Publications

Publications

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

There were a total of 2603 results for your search.

Abstract

The NKp46 receptor demonstrates a high degree of lineage specificity, being expressed almost exclusively in NK cells. Previous studies have demonstrated NKp46 expression by T cells, but NKp46+CD3+ cells are rare and almost universally associated with NKp46 acquisition by T cells following stimulation. In this study we demonstrate the existence of a population of NKp46+CD3+ cells resident in normal bovine PBMCs that includes cells of both the ?? TCR+ and ?? TCR+ lineages and is present at a frequency of 0.1–1.7%. NKp46+CD3+ cells express transcripts for a broad repertoire of both NKRs and TCRs and also the CD3?, DAP10, and Fc?R1? but not DAP12 adaptor proteins. In vitro functional analysis of NKp46+CD3+ cells confirm that NKp46, CD16, and CD3 signaling pathways are all functionally competent and capable of mediating/redirecting cytolysis. However, only CD3 cross-ligation elicits IFN-? release. NKp46+CD3+ cells exhibit cytotoxic activity against autologous Theileria parva–infected cells in vitro, and during in vivo challenge with this parasite an expansion of NKp46+CD3+ cells was observed in some animals, indicating the cells have the potential to act as an anti-pathogen effector population. The results in this study identify and describe a novel nonconventional NKp46+CD3+ T cell subset that is phenotypically and functionally distinct from conventional NK and T cells. The ability to exploit both NKRs and TCRs suggests these cells may fill a functional niche at the interface of innate and adaptive immune responses.
Crisci E, Fraile L, Valentino S, Martinez-Guino L, Bottazzi B, Mantovani A, Montoya M (2014)

Immune characterization of long pentraxin 3 in pigs infected with influenza virus

Veterinary Microbiology 168 (1), 185-192

Abstract

Long pentraxin 3 (PTX3) is a conserved pattern-recognition secreted protein and a hostdefence-related component of the humoral innate immune system. The aim of the present study was to characterize swine PTX3 (SwPTX3) protein expression in influenza virus infected pigs. First, we performed in silico studies to evaluate the cross-reactivity of PTX3 human antibodies against SwPTX3. Secondly, we used in vitro analysis to detect SwPTX3 presence in swine bone marrow dendritic cells (SwBMDC) upon stimulation with different agents by Western blot and immunofluorescence. Finally, the levels of SwPTX3 were assessed in experimental infection of pigs with different strains of influenza virus. This is a novel study where the expression of SwPTX3 was evaluated in the context of a pathogen infection. The initial characterization of SwPTX3 in influenza virus infected pigs contributes to understand the role of PTX proteins in the immune response.

Abstract

A complete phylogenetic analysis of all of the H9N2 hemagglutinin sequences that were collected between 1966 and 2012 was carried out in order to build a picture of the geographical and host specific evolution of the hemagglutinin protein. To improve the quality and applicability of the output data the sequences were divided into subsets based upon location and host species. The phylogenetic analysis of hemagglutinin reveals that the protein has distinct lineages between China and the Middle East, and that wild birds in both regions retain a distinct form of the H9 molecule, from the same lineage as the ancestral hemagglutinin. The results add further evidence to the hypothesis that the current predominant H9N2 hemagglutinin lineage might have originated in Southern China. The study also shows that there are sampling problems that affect the reliability of this and any similar analysis. This raises questions about the surveillance of H9N2 and the need for wider sampling of the virus in the environment. The results of this analysis are also consistent with a model where hemagglutinin has predominantly evolved by neutral drift punctuated by occasional selection events. These selective events have produced the current pattern of distinct lineages in the Middle East, Korea and China. This interpretation is in agreement with existing studies that have shown that there is widespread intra-country sequence evolution.
Dhanasekaran S, Biswas M, Vignesh A R, Ramya R, Raj G D, Tirumurugaan K G, Raja A, Kataria R S, Parida S, Subbiah E (2014)

Toll-Like receptor responses to peste des petits ruminants virus in goats and water buffalo

PLoS ONE 9 (11), e111609

Abstract

Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) ? in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFN? resulted in reduction of PPRV replication, confirming the role of IFN? in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFN? levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.

Abstract

Reconstructing the evolutionary history, demographic signal and dispersal processes from viral genome sequences contributes to our understanding of the epidemiological dynamics underlying epizootic events. In this study, a Bayesian phylogenetic framework was used to explore the phylodynamics and spatio-temporal dispersion of the O CATHAY topotype of foot-and-mouth disease virus (FMDV) that caused epidemics in the Philippines between 1994 and 2005. Sequences of the FMDV genome encoding the VP1 showed that the O CATHAY FMD epizootic in the Philippines resulted from a single introduction and was characterised by three main transmission hubs in Rizal, Bulacan and Manila Provinces. From a wider regional perspective, phylogenetic reconstruction of all available O CATHAY VP1 nucleotide sequences identified three distinct sub-lineages associated with country-based clusters originating in Hong Kong Special Administrative Region (SAR), the Philippines and Taiwan. The root of this phylogenetic tree was located in Hong Kong SAR, representing the most likely source for the introduction of this lineage into the Philippines and Taiwan. The reconstructed O CATHAY phylodynamics revealed three chronologically distinct evolutionary phases, culminating in a reduction in viral diversity over the final 10 years. The analysis suggests that viruses from the O CATHAY topotype have been continually maintained within swine industries close to Hong Kong SAR, following the extinction of virus lineages from the Philippines and the reduced number of FMD cases in Taiwan.

Abstract

The increasing global importance of Rift Valley fever (RVF) is clearly demonstrated by its geographical expansion. The presence of a wide range of host and vector species, and the epidemiological characteristics of RVF, have led to concerns that epidemics will continue to occur in previously unaffected regions of Africa. The proximity of the Sahrawi territories of Western Sahara to endemic countries, such as Mauritania, Senegal, and Mali with periodic isolation of virus and serological evidence of RVF, and the intensive livestock trade in the region results in a serious risk of RVF spread in the Sahrawi territories, and potentially from there to the Maghreb and beyond. A sero-epidemiological survey was conducted in the Saharawi territories between March and April 2008 to investigate the possible presence of the RVF virus (RVFV) and associated risk factors. A two-stage cluster sampling design was used, incorporating 23 sampling sites. A total of 982 serum samples was collected from 461 sheep, 463 goats and 58 camels. Eleven samples (0.97%) tested positive for IgG against the RVFV. There were clusters of high seroprevalence located mostly in the Tifariti (7.69%) and Mehaires (7.14%) regions, with the Tifariti event having been found in one single flock (4/26 positive animals). Goats and older animals were at a significantly increased risk being seropositive (p?=?0.007 and p?=?0.007, respectively). The results suggest potential RVF activity in the study area, where intense livestock movement and trade with neighbouring countries might be considered as a primary determinant in the spread of the disease. The importance of a continuous field investigation is reinforced, in light of the risk of RVF expansion to historically unaffected regions of Africa.

Abstract

A cohort based study has been undertaken to investigate the possible association of genetic polymorphisms in genes functionally related to follicular T helper (TfH) cells with non-responsiveness to hepatitis B virus (HBV) vaccination. A total of 24 single nucleotide polymorphisms (SNPs) in 6 TfH related genes(CXCR5, ICOS, CXCL13, IL-21, BCL6 and CD40L) were investigated in 20 non-responders and 45 responders to HBV vaccination. Genetic association analysis revealed that three SNPs (rs497916, rs3922, rs676925)in CXCR5 and one SNP (rs355687) in CXCL13 were associated with hepatitis B vaccine efficacy. In addition, significantly unbalanced distributions of two haplotypes, defined by three SNPs (rs497916, rs3922,rs676925) within CXCR5, were also seen between non-responders and responders. Furthermore, we demonstrated that the rs3922 “GG” genotype was associated with higher levels of CXCR5 than the “AG” and “AA” genotype in a group of healthy volunteers. A dual luciferase report assay was used to confirm that the “G” allele in rs3922 may lead to higher gene expression than the “A” allele, implicating that rs3922might be a functional SNP affecting CXCR5 expression. These results indicated that polymorphism asso-ciated changes in CXCR5 expression in TfH cells may be associated with non-responsiveness to hepatitis B vaccination.

Abstract

Current concerns about food security highlight the importance of maintaining productive and disease-resistant livestock populations. Major histocompatibility complex (MHC) class I genes have a central role in immunity. A high level of diversity in these genes allows populations to survive despite exposure to rapidly evolving pathogens. This review aims to describe the key features of MHC class I genetic diversity in cattle and to discuss their role in disease resistance. Discussion centers on data derived from the cattle genome sequence and studies addressing MHCclass I gene expression and function. The impact of intensive selection on MHC diversity is also considered.Ahigh level of complexity in MHC class I genes and functionally related gene families is revealed. This highlights the need for increased efforts to determine key genetic components that govern cattle immune responses to disease, which is increasingly important in the face of changing human and environmental demands.

Abstract

Newcastle disease (ND) is a highly contagious disease of many avian species and is particularly responsible for devastating disease outbreaks in commercial poultry flocks in Pakistan that incur huge economic losses to the national poultry industry annually. Despite implementation of an extensive vaccination program for poultry birds, the disease appears in an endemic form in commercial broiler and layer poultry farms. This study was conducted to identify the prevalent velogenic NDV strain responsible for disease outbreaks in commercial poultry farms in Punjab, Pakistan. The NDV strains isolated from pathological specimens through inoculation in embryonated chicken eggs were characterized biologically through the intracerebral pathogenicity index (ICPI), and genetically on the basis of the fusion (F) protein cleavage site. Among these, six NDV isolates showed an F protein cleavage site motif (112RRQKRF117) and an ICPI value ranging between 1.5 and 1.88, both are characteristics for velogenic strains of NDV. In addition, phylogenetic analysis based on a partial sequence of the F protein gene clustered these isolates within class II, genotype VII and specifically within genotype VII-e. This is the first report that demonstrated the presence of such NDV strains in commercial poultry farms in northern Punjab of Pakistan.

Abstract

Natural killer (NK) cells are important players in the innate immune response against influenza A virus and the activating receptor NKp46, which binds hemagglutinin on the surface of infected cells, has been assigned a role in this context. As pigs are natural hosts for influenza A viruses and pigs possess both NKp46 2 and NKp46(+) NK cells, they represent a good animal model for studying the role of the NKp46 receptor during influenza. We explored the role of NK cells in piglets experimentally infected with 2009 pandemic H1N1 influenza virus by flow cytometric analyses of cells isolated from blood and lung tissue and by immunostaining of lung tissue sections. The number of NKp46(+) NK cells was reduced while NKp46 2 NK cells remained unaltered in the blood 1-3 days after infection. In the lungs, the intensity of NKp46 expression on NK cells was increased during the first 3 days, and areas where influenza virus nucleoprotein was detected were associated with increased numbers of NKp46(+) NK cells when compared to uninfected areas. NKp46(+) NK cells in the lung were neither found to be infected with influenza virus nor to be undergoing apoptosis. The binding of porcine NKp46 to influenza virus infected cells was verified in an in vitro assay. These data support the involvement of porcine NKp46(+) NK cells in the local immune response against influenza virus.

Pages

Filter Publications

Trim content

® The Pirbright Institute 2024 | A company limited by guarantee, registered in England no. 559784. The Institute is also a registered charity.