Publications

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

There were a total of 2609 results for your search.

Abstract

Background: Bluetongue (BT) is a viral disease of ruminants transmitted by Culicoides biting midges and has the ability to spread rapidly over large distances. In the summer of 2006, BTV serotype 8 (BTV-8) emerged for the first time in northern Europe, resulting in over 2000 infected farms by the end of the year. The virus subsequently overwintered and has since spread across much of Europe, causing tens of thousands of livestock deaths. In August 2007, BTV-8 reached Great Britain (GB), threatening the large and valuable livestock industry. A voluntary vaccination scheme was launched in GB in May 2008 and, in contrast with elsewhere in Europe, there were no reported cases in GB during 2008. Methodology/Principal Findings: Here, we use carefully parameterised mathematical models to investigate the spread of BTV in GB and its control by vaccination. In the absence of vaccination, the model predicted severe outbreaks of BTV, particularly for warmer temperatures. Vaccination was predicted to reduce the severity of epidemics, with the greatest reduction achieved for high levels (95%) of vaccine uptake. However, even at this level of uptake the model predicted some spread of BTV. The sensitivity of the predictions to vaccination parameters (time to full protection in cattle, vaccine efficacy), the shape of the transmission kernel and temperature dependence in the transmission of BTV between farms was assessed. Conclusions/Significance: A combination of lower temperatures and high levels of vaccine uptake (>80%) in the previously-affected areas are likely to be the major contributing factors in the control achieved in England in 2008. However, low levels of vaccination against BTV-8 or the introduction of other serotypes could result in further, potentially severe outbreaks in future

Abstract

The complete nucleotide sequence of Great Island virus (GIV) genome was determined, along with genome segments (Seg) 1, 2 and 6 of Kemerovo (KEMV), Lipovnik (LIPV) and Tribec (TRBV) viruses All four viruses, together with Broadhaven virus, are currently classified within the species Great Island virus and have been isolated from ticks, birds or humans Sequence comparisons showed that Seg-4 of GIV encoded the outer-capsid protein responsible for cell attachment, although it was approximately half the length of its counterpart in the Culicoides or mosquito-transmitted orbiviruses A second overlapping ORF (in the +2 reading frame) was identified in Seg-9 of GIV, encoding a putative dsRNA-binding protein Phylogenetic analyses of the RNA-dependent RNA polymerase (Pal) and 12 protein amino acid sequences indicated that the tick-borne orbiviruses represent an ancestral group from which the mosquito-borne orbiviruses have evolved This mirrors the evolutionary relationships between the arthropod vectors of these viruses, supporting a co-speciation hypothesis for these arboviruses and their arthropod-vectors Phylogenetic analyses of the 12 proteins of KEMV, LIPV, TRBV and GIV (showing 82% amino acid identity) correlated with the early classification of Great Island viruses as two distinct serocomplexes (Great Island and Kemerovo serocomplexes) Amino acid identity levels in the VP1(Pol) and T2 proteins between the two serocomplexes were 73 and 82%, respectively, whilst those between previously characterized Orbivirus species are 53-73% and 26-83%, respectively These data suggest that despite limited genome segment reassortment between these two groups, their current classification within the same Orbivirus species could be re-evaluated
Botner A, Pena A E, Mannelli A, Wieland B, Potzsch C, Patta C, Albina E, Boinas F, Koenen F, Sharp J M, Dixon L, Salman M, Sanchex V, Blome S, Guberti V, Dhollander S, Georgiev M, Tarres J, Goumperis T (2010)

Scientific opinion on African swine fever

EFSA Journal 8 (3), 1556 [149 pp.]

Abstract

The risk that African Swine Fever virus (ASFV) remains endemic in the Trans Caucasian Countries (TCC) and the Russian Federation (RF) is moderate, while the risk of its spread in these regions is high. The resulting risk of introduction from these regions into the EU is moderate most likely through food waste. The risk of ASFV remaining endemic in wild boar and the consequent introduction into the EU was considered low in the TCC and moderate in the RF, mainly due to the higher population density in the RF and the connected wild boar populations to the EU from the RF. Within the EU, mainly domestic pigs in the free range (FR) and the limited biosecurity sector (LB) are likely to be exposed to ASFV via swill feeding, with low risk. Once infected, the risk of spread from the LB and FR sectors prior detection is high, mainly due to movement of pigs, people and vehicles and moderate from the High Biosecurity (HB) sector. The risk of endemicity in domestic pigs is considered negligible in HB and low in LB since the implementation of control measures are effective. The risk of endemicity in the FR sector is moderate due to wild boar contact, non-compliance with animal movement ban and difficult access to all individual pigs. The risk of ASFV becoming endemic in the wild boar population in the EU is moderate, in particular in areas with connected wild boar populations. Because of their long life, ticks of the O. erraticus complex can be important in maintaining local foci of ASFV, where pigs are kept under traditional systems. Ticks do not, play an active role in the geographical spread of the virus. Wild boar have never been found infested because they do not rest inside burrows potentially infested by ticks.
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.

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