Publications

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

There were a total of 2026 results for your search.

Abstract

Increasing access to next-generation sequencing (NGS) technologies is revolutionizing the life sciences. In disease ecology, NGS-based methods have the potential to provide higher-resolution data on communities of parasites found in individual hosts as well as host populations. Here, we demonstrate how a novel analytical method, utilizing high-throughput sequencing of PCR amplicons, can be used to explore variation in blood-borne parasite (Theileria—Apicomplexa: Piroplasmida) communities of African buffalo at higher resolutions than has been obtained with conventional molecular tools. Results reveal temporal patterns of synchronized and opposite fluctuations of prevalence and relative abundance of Theileria spp. within the host population, suggesting heterogeneous transmission across taxa. Furthermore, we show that the community composition of Theileria spp. and their subtypes varies considerably between buffalo, with differences in composition reflected in mean and variance of overall parasitemia, thereby showing potential to elucidate previously unexplained contrasts in infection outcomes for host individuals. Importantly, our methods are generalizable as they can be utilized to describe blood-borne parasite communities in any host species. Furthermore, our methodological framework can be adapted to any parasite system given the appropriate genetic marker. The findings of this study demonstrate how a novel NGS-based analytical approach can provide fine-scale, quantitative data, unlocking opportunities for discovery in disease ecology.

Pruvot M, Fine A E, Hollinger C, Strindberg S, Damdinjav B, Buuveibaatar B, Chimeddorj B, Bayandonoi G, Khishgee B, Sandag B, Narmandakh J, Jargalsaikhan T, Bataa B, McAloose D, Shatar M, Basan G, Mahapatra M, Selvaraj M, Parida S, Njeumi F, Kock R, Shiilegdamba E (2020)

Outbreak of peste des petits ruminants among critically endangered mongolian saiga and other wild ungulates, Mongolia, 2016-2017

Emerging Infectious Diseases 26 (1), 51-62

Abstract

The 2016-2017 introduction of peste des petits ruminants virus (PPRV) into livestock in Mongolia was followed by mass mortality of the critically endangered Mongolian saiga antelope and other rare wild ungulates. To assess the nature and population effects of this outbreak among wild ungulates, we collected clinical, histopathologic, epidemiologic, and ecological evidence. Molecular characterization confirmed that the causative agent was PPRV lineage IV. The spatiotemporal patterns of cases among wildlife were similar to those among livestock affected by the PPRV outbreak, suggesting spillover of virus from livestock at multiple locations and time points and subsequent spread among wild ungulates. Estimates of saiga abundance suggested a population decline of 80%, raising substantial concerns for the species' survival. Consideration of the entire ungulate community (wild and domestic) is essential for elucidating the epidemiology of PPRV in Mongolia, addressing the threats to wild ungulate conservation, and achieving global PPRV eradication.

Abstract

RNA viruses exist as populations of closely related genomes, characterized by a high diversity of low-frequency variants. As viral genomes from one population disperse to establish new sites of replication, the fate of these low-frequency variants depends to a large extent on the size of the founding population. Focusing on foot-and-mouth disease virus (FMDV) we conjecture that variants are more likely to be transmitted through wide bottlenecks, but more likely to approach fixation in new populations following narrow bottlenecks; therefore, the longer-term rate of accumulation of 'nearly neutral' variants at high frequencies is likely to be inversely related to the bottleneck size. We examine this conjecture in vivo by estimating bottleneck sizes relating 'parent' and 'daughter' populations observed at different scales ranging from within host to between host (within the same herd, and in different herds) using a previously established method. Within hosts, we find bottleneck sizes to range from 5 to 20 viral genomes between populations transmitted from the pharynx to the serum, and from 4 to 54 between serum and lesion populations. Between hosts, we find bottleneck sizes to range from 2 to 39, suggesting inter-host bottlenecks are of a similar size to intra-host bottlenecks. We establish a statistically significant negative relationship between the probability of genomic consensus level change and bottleneck size, and present a simple sampling model that captures this empirical relationship. We also present a novel in vitro experiment to investigate the impact of bottleneck size on the frequency of mutations within FMDV populations, demonstrate that variant frequency in a population increases more rapidly during small population passages, and provide evidence for positive selection during the passage of large populations.

Abstract

There are 7 serotypes of Foot-and-Mouth Disease Virus and multiple strains of each serotype. The emergence of new strains can result in widespread outbreaks of disease and requires new vaccines to be developed. The major mechanisms driving variation are thought to be substitutions in the viral genome. Recombination in the capsid-coding region of the virus genome has been described at phylogenetic scales but not thought to play a major role in generating variants. In the current experiment, a co-infection of African buffaloes with closely related sub-populations of viruses allowed us to detect recombination events. For structural protein-coding sequences, the genetic composition of the population is driven by extensive within-host recombination. During the acute infection phase the intra-host recombination rates of 0.1 per base per year are comparable to the typical mutation rates of the virus. The recombination map reveals two strongly linked regions within the VP1 protein-coding sequence. Epistatic interactions between co-evolved mutations in VP1 are caused by intra-host selection at the RNA and protein level and are present both within and between the two regions. Our findings in this experimental setting support a major role for recombination and epistasis in the intra-host evolution of FMDV.

Abstract

Recent data suggest that porcine gammadelta T cells exhibit a similar degree of functional plasticity as human and murine gammadelta T cells. Due to the high frequency of TCR-gammadelta+ cells in blood and secondary lymphatic organs, the pig is an attractive model to study these cells, especially their combined features of the innate and the adaptive immune system. Using a 5' RACE-like approach, we translated a human/murine NGS library preparation strategy to capture full-length V-(D)-J TRG and TRD clonotypes in swine. After oligo(dT) primed conversion of input RNA, the cDNA population was enriched for full-length V(D)J TCR transcripts with porcine-specific primers including Illumina adaptor sequences as overhangs for Illumina MiSeq analysis. After quality control and processing by FastQC and ea-utils, porcine TRG and TRD sequences were mapped against the human IMGT reference directory. Porcine blood-derived CD2+ and CD2- TCR-gammadelta+ cells exhibited two distinct clonotypes Vgamma11JgammaP1 (74.6%) and Vgamma10JgammaP1 (57.7%), respectively. Despite the high TCR-delta diversity among CD2+ cells (39 clonotypes), both subsets shared the same abundant Vdelta1DdeltaxJdelta4 clonotype at approximately identically frequencies (CD2+: 31.2%; CD2- : 37.0%). The flexible nature of this approach will facilitate the assessment of organ-specific phenotypes of gammadelta T cell subsets alongside with their respective TCR diversity at single cell resolution.                       

Siddell S G, Walker P J, Lefkowitz E J, Mushegian A R, Dutilh B E, Harrach B, Harrison R L, Junglen S, Knowles N J, Kropinski A M, Krupovic M, Kuhn J H, Nibert M L, Rubino L, Sabanadzovic S, Simmonds P, Varsani A, Zerbini F M, Davison A J (2020)

Binomial nomenclature for virus species: a consultation

Archives of Virology 165 (2), 519-525

Abstract

The Executive Committee of the International Committee on Taxonomy of Viruses (ICTV) recognizes the need for a standardized nomenclature for virus species. This article sets out the case for establishing a binomial nomenclature and presents the advantages and disadvantages of different naming formats. The Executive Committee understands that adopting a binomial system would have major practical consequences, and invites comments from the virology community before making any decisions to change the existing nomenclature. The Executive Committee will take account of these comments in deciding whether to approve a standardized binomial system at its next meeting in October 2020. Note that this system would relate only to the formal names of virus species and not to the names of viruses.

Abstract

The Killer-cell Immunoglobulin-like Receptors (KIR) are encoded by a diverse group of genes, which are characterized by allelic polymorphism, gene duplications, and recombinations, which may generate recombinant entities. The number of reported macaque KIR sequences is steadily increasing, and these data illustrate a gene system that may match or exceed the complexity of the human KIR cluster. This report lists the names of quality controlled and annotated KIR genes/alleles with all the relevant references for two different macaque species: rhesus and cynomolgus macaques. Numerous recombinant KIR genes in these species necessitate a revision of some of the earlier-published nomenclature guidelines. In addition, this report summarizes the latest information on the Immuno Polymorphism Database (IPD)-NHKIR Database, which contains annotated KIR sequences from four non-human primate species.

Abstract

Vaccination is the main tool for control of peste des petits ruminants (PPR) because of the availability of effective and safe vaccines that provide long lasting protection. However vaccination campaigns may not always provide sufficient herd immunity needed to prevent disease outbreaks because of logistic problems with vaccination such as inappropriate cold chain and vaccine delivery methods, and the rapid population turnover of small ruminants. This study was carried out to assess post-vaccination herd immunity against PPR and inter-vaccination population turnover in small ruminant flocks in Metema district, northwest Ethiopia where frequent PPR outbreaks occur despite regular vaccination. A total of 412 serum samples were collected from selected small ruminants in 72 flocks (average flock size of 33.4 and standard deviation of 30) above three months of age in three kebeles immediately before a vaccination program. One month after the vaccination using freeze dried live attenuated vaccine, 359 serum samples were collected from randomly selected small ruminants in the same flocks. The collected serum samples were analyzed to determine the seropositivity using a monoclonal antibody-based C-ELISA. The pre-vaccination seropositivity of 72.3% (95% CI: 67.8-76.4) increased to 93.9% (95% CI: 90.9-95.9) post-vaccination (P<0.001). The observed seropositivity following vaccination was above the recommended herd immunity threshold (80%) required to reduce the transmission of infection in the population sufficient to eliminate virus. A survey of sampled flocks six months post-sampling indicated only 68% of animals were still present in these flocks. This population turnover reduces the herd immunity to about 64% which is below the required threshold for control. The high level of herd immunity achieved post-vaccination indicates good vaccine quality, cold chain maintenance and effective vaccine delivery in the district's vaccination campaigns. The decrease in herd immunity associated with population turnover and annual vaccination intervals represents a challenge to effective control and suggests changes to the timing or frequency of the vaccination is required.

Willems T, De Vleeschauwer A, Perez-Filgueira M, Li Y, Ludi A, Lefebvre D, Wilsden G, Statham B, Haas B, Mattion N, Robiolo B, Beascoechea Perez C, Maradei E, Smitsaart E, La Torre J, De Clercq K (2020)

FMD vaccine matching: inter laboratory study for improved understanding of r1 values

Journal of Virological Methods 276, 113786

Abstract

Foot-and-mouth disease virus (FMDV) is a highly variable RNA virus existing as seven different serotypes. The antigenic variability between and within serotypes can limit the cross-reactivity and therefore the in vivo cross-protection of vaccines. Selection of appropriate vaccine strains is crucial in the control of FMD. Determination of indirect relationships (r1-value) between potential vaccine strains and field strains based on antibody responses against both are routinely used for vaccine matching purposes. Aiming at the investigation of the repeatability, reproducibility and comparability of r1-value determination within and between laboratories and serological tests, a small scale vaccine matching ring test for FMDV serotype A was organized. Well-characterized serum pools from cattle vaccinated with a monovalent A24/Cruzeiro/Brazil/55 (A24) FMD vaccine with known in vivo protection status (homologous and heterologous) were distributed to four laboratories to determine r1-values for the heterologous FMD strains A81/Argentina/87, A/Argentina/2000 and A/Argentina/2001 using the virus neutralization tests (VNT) and liquid phase blocking ELISA (LPBE). Within laboratories, the repeatability of r1-value determination was high for both antibody assays. VNT resulted in reproducible and comparable r1-values between laboratories, indicative of a lack of antigenic relatedness between the A24 strain and the heterologous strains tested in this work, thus corresponding to some of the in vivo findings with these strains. Using LPBE, similar trends in r1-values were observed in all laboratories, but the overall reproducibility was lower than with VNT. Inconsistencies between laboratories may at least in part be attributed to differences in LPBE protocols as well as the in preexisting information generated in each laboratory (such as antibody titer-protection correlation curves). To gain more insight in the LPBE-derived r1-values standard bovine control sera were included in the antibody assays performed in each laboratory and a standardization exercise was performed.

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