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

The emergence of a previously unrecognized route of Bacillus anthracis infection over the last few years has led to concern: sporadic anthrax outbreaks among heroin users in northern Europe have demonstrated the severe pathology associated with the newly described ‘injectional anthrax’. With a high case fatality rate and non-specific early symptoms, this is a novel clinical manifestation of an old disease. Lack of awareness of this syndrome among emergency room clinicians can lead to a delayed diagnosis among heroin users; indeed, for many health workers in developed countries, where infection by B. anthracis is rare, this may be the first time they have encountered anthrax infections. As the putative route of contamination of the heroin supply is potentially ongoing, it is important that clinicians and public health workers remain vigilant for early signs of injectional anthrax.
Attoui H, Mohd Jaafar F (2015)

Zoonotic and emerging orbivirus infections

Revue Scientifique et Technique 34 (2), 353-361

Abstract

Many novel emerging orbiviruses have been isolated in the past 15 years. Important viruses include Peruvian horse sickness virus (PHSV) and Yunnan orbivirus (YUOV), pathogens of equids which were originally isolated almost simultaneously from 1997 to 1999 in the People's Republic of China, Australia and Peru. YUOV has also been isolated from cattle, sheep and a dog. The isolation of YUOV from a dog is not the first case of an orbivirus being isolated from a carnivore. Bluetongue virus and African horse sickness virus were earlier detected in carnivores which fed on contaminated meat. PHSV and YUOV both offer an opportunity to study the emergence of a single pathogen in geographically distant locations, although the original point of emergence is still unidentified. PHSV has been isolated form horses with neurological disease both in Australia and in Peru (where it is now endemic). Serological and molecular diagnostic assays have been developed for these viruses to assist in their identification and diagnosis. Other orbiviruses, such as Palyam virus and equine encephalosis virus, have more recently been identified outside their geographical boundaries and may represent a threat to domesticated livestock and horses, respectively. The article also reviews four zoonotic orbivirus species (Corriparta virus, Changuinola virus, Kemerovo virus and Orungo virus) which have been identified in livestock and/or wildlife.

Abstract

Tudor staphylococcal nuclease (Tudor-SN) and Argonaute (Ago) are conserved components of the basic RNA interference (RNAi) machinery with a variety of functions including immune response and gene regulation. The RNAi machinery has been characterized in tick vectors of human and animal diseases but information is not available on the role of Tudor-SN in tick RNAi and other cellular processes. Our hypothesis is that tick Tudor-SN is part of the RNAi machinery and may be involved in innate immune response and other cellular processes. To address this hypothesis, Ixodes scapularis and I. ricinus ticks and/or cell lines were used to annotate and characterize the role of Tudor-SN in dsRNA-mediated RNAi, immune response to infection with the rickettsia Anaplasma phagocytophilum and the flaviviruses TBEV or LGTV and tick feeding. The results showed that Tudor-SN is conserved in ticks and involved in dsRNA-mediated RNAi and tick feeding but not in defense against infection with the examined viral and rickettsial pathogens. The effect of Tudor-SN gene knockdown on tick feeding could be due to down-regulation of genes that are required for protein processing and blood digestion through a mechanism that may involve selective degradation of dsRNAs enriched in G:U pairs that form as a result of adenosine-to-inosine RNA editing. These results demonstrated that Tudor-SN plays a role in tick RNAi pathway and feeding but no strong evidence for a role in innate immune responses to pathogen infection was found.

Abstract

BACKGROUND: Biting midges of the genus Culicoides Latreille, 1809 (Diptera: Ceratopogonidae) cause a significant biting nuisance to equines and are responsible for the biological transmission of African horse sickness virus (AHSV). While currently restricted in distribution to sub-Saharan Africa, AHSV has a history of emergence into southern Europe and causes one of the most lethal diseases of horses and other species of Equidae. In the event of an outbreak of AHSV, the use of insecticide treated nets (ITNs) to screen equine accomodation is recommended by competent authorities including the Office International des Epizooties (OIE) in order to reduce vector-host contact. METHODS: Seven commercially avaliable pyrethroid insecticides and three repellent compounds, all of which are licensed for amateur use, were assessed in modified World Health Organization (WHO) cone bioassay trials in the laboratory using a colony line of Culicoides nubeculosus (Meigen), 1830. Two field trials were subsequently conducted to test the efficiency of treated net screens in preventing entry of Culicoides. RESULTS: A formulation of cypermethrin (0.15% w/w) and pyrethrins (0.2% w/w) (Tri-Tec 14(R), LS Sales (Farnham) Ltd, Bloxham, UK) applied to black polyvinyl-coated polyester insect screen (1.6mm aperture; 1.6mm thickness) inflicted 100% mortality on batches of C. nubeculosus following a three minute exposure in the WHO cone bioassays at 1, 7 and 14days post-treatment. Tri-Tec 14(R) outperformed all other treatments tested and was subsequently selected for use in field trials. The first trial demonstrated that treated screens placed around an ultraviolet light-suction trap entirely prevented Culicoides being collected, despite their collection in identical traps with untreated screening or no screening. The second field trial examined entry of Culicoides into stables containing horses and found that while the insecticide treated screens reduced entry substantially, there was still a small risk of exposure to biting. CONCLUSIONS: Screened stables can be utilised as part of an integrated control program in the event of an AHSV outbreak in order to reduce vector-host contact and may also be applicable to protection of horses from Culicoides during transport.
Banyard A C, Parida S (2015)

Molecular epidemiology of peste des petits ruminants virus

Peste des Petits Ruminants Virus (edited by M Munir, Springer), 69-93

Abstract

Peste des petits ruminants virus (PPRV) causes an economically important plague of small ruminants. The virus is endemic across much of the developing world and has even spread into the developed world through the spread of the infection into sheep and goat populations within European Turkey. Where the virus is present, it is often seen to disproportionately affect small ruminant production, often causing increased poverty in what are already the poorest areas of the globe. PPR is considered to be a transboundary disease of great significance through its effect on the development and maintenance of sustainable agriculture in developing countries, most notably in Western Africa and South Asia. Here, we review reporting to the World Organization for Animal Health (OIE) and World Reference Laboratories (WRLs) over the last 16 years and comment on reporting systems. Furthermore, we discuss the utility of molecular tools to genetically type PPRV infection across Africa, Asia and Europe.

Abstract

Epitopes on the surface of the foot-and-mouth disease virus (FMDV) capsid have been identified by monoclonal antibody (mAb) escape mutant studies leading to the designation of four antigenic sites in serotype A FMDV. Previous work focused on viruses isolated mainly from Asia, Europe and Latin America. In this study we report on the prediction of epitopes in African serotype A FMDVs and testing of selected epitopes using reverse genetics. Twenty-four capsid amino acid residues were predicted to be of antigenic significance by analysing the capsid sequences (n?=?56) using in silico methods, and six residues by correlating capsid sequence with serum–virus neutralization data. The predicted residues were distributed on the surface-exposed capsid regions, VP1–VP3. The significance of residue changes at eight of the predicted epitopes was tested by site-directed mutagenesis using a cDNA clone resulting in the generation of 12 mutant viruses involving seven sites. The effect of the amino acid substitutions on the antigenic nature of the virus was assessed by virus neutralization (VN) test. Mutations at four different positions, namely VP1-43, VP1-45, VP2-191 and VP3-132, led to significant reduction in VN titre (P value?=?0.05, 0.05, 0.001 and 0.05, respectively). This is the first time, to our knowledge, that the antigenic regions encompassing amino acids VP1-43 to -45 (equivalent to antigenic site 3 in serotype O), VP2-191 and VP3-132 have been predicted as epitopes and evaluated serologically for serotype A FMDVs. This identifies novel capsid epitopes of recently circulating serotype A FMDVs in East Africa.

Abstract

Early responses against viruses, such as avian influenza virus (AIV), may be induced by Toll-like receptor (TLR) pathways. In the present study, an in ovo model was employed to study the antiviral activities of TLR ligands. It was hypothesized that administration of TLR ligands in ovo at the appropriate dose and time can reduce AIV titer in embryonated chicken eggs. Moreover, the study aimed to determine the mechanisms involved in the TLR-mediated antiviral responses in the chorioallantoic membrane (CAM). Embryonated eggs (10-14 day old) were treated with TLR2, 4, 7, and 21 ligands using different doses and times pre- and post-AIV infection. The results revealed that treatment of embryonated chicken eggs with TLR ligands reduced AIV replication. Further analysis showed that TLR ligands induced interferon (IFN)-gamma and IFN stimulatory genes in the CAM, which may have played a role in the reduction of the AIV titer. The timing and dose of TLR ligands administration had significant impacts on the outcome of the treated eggs. In conclusion, the present study demonstrated that the in ovo route may be employed to determine the antiviral characteristics of TLR ligands against AIV.

Abstract

To rapidly return to trade, countries with OIE status, FMD-free country where vaccination is not practised, have destroyed emergency vaccinated animals, raising ethical concerns with respect to social values, the environment, animal welfare and global food security. This two-part review explores whether science could support eligibility to return to previous OIE status in 3 months irrespective of vaccinate-to-live or vaccinate-to-die policies. Here, we examine the benefits of higher potency (>/= 6 PD50 ), high-purity vaccines formulated from antigen banks for emergency use, their efficacy and performance in differentiating infected from vaccinated animals (DIVA) assays for post-outbreak surveillance. From an intensive programme of research, we conclude that high-quality, higher potency vaccines are proven to reduce FMD virus (FMDV) subclinical circulation and the risk of carriers. Broader coverage than predicted by serology suggests the potential to hold a few 'key' vaccine strains improving logistics and reducing the financial burden of antigen banks. The OIE should adopt formal definitions for emergency vaccination and emergency vaccines. In terms of supportive tools, we consider that the lack of OIE recognition of DIVA tests other than those of PANAFTOSA in cattle is a shortcoming. There is need for research on maternal antibody interference with DIVA tests and on the use of such tests to establish whether greater purification of vaccines improves performance. We consider that alignment of waiting periods for vaccinate-to-live and vaccinate-to-die in OIE Code Article 8.5.9 1 b. and c. is feasible until an acceptable level of statistical certainty for surveillance or target probability of freedom is established to substantiate the absence of FMDV infection or circulation. It is surveillance intensity rather than waiting periods that establishes the risk of residual FMDV. EU Directive 2003/85/EC implicitly recognizes this, permitting derogation of the OIE waiting periods.

Abstract

Peste des petits ruminants (PPR) is a viral disease of sheep and goats that is spreading through many countries in the developing world. Work on the virus is often restricted to studies of attenuated vaccine strains or to work in laboratories that have high containment facilities. We have created a helper cell dependent form of PPR virus by removing the entire RNA polymerase gene and complementing it with polymerase made constitutively in a cell line. The resultant L-deleted virus grows efficiently in the L-expressing cell line but not in other cells. Virus made with this system is indistinguishable from normal virus when used in diagnostic assays, and can be grown in normal facilities without the need for high level biocontainment. The L-deleted virus will thus make a positive contribution to the control and study of this important disease.
Baron M D, Holzer B (2015)

Nairobi sheep disease virus /Ganjam virus

Revue Scientifique et Technique 34 (2), 411-417

Abstract

Nairobi sheep disease virus (NSDV) is a tick-borne virus which causes a severe disease in sheep and goats, and has been responsible for several outbreaks of disease in East Africa. The virus is also found in the Indian subcontinent, where it is known as Ganjam virus. The virus only spreads through the feeding of competent infected ticks, and it is therefore limited in its geographic distribution by the distribution of those ticks, Rhipicephalus appendiculata in Africa and Haemaphysalis intermedia in India. Animals bred in endemic areas d not normally develop disease, and the impact is therefore primarily on animals being moved for trade or breeding purposes. The disease caused by NSDV has similarities to several other ruminant diseases, and laboratory diagnosis is necessary for confirmation. There are published methods for diagnosis based on polymerase chain reaction, for virus growth in cell culture and for other simple diagnostic tests, though none has been commercialised. There is no established vaccine against NSDV, although cell-culture attenuated strains have been developed which show promise and could be put into field trials if it were deemed necessary. The virus is closely related to Crimean-Congo haemorrhagic fever virus, and studies on NSDV may therefore be useful in understanding this important human pathogen.

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