Publications

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

There were a total of 1926 results for your search.
Dascalu S (2019)

Measles epidemics in Romania: lessons for public health and future policy

Frontiers in Public Health 7,

Abstract

Measles is a highly infectious viral disease that continues to be a challenge for many countries worldwide. Although significant improvements have been observed since the introduction of vaccines, measles remains endemic in Romania. Contributing factors include vaccine hesitancy, difficulties in delivering doses to the population, and even the lack of sufficient vaccine supplies. These problems are further exacerbated by an inadequate implementation of public health measures, ranging from inefficient communication programs to the absence of a legislative framework concerning immunization. Moreover, many of the recent outbreaks were associated with chains of transmission in other countries, thus making the control of measles in Romania relevant at an international level. As many difficulties exist, understanding the key factors that limit the success of public health programs may provide guidance in shaping future strategies. Because similar issues are being faced in various other countries, the management of measles in Romania offers valuable lessons for researchers and policy-makers alike.

Bassano I, Ong S H, Sanz-Hernandez M, Vinkler M, Kebede A, Hanotte O, Onuigbo E, Fife M, Kellam P (2019)

Comparative analysis of the chicken IFITM locus by targeted genome sequencing reveals evolution of the locus and positive selection in IFITM1 and IFITM3

BMC Genomics 20, 272

Abstract

The interferon-induced transmembrane (IFITM) protein family comprises a class of restriction factors widely characterised in humans for their potent antiviral activity. Their biological activity is well documented in several animal species, but their genetic variation and biological mechanism is less well understood, particularly in avian species. Here we report the complete sequence of the domestic chicken Gallus gallus IFITM locus from a wide variety of chicken breeds to examine the detailed pattern of genetic variation of the locus on chromosome 5, including the flanking genes ATHL1 and B4GALNT4. We have generated chIFITM sequences from commercial breeds (supermarket-derived chicken breasts), indigenous chickens from Nigeria (Nsukka) and Ethiopia, European breeds and inbred chicken lines from the Pirbright Institute, totalling of 206 chickens. Through mapping of genetic variants to the latest chIFITM consensus sequence our data reveal that the chIFITM locus does not show structural variation in the locus across the populations analysed, despite spanning diverse breeds from different geographic locations. However, single nucleotide variants (SNVs) in functionally important regions of the proteins within certain groups of chickens were detected, in particular the European breeds and indigenous birds from Ethiopia and Nigeria. In addition, we also found that two out of four SNVs located in the chIFITM1 (Ser36 and Arg77) and chIFITM3 (Val103) proteins were simultaneously under positive selection. Together these data suggest that IFITM genetic variation may contribute to the capacities of different chicken populations to resist virus infection.

Lee H J, Park K J, Lee K Y, Yao Y, Nair V, Han J Y (2019)

Sequential disruption of ALV host receptor genes reveals no sharing of receptors between ALV subgroups A, B, and J

Journal of Animal Science and Biotechnology 10 (1), 23

Abstract

Previously, we showed that targeted disruption of viral receptor genes in avian leukosis virus (ALV) subgroups using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9))-based genome editing confers resistance to ALV subgroups B and J. Here, we used the same strategy to target the receptor expressed by ALV subgroup A (TVA) and generate chicken cells resistant to infection by this virus. CRISPR/Cas9-based disruption of exon 2 within the tva gene of DF-1 fibroblasts conferred resistance to infection by ALV subgroup A regardless of whether frameshift mutations were introduced during editing. Conversely, overexpression of the wild-type TVA receptor (wtTVA) by tva-modified DF-1 clones restored susceptibility to ALV subgroup A. The results confirm that exon 2, which contains the low-density lipoprotein receptor class A domain of TVA, is critical for virus entry. Furthermore, we sequentially modified DF-1 cells by editing the tva, tvb, and Na+/H+ exchange 1 (chNHE1) genes, which are the specific receptors for ALV subgroups A, B, and J, respectively. Simultaneous editing of multiple receptors to block infection by different subgroups of ALV confirmed that ALV subgroups A, B, and J do not share host receptors. This strategy could be used to generate cells resistant to multiple viral pathogens that use distinct receptors for cell entry.

Lycett S, Tanya V N, Hall M, King D P, Mazeri S, Mioulet V, Knowles N J, Wadsworth J, Bachanek-Bankowska K, Ngu Ngwa V, Morgan K L, Bronsvoort B M C (2019)

The evolution and phylodynamics of serotype A and SAT2 foot-and-mouth disease viruses in endemic regions of Africa

Scientific Reports 9, 5614

Abstract

Foot-and-mouth disease (FMD) is a major livestock disease with direct clinical impacts as well as indirect trade implications. Control through vaccination and stamping-out has successfully reduced or eradicated the disease from Europe and large parts of South America. However, sub-Saharan Africa remains endemically affected with 5/7 serotypes currently known to be circulating across the continent. This has significant implications both locally for livestock production and poverty reduction but also globally as it represents a major reservoir of viruses, which could spark new epidemics in disease free countries or vaccination zones. This paper describes the phylodynamics of serotypes A and SAT2 in Africa including recent isolates from Cameroon in Central Africa. We estimated the most recent common ancestor for serotype A was an East African virus from the 1930s (median 1937; HPD 1922-1950) compared to SAT2 which has a much older common ancestor from the early 1700s (median 1709; HPD 1502-1814). Detailed analysis of the different clades shows clearly that different clades are evolving and diffusing across the landscape at different rates with both serotypes having a particularly recent clade that is evolving and spreading more rapidly than other clades within their serotype. However, the lack of detailed sequence data available for Africa seriously limits our understanding of FMD epidemiology across the continent. A comprehensive view of the evolutionary history and dynamics of FMD viruses is essential to understand many basic epidemiological aspects of FMD in Africa such as the scale of persistence and the role of wildlife and thus the opportunities and scale at which vaccination and other controls could be applied. Finally we ask endemic countries to join the OIE/FAO supported regional networks and take advantage of new cheap technologies being rolled out to collect isolates and submit them to the World Reference Laboratory.

Everett H E, Aramouni M, Coward V, Ramsay A, Kelly M, Morgan S, Tchilian E, Canini L, Woolhouse M E J, Gilbert S, Charleston B, Brown I H, Brookes S M (2019)

Vaccine-mediated protection of pigs against infection with pandemic H1N1 2009 swine influenza A virus requires a close antigenic match between the vaccine antigen and challenge virus

Vaccine 37 (17), 2288-2293

Abstract

Swine influenza A virus (SwIV) infection has considerable economic and animal welfare consequences and, because of the zoonotic potential, can also have public health implications. The 2009 pandemic H1N1 ‘swine-origin’ infection is now endemic in both pigs and humans. In Europe, avian-like H1avN1, human-like H1huN2, human-like swine H3N2 and, since 2009, pandemic H1N1 (pH1N1) lineage viruses and reassortants, constitute the dominant subtypes. In this study, we used a swine pH1N1 challenge virus to investigate the efficacy of whole inactivated virus vaccines homologous or heterologous to the challenge virus as well as a commercial vaccine. We found that vaccine-mediated protection was most effective when vaccine antigen and challenge virus were homologous and correlated with the specific production of neutralising antibodies and a cellular response to the challenge virus. We conclude that a conventional whole inactivated SwIV vaccine must be antigenically matched to the challenge strain to be an effective control measure.

Goldeck D, Perry D M, Hayes J W P, Johnson L P M, Young J E, Roychoudhury P, McLuskey E L, Moffat K, Bakker A Q, Kwakkenbos M J, Frossard J-P, Rowland R R R, Murtaugh M P, Graham S P (2019)

Establishment of systems to enable isolation of porcine monoclonal antibodies broadly neutralizing the porcine reproductive and respiratory syndrome virus

Frontiers in Immunology 10, 572

Abstract

The rapid evolution of porcine reproductive and respiratory syndrome viruses (PRRSV) poses a major challenge to effective disease control since available vaccines show variable efficacy against divergent strains. Knowledge of the antigenic targets of virus-neutralizing antibodies that confer protection against heterologous PRRSV strains would be a catalyst for the development of next-generation vaccines. Key to discovering these epitopes is the isolation of neutralizing monoclonal antibodies (mAbs) from immune pigs. To address this need, we sought to establish systems to enable the isolation of PRRSV neutralizing porcine mAbs. We experimentally produced a cohort of immune pigs by sequential challenge infection with four heterologous PRRSV strains spanning PRRSV-1 subtypes and PRRSV species. Whilst priming with PRRSV-1 subtype 1 did not confer full protection against a subsequent infection with a PRRSV-1 subtype 3 strain, animals were protected against a subsequent PRRSV-2 infection. The infection protocol resulted in high serum neutralizing antibody titers against PRRSV-1 Olot/91 and significant neutralization of heterologous PRRSV-1/-2 strains. Enriched memory B cells isolated at the termination of the study were genetically programmed by transduction with a retroviral vector expressing the Bcl-6 transcription factor and the anti-apoptotic Bcl-xL protein, a technology we demonstrated efficiently converts porcine memory B cells into proliferating antibody-secreting cells. Pools of transduced memory B cells were cultured and supernatants containing PRRSV-specific antibodies identified by flow cytometric staining of infected MARC-145 cells and in vitro neutralization of PRRSV-1. Collectively, these data suggest that this experimental system may be further exploited to produce a panel of PRRSV-specific mAbs, which will contribute both to our understanding of the antibody response to PRRSV and allow epitopes to be resolved that may ultimately guide the design of immunogens to induce cross-protective immunity.

Guzman E, Pujol M E, Ribeca P, Montoya M (2019)

Bovine derived in vitro cultures generate heterogeneous populations of antigen presenting cells

Frontiers in Immunology 10, 612

Abstract

Antigen presenting cells (APC) of the mononuclear phagocytic system include dendritic cells (DCs) and macrophages (Macs) which are essential mediators of innate and adaptive immune responses. Many of the biological functions attributed to these cell subsets have been elucidated using models that utilize in vitro-matured cells derived from common progenitors. However, it has recently been shown that monocyte culture systems generate heterogeneous populations of cells, DCs and Macs. In light of these findings, we analysed the most commonly used bovine in vitro-derived APC models and compared them to bona fide DCs and Macs. Here, we show that bovine monocyte-derived DCs and Macs can be differentiated on the basis of CD11c and MHC class II (MHCII) expression and that in vitro conditions generate a heterologous group of both DCs and Macs with defined and specific biological activities. In addition, skin-migrating macrophages present in the bovine afferent lymph were identified and phenotyped for the first time. RNA sequencing analyses showed that these monophagocytic cells have distinct transcriptomic profiles similar to those described in other species. These results have important implications for the interpretation of data obtained using in vitro systems. 

Mulumba-Mfumu L K, Saegerman C, Dixon L K, Madimba K C, Kazadi E, Mukalakata N T, Oura C A L, Chenais E, Masembe C, Stahl K, Thiry E, Penrith M L (2019)

African swine fever: update on Eastern, Central and Southern Africa

Transboundary and Emerging Diseases 66 (4), 1462-1480
Publisher’s version: https://doi.org/10.1111/tbed.13187

Abstract

Control of African swine fever (ASF) in countries in Eastern, Central and Southern Africa (ECSA) is particularly complex owing to the presence of all three known epidemiological cycles of maintenance of the virus, namely an ancient sylvatic cycle involving the natural hosts and vectors of the disease as well as domestic cycles with and without involvement of natural vectors. While the situation is well documented in some of the countries, for others very little information is available. In spite of the unfavourable ASF situation, the pig population in the sub-region has grown exponentially in recent decades and is likely to continue to grow in response to rapid urban growth resulting in increasing demand for animal protein by populations that are no longer engaged in livestock production. Better management of ASF will be essential to permit the pig sector to reach its full potential as a supplier of high quality protein and a source of income to improve livelihoods and create wealth. No vaccine is currently available and it is likely that, for the near future, the sub-region will continue to rely on the implementation of preventive measures, based on the epidemiology of the disease, to avoid both the devastating losses that outbreaks can cause and the risk the sub-region poses to other parts of Africa and the world. The current situation in the ECSA sub-region is reviewed and gaps in knowledge are identified in order to support ongoing strategy development for managing ASF in endemic areas. This article is protected by copyright. All rights reserved.

Bataille A, Kwiatek O, Belfkhi S, Mounier L, Parida S, Mahapatra M, Caron A, Chubwa C C, Keyyu J, Kock R, Jones B A, Libeau G (2019)

Optimization and evaluation of a non-invasive tool for peste des petits ruminants surveillance and control

Scientific Reports 9 (1), 4742

Abstract

Peste des petits ruminants (PPR) is a highly contagious and devastating viral disease affecting mainly sheep and goats, but also a large number of wild species within the order Artiodactyla. A better understanding of PPR transmission dynamics in multi-host systems is necessary to efficiently control the disease, in particular where wildlife and livestock co-occur. Notably, the role of wildlife in PPR epidemiology is still not clearly understood. Non-invasive strategies to detect PPR infection without the need for animal handling could greatly facilitate research on PPR epidemiology and management of the disease in atypical hosts and in complex field situations. Here, we describe optimized methods for the direct detection of PPR virus genetic material and antigen in fecal samples. We use these methods to determine the detection window of PPR in fecal samples, and compare the sensitivity of these methods to standard invasive sampling and PPR diagnostic methods using field samples collected at a wildlife-livestock interface in Africa. Our results show that quantitative reverse transcription PCR (RT-QPCR) amplification of PPRV from fecal swabs has good sensitivity in comparison to ocular swabs. Animals infected by PPRV could be identified relatively early on and during the whole course of infection based on fecal samples using RT-QPCR. Partial gene sequences could also be retrieved in some cases, from both fecal and ocular samples, providing important information about virus origin and relatedness to other PPRV strains. Non-invasive strategies for PPRV surveillance could provide important data to fill major gaps in our knowledge of the multi-host PPR epidemiology.

Parida S, Selvaraj M, Gubbins S, Pope R, Banyard A, Mahapatra M (2019)

Quantifying levels of peste des petits ruminants (PPR) virus in excretions from experimentally infected goats and its importance for nascent PPR eradication programme

Viruses 11 (3), 249
Publisher’s version: https://doi.org/10.3390/v11030249

Abstract

Following the successful eradication of rinderpest, the World Organization of Animal Health (OIE) and the Food and Agriculture Organisation (FAO) have set a goal to globally eradicate Peste des petits ruminants (PPR) by 2030. To support the eradication programme we have quantified the levels of PPR virus (PPRV) nucleic acid excreted in body fluids (blood, feces, saliva, nasal and eye swabs) of PPRV-infected goats to ascertain which days post-infection animals are potentially infectious, and hence direct quarantine activities. The data will also indicate optimal sample strategies to assess presence of PPR infection in the naturally infected herd. Peak PPRV nucleic acid detection in different bodily fluids was between 5 and 10 days post-infection. As such, this period must be considered the most infectious period for contact transmission, although high viral load was observed through RNA detection in nasal excretions from two days post-infection until at least two weeks post-infection. Percentage sample positivity was low both in eye swabs and saliva samples during the early stage of infection although RNA was detected as late as two weeks post-infection. From the individual animal data, PPRV was detected later post-infection in fecal material than in other body fluids and the detection was intermittent. The results from this study indicate that nasal swabs are the most appropriate to sample when considering molecular diagnosis of PPRV.

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