (2013)

Circulation of bluetongue virus in goats in the Karamoja region of Uganda

Journal of the South African Veterinary Association 84 (1), E1-E3

Abstract

The presence of bluetongue virus (BTV) in indigenous goats from the Karamoja region of northern Uganda was investigated. A total of 300 goats were sampled (serum and whole blood) from five districts within the Karamoja region. The samples were analysed for the presence of bluetongue (BT) antibodies using a commercial Enzyme-linked immunosorbent assay (ELISA) and for the presence of BTV viral RNA by real-time Reverse transcription polymerase chain reaction (RT-PCR), because BTV is an RNA virus. Of the 300 goats tested, 269 (90%) were positive for BTV antibodies, indicating high levels of BTV circulation within the region. Out of the 150 whole blood samples tested for the presence of the virus by real-time RT-PCR, 84 (56%) were positive for BTV RNA. This study, which is the first of its kind in Uganda, showed a high seroprevalence of BT antibodies and active circulation of BTV in a high proportion of goats in the Karamoja region.
Mullarkey C E, Boyd A, van Laarhoven A, Lefevre E A, Carr B V, Baratelli M, Molesti E, Temperton N J, Butter C, Charleston B, Lambe T, Gilbert S C (2013)

Improved adjuvanting of seasonal influenza vaccines: Preclinical studies of MVA-NP+M1 coadministration with inactivated influenza vaccine

European Journal of Immunology 43 (7), 1940-1952

Abstract

Licensed seasonal influenza vaccines induce antibody (Ab) responses against influenza hemagglutinin (HA) that are limited in their ability to protect against different strains of influenza. Cytotoxic T lymphocytes recognizing the conserved internal nucleoprotein (NP) and matrix protein (M1) are capable of mediating a cross-subtype immune response against influenza. Modified vaccinia Ankara (MVA) virus encoding NP and M1 (MVA-NP+M1) is designed to boost preexisting T-cell responses in adults in order to elicit a cross-protective immune response. We examined the coadministration of HA protein formulations and candidate MVA-NP+M1 influenza vaccines in murine, avian, and swine models. Ab responses postimmunization were measured by ELISA and pseudotype neutralization assays. Here, we demonstrate that MVA-NP+M1 can act as an adjuvant enhancing Ab responses to HA while simultaneously inducing potent T-cell responses to conserved internal Ags. We show that this regimen leads to the induction of cytophilic Ab isotypes that are capable of inhibiting hemagglutination and in the context of H5 exhibit cross-clade neutralization. The simultaneous induction of T cells and Ab responses has the potential to improve seasonal vaccine performance and could be employed in pandemic situations.

Abstract

Due to a significant decrease in the cost of DNA sequencing, the number of sequences submitted to the public databases has dramatically increased in recent years. Efficient analysis of these data sets may lead to a significant understanding of the nature of pathogens such as bacteria, viruses, parasites, etc. However, this has raised questions about the efficacy of currently available algorithms for the study of pathogen evolution and construction of phylogenetic trees. While the advanced algorithms and corresponding programs are being developed, it is crucial to optimize the available ones in order to cope with the current need. The protocol presented in this study is optimized using a number of strategies currently being proposed for handling large-scale DNA sequence data sets, and offers a highly efficacious and accurate method for computing phylogenetic trees with limited computer resources. The protocol may take up to 36 h for construction and annotation of a final tree of about 20,000 sequences.

Abstract

The purpose of this book is to provide a timely and comprehensive review on all the mononegaviruses of veterinary importance. The book is divided into two sections. Section I deals with 13 mononegaviruses (Bornaviruses, Avian Paramyxoviruses serotypes 1 to 10, Hendra and Nipah viruses, Canine distemper virus, Peste des petits ruminants virus, Rinderpest virus, Bovine parainfluenza virus, Swine parainfluenza virus, Porcine rubulavirus (PoRV -LPMV), Bovine respiratory syncytial virus, Avian metapneumoviruses, Bovine ephemeral fever virus and Rabies virus) of livestock, horses, dogs and cats; whereas Section II comprises of 9 other mononegaviruses (Ebolavirus, Marburgvirus, Phocine distemper virus, Morbilliviruses, Sendai virus, pneumonia virus, Infectious hematopoietic necrosis virus, Viral haemorrhagic septicaemia virus and Snakehead rhabdovirus) of rodents, primates, fish and sea mammals. A full chapter is dedicated to each virus which provides up-to-date literature on historical distribution, genome structure, viral proteins, reverse genetics, immunity, viral pathogenesis, clinical and molecular diagnosis and future challenges. Every chapter is written by renowned scientists who have made seminal contributions in their respective mononegavirus fields of expertise. Each chapter is attempted to make as stand-alone document, making it a valuable reference source for virologists, field veterinarians, infection and molecular biologists, immunologists, scientists in related fields and veterinary school libraries.

Abstract

Various pattern recognition receptors (PRRs) have been implicated in the detection of viral RNA and subsequent interferon (IFN) gene expression, including the double-stranded RNA-dependent proteinkinase R (PKR). Now, a novel role of PKR has been unveiled, as it was shown that, upon the infection with certain viruses, PKR is crucial for the integrity of newly synthesized IFN mRNA, thereby generating an optimal host antiviral immune response. There is a need of future studies to investigate additional roles of PKR in innate immunity and the molecular understanding of this novel function of PKR.

Abstract

Several outbreaks of avian influenza (AI) caused by H9N2 subtype, have been reported in the poultry industry during 1990 around the globe. Currently, H9N2 are endemic in the large area of Middle and Far East, including Pakistan. Since H9N2 AI viruses are sporadically reported from humans, extensive incidence of H9N2 in poultry imposes a great risk for human health. In this context, continuous monitoring of the poultry and determining the genetic nature of these viruses are fundamental to predict any future threat. Thus gene sequences of one isolate of H9N2, isolated from commercial poultry flocks, were analyzed. The results of this investigation, based on hemagglutinin (HA), neuraminidase (NA) and non-structural genes, showed that Pakistani H9N2 isolates are closely related to each other and to other H9N2 isolates from the Middle East. However, several unusual substitutions with unknown functional consequences were observed in HA and NA proteins and thus warrant further investigations for their possible role in viral biology. In conclusion, these findings provide information regarding the genetic nature of H9N2 avian influenza viruses in Pakistani poultry and necessitate the sequencing of more H9N2 viruses from both naturally infected and vaccinated flocks.
Munir M, Zohari S, Berg M (2013)

Molecular Biology and Pathogenesis of Peste des Petits Ruminants Virus. (book)

, 151

Abstract

Peste de Petits Ruminants (PPR) is a highly contagious viral disease of domestic and wild small ruminants that can significantly affect economies. The authors are experts in the field and provide an up-to-date and comprehensive review covering all aspects of the disease. The book is divided into seven chapters highlighting genome organization, virus replication and the determinants of virulence, pathophysiology and clinical disease, immunology and immunopathogenesis, epidemiology, diagnostic assays and vaccines, and the challenges concerning global eradication. It is an invaluable reference work, presenting the latest information for virologists, microbiologists, immunologists, veterinarians, and scientists working in PPR research.

Abstract

Apart from natural reassortment, co-circulation of different avian influenza virus strains in poultry populations can lead to generation of novel variants and reassortant viruses. In this report, we studied the genetics and functions of a reassorted non-structural gene (NS) of H9N2 influenza virus collected from back yard poultry (BYP) flock. Phylogenetic reconstruction based on hemagglutinin and neuraminidase genes indicates that an isolate from BYP belongs to H9N2. However, the NS gene-segment of this isolate cluster into genotype Z, clade 2.2 of the highly pathogenic H5N1. The NS gene plays essential roles in the host-adaptation, cell-tropism, and virulence of influenza viruses. However, such interpretations have not been investigated in naturally recombinant H9N2 viruses. Therefore, we compared the NS1 protein of H9N2 (H9N2/NS1) and highly pathogenic H5N1 (H5N1/NS1) in parallel for their abilities to regulate different signaling pathways, and investigated the molecular mechanisms of IFN-beta production in human, avian, and mink lung cells. We found that H9N2/NS1 and H5N1/NS1 are comparably similar in inhibiting TNF-alpha induced nuclear factor kappaB and double stranded RNA induced activator protein 1 and interferon regulatory factor 3 transcription factors. Thus, the production of IFN-beta was inhibited equally by both NS1s as demonstrated by IFN stimulatory response element and IFN-beta promoter activation. Moreover, both NS1s predominantly localized in the nucleus when transfected to human A549 cells. This study therefore suggests the possible increased virulence of natural reassortant viruses for their efficient invasion of host immune responses, and proposes that these should not be overlooked for their epizootic and zoonotic potential.

Abstract

Here, we announce the first complete genome sequence of a field isolate of a peste des petits ruminants virus (PPRV) from northern Africa. This isolate is derived from an Alpine goat that suffered from severe clinical disease during the 2008 outbreak in Morocco. The full genome sequence of this isolate clusters phylogenetically with the lineage IV isolates of PPRV, sharing high levels of sequence identity with other lineage IV isolates.

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