Publications

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

There were a total of 2606 results for your search.
Brenner J, Oura C, Asis I, Maan S, Elad D, Maan N, Friedgut O, Nomikou K, Rotenberg D, Bumbarov V, Mertens P, Yadin H, Batten C (2010)

Multiple serotypes of bluetongue virus in sheep and cattle, Israel. (Letter)

Emerging Infectious Diseases 16 (12), 2003-2004
Buck A H, Perot J, Chisholm M A, Kumar D S, Tuddenham L, Cognat V, Marcinowski L, Dölken L, Pfeffer S (2010)

Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection

RNA 16 (2), 307-315

Abstract

In mammals, microRNAs (miRNAs) can play diverse roles in viral infection through their capacity to regulate both host and viral genes. Recent reports have demonstrated that specific miRNAs change in expression level upon infection and can impact viral production and infectivity. It is clear that miRNAs are an integral component of viral–host interactions, and it is likely that both host and virus contain mechanisms to regulate miRNA expression and/or activity. To date, little is known about the mechanisms by which miRNAs are regulated in viral infection. Here we report the rapid down-regulation of miR-27a in multiple mouse cell lines as well as primary macrophages upon infection with the murine cytomegalovirus. Down-regulation of miR-27a occurs independently from two other miRNAs, miR-23a and miR-24, located within the same genomic cluster, and analysis of pri-miRNA levels suggest that regulation occurs post-transcriptionally. miR-27b, a close homolog of miR-27a (20/21 nucleotide identity), also decreases upon infection, and we demonstrate that both miR-27a and miR-27b exert an antiviral function upon over-expression. Drug sensitivity experiments suggest that virus entry is not sufficient to induce the down-regulation of miR-27 and that the mechanism requires synthesis of RNA. Altogether, our findings indicate that miR-27a and miR-27b have antiviral activity against MCMV, and that either the virus or the host encodes molecule(s) for regulating miR-27 accumulation, most likely by inducing the rapid decay of the mature species.

Abstract

Campylobacter jejuni is a zoonotic bacterial pathogen of worldwide importance. It is estimated that 460,000 human infections occur in the United Kingdom per annum and these involve acute enteritis and may be complicated by severe systemic sequelae. Such infections are frequently associated with the consumption of contaminated poultry meat and strategies to control C. jejuni in poultry are expected to limit pathogen entry into the food chain and the incidence of human disease. Toward this aim, a total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium ?aroA vaccine expressing the C. jejuni amino acid binding protein CjaA as a plasmid-borne fusion to the C-terminus of fragment C of tetanus toxin. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4 log10 colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA. Protection was not observed using a vaccine strain containing the empty plasmid. Vaccination with recombinant CjaA subcutaneously at the same intervals significantly reduced the caecal load of C. jejuni at three and four weeks post-challenge. Taken together these data imply that responses directed against CjaA, rather than competitive or cross-protective effects mediated by the carrier, confer protection. The impact of varying parameters on the efficacy of the S. Typhimurium ?aroA vaccine expressing TetC-CjaA was also tested. Delaying the age at primary vaccination had little impact on protection or humoral responses to CjaA. The use of the parent strain as carrier or changing the attenuating mutation of the carrier to ?spaS or ?ssaU enhanced the protective effect, consistent with increased invasion and persistence of the vaccine strains relative to the ?aroA mutant. Expression in the ?aroA strain of a TetC fusion to Peb1A, but not TetC fusions to GlnH or ChuA, elicited protection against intestinal colonisation by C. jejuni that was comparable to that observed with the TetC-CjaA fusion. Our data are rendered highly relevant by use of the target host in large numbers and support the potential of CjaA- and Peb1A-based vaccines for control of C. jejuni in poultry.
Busquets N, Segales J, Cordoba L, Mussa T, Crisci E, Martin-Valls G E, Simon-Grife M, Perez-Simo M, Perez-Maillo M, Nunez J I, Abad F X, Fraile L, Pina S, Majo N, Bensaid A, Domingo M, Montoya M (2010)

Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus

Veterinary Research 41 (5), 74

Abstract

The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains.

Abstract

Salmonellosis is a frequent disease in poultry stocks, caused by several serotypes of the bacterial species Salmonella enterica and sometimes transmitted to humans through the consumption of contaminated meat or eggs. Symptom-free carriers of the bacteria contribute greatly to the propagation of the disease in poultry stocks. So far, several candidate genes and quantitative trait loci (QTL) for resistance to carrier state or to acute disease have been identified using artificial infection of S. enterica serovar Enteritidis or S. enterica serovar Typhimurium strains in diverse genetic backgrounds, with several different infection procedures and phenotypic assessment protocols. This diversity in experimental conditions has led to a complex sum of results, but allows a more complete description of the disease. Comparisons among studies show that genes controlling resistance to Salmonella differ according to the chicken line studied, the trait assessed and the chicken's age. The loci identified are located on 25 of the 38 chicken autosomal chromosomes. Some of these loci are clustered in several genomic regions, indicating the possibility of a common genetic control for different models. In particular, the genomic regions carrying the candidate genes TLR4 and SLC11A1, the Major Histocompatibility Complex (MHC) and the QTL SAL1 are interesting for more in-depth studies. This article reviews the main Salmonella infection models and chicken lines studied under a historical perspective and then the candidate genes and QTL identified so far.

Cantaloube J F, Gallian P, Bokilo A, Jordier F, Biagini P, Attoui H, Chiaroni J, de M P (2010)

Analysis of hepatitis C virus strains circulating in Republic of the Congo

Journal of Medical Virology 82 (4), 562-567

Abstract

The aim of this study was to assess the seroprevalence, viremia, genotype distribution, and demographic history of hepatitis C virus (HCV) in the Republic of the Congo. Testing was carried out on sera samples collected in 2005 from 807 Bantus belonging to the Kongo, Teke, and Ngala subgroups and 80 Pygmies. Positive HCV serology was found in 50 (5.6%) individuals including 31 (60%) who were viremic. Seroprevalence increased with age with a cutoff at 50 years: 2.8% 50. Twenty-one strains belonged to four described subtypes, that is, 4c in eight cases, 4h in two, 4k in three, and 4r in eight. Ten strains could not be assigned to any known subtype and may represent six new variants, that is, subtype 4 in five cases and subtype 2 in one. Evolutionary analysis of subtype 4c and 4r sequences indicated a period of enhanced transmission in the mid-twentieth century probably due to iatrogenic causes. This study underlines the high genetic diversity of strains in the Republic of the Congo with nine subtypes 4 and one subtype 2.

Abstract

VP2 is the outermost Bluetongue virus (BTV) antigenic protein, forming triskelion motifs on the virion surface. Although VP2 has been expressed successfully through many systems, its paracrine expression as a soluble form by mammalian cells represents a difficult task In the present paper two fragments of VP2 have been expressed successfully into the medium of transiently transfected mammalian cells through a fusion peptides strategy. The crude conditioned medium containing the secreted peptide could be employed for immunodiagnostic assay development or vaccine purposes.
Chaignat V, Schwermer H, Casati S, Planzer J, Worwa G, Vanzetti T, Batten C, Hofmann M, Thur B (2010)

Occurrence and spatial distribution of Toggenburg Orbivirus in Switzerland

Small Ruminant Research 93 (2-3), 157-164

Abstract

Recently, a new member of the Bluetongue virus (BTV) serogroup named Toggenburg Orbivirus (TOV) in goats from Switzerland has been described. The epidemiology and host range of TOV are currently unknown. Since TOV causes cross-reactions in laboratory tests used for BTV diagnosis, this study was carried out in order to determine the spatial and temporal spread of TOV. Therefore, serum samples from a national survey in goats, collected during winter and spring 2008 in Switzerland, were serologically examined. Additionally, cattle and sheep from holdings with seropositive goats were tested for the presence of viral RNA and antibodies against BTV and TOV. All goat samples analysed within routine diagnostics at the Institute of Virology and Immunoprophylaxis from 2008 to 2009 were also tested for the presence of TOV. Finally, goat sera collected 1998 in the Canton of Ticino (TI) were analysed. Although the TOV index cases had been identified in flocks north of the Alps, no additional TOV-positive herds were found by serological testing in this region. In contrast, south of the Alps, i.e. in the Canton of Ticino (TI), an apparent seroprevalence of 49% in goats was found at animal and 60% at herd level. In the eastern and western part of the Swiss Alps 15.2% and 10% of tested goats were serologically positive, respectively. A within-herd prevalence of up to 100% was found in some of the positive flocks. The positive flocks in TI were mainly found in three of the five districts, but seropositive animals were identified in each district. Certain selected seropositive flocks were investigated virologically. By RT-qPCR and genome sequencing, the presence of TOV could be confirmed in all investigated seropositive flocks. By testing the goats within routine diagnostics. TOV genome was detected in one goat showing BT-like clinical symptoms from the central Alps and in three healthy animals imported from Germany. Although 3.8% of the sheep from flocks with TOV-positive goats or in contact with these animals showed a positive antibody reaction, TOV-specific RNA was not found in any of the tested sheep and also not in cattle from flocks with TOV-positive goats.

Abstract

To determine the longevity of protective immunity following a single administration of emergency vaccine, and establish whether the immune response could be enhanced by increasing the antigen payload even further, cattle were vaccinated with an A22 Iraq vaccine containing either 1 x antigen payload (field dose) or 5x antigen payload. Six months post-immunisation all cattle received a homologous virus challenge. The magnitude of the virus neutralising antibody response elicited was consistent with the response to similarly formulated A serotype vaccines with a PD(50) greater than 32. All the vaccinated cattle, regardless of antigen payload, were protected from clinical disease following challenge although some cattle in both groups became sub-clinically infected. We conclude that immunisation with a single inoculation of vaccine from the UK emergency reserve can protect cattle from clinical disease for at least 6 months post-vaccination and that a boost may be unnecessary in an outbreak situation. Some animals may become sub-clinically infected but this is likely to be dependent on the severity of challenge. The study confirmed that a booster at 21 days post-vaccination was not necessary to maintain a cell-mediated response in cattle for 6 months. No increased benefits were recognised by increasing the antigen payload of this vaccine 5x.

Abstract

Porcine circovirus type 2 (PCV2) is the essential etiological agent of postweaning multisystemic wasting syndrome (PMWS), a worldwide distributed pig disease. The involvement of the immune system in the pathogenesis of PMWS is considered crucial. Previous studies have shown a cytokine profile suggesting T immunosuppression and indicating that interleukin 10 (IL-10) may play an important role during PCV2 infection. Nine 11- to 12-week-old conventional pigs were obtained from commercial farms located in North-Eastern Spain with historical records of PMWS. Spleen from four healthy and five PMWS-affected animals were collected at the necropsy. Viral load was determined in serum by means of standard PCR and real-time quantitative PCR. Phenotype and distribution of different immune cells involved in IL-10 secretion in the spleen of studied pigs were analysed using immunofluorescent assays. The CD163(+), CD4(+), and CD8(+) cell subpopulations produced IL-10 in the spleen and IL-10(+) cell numbers were higher in PMWS animals compared with their healthy counterparts. Furthermore. IL-10 producing cells were not infected by PCV2 and were mainly localized in the periarteriolar lymphoid sheaths. This is the first immunophenotyping study on IL-10 producing cells in cases of PMWS, further extending the studies on the role of IL-10 in disease pathogenesis.

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