Publications

Publications

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

There were a total of 1487 results for your search.
Hamilton C A, Mahan S, Bell C R, Villarreal-Ramos B, Charleston B, Entrican G, Hope J C (2017)

Frequency and phenotype of NK cells and NK cell subsets in bovine lymphoid compartments and blood

Immunology early view,

Abstract

NK cells are widely distributed in lymphoid and non-lymphoid tissues however little is known about the recirculation of NK cells between blood and tissues. This is relevant to understanding recirculation in the steady-state and also for determining the roles for NK cells in vaccine-induced immunity and responses to infection. Therefore, the percentage of NK cells and their phenotype across peripheral blood, afferent lymph and lymph nodes in steady-state conditions was investigated in cattle using the pseudo-afferent lymphatic cannulation model. CD2+ CD25lo NK cells were the predominant subset of NK cells within the blood. In contrast, CD2- CD25hi NK cells were the main subset present within the skin-draining afferent lymphatic vessels and lymph nodes, indicating that CD2- NK cells are the principal NK cell subset trafficking to LNs via the afferent lymphatic vessel. Furthermore, a low percentage of NK cells were present in efferent lymph which were predominantly of the CD2- subset indicating that NK cells can egress from lymph nodes and return to circulation in steady-state conditions. These compartmentalisation data indicate that NK cells represent a population of recirculating lymphocytes in steady-state conditions and therefore may be important during immune responses to vaccination or infection.

Zhang B, Chen L, Silacci C, Thom M, Boyington J C, Druz A, Joyce M G, Guzman E, Kong W-P, Lai Y-T, Stewart-Jones G B E, Tsybovsky Y, Yang Y, Zhou T, Baxa U, Mascola J R, Corti D, Lanzavecchia A, Taylor G, Kwong P D (2017)

Protection of calves by a prefusion-stabilized bovine RSV F vaccine

npj Vaccines 2 (1), 7

Abstract

Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated assessment of these vaccine candidates. Here, we use a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context. A “DS2” version of bovine respiratory syncytial virus F with subunits covalently fused, fusion peptide removed, and pre-fusion conformation stabilized by cavity-filling mutations and intra- and inter-protomer disulfides was recognized by pre-fusion-specific antibodies, AM14, D25, and MPE8, and elicited bovine respiratory syncytial virus-neutralizing titers in calves >100-fold higher than those elicited by post-fusion F. When challenged with a heterologous bovine respiratory syncytial virus, virus was not detected in nasal secretions nor in respiratory tract samples of DS2-immunized calves; by contrast bovine respiratory syncytial virus was detected in all post-fusion- and placebo-immunized calves. Our results demonstrate proof-of-concept that DS2-stabilized RSV F immunogens can induce highly protective immunity from RSV in a native host with implications for the efficacy of prefusion-stabilized F vaccines in humans and for the prevention of bovine respiratory syncytial virus in calves.

Wilson A J, Morgan E R, Booth M, Norman R, Perkins S E, Hauffe H C, Mideo N, Antonovics J, McCallum H, Fenton A (2017)

What is a vector?

Philosophical Transaction of the Royal Society B 372 (1719), 2016.0085

Abstract

Many important and rapidly emerging pathogens of humans, livestock and wildlife are ‘vector-borne’. However, the term ‘vector’ has been applied to diverse agents in a broad range of epidemiological systems. In this perspective, we briefly review some common definitions, identify the strengths and weaknesses of each and consider the functional differences between vectors and other hosts from a range of ecological, evolutionary and public health perspectives. We then consider how the use of designations can afford insights into our understanding of epidemiological and evolutionary processes that are not otherwise apparent. We conclude that from a medical and veterinary perspective, a combination of the ‘haematophagous arthropod’ and ‘mobility’ definitions is most useful because it offers important insights into contact structure and control and emphasizes the opportunities for pathogen shifts among taxonomically similar species with similar feeding modes and internal environments. From a population dynamics and evolutionary perspective, we suggest that a combination of the ‘micropredator’ and ‘sequential’ definition is most appropriate because it captures the key aspects of transmission biology and fitness consequences for the pathogen and vector itself. However, we explicitly recognize that the value of a definition always depends on the research question under study.

Wang Y, Duan Y, Han C, Yao S, Qi X, Gao Y, Maier H J, Britton P, Chen L, Zhang L, Gao L, Gao H, Shen N, Wang J, Wang X (2017)

Infectious bursal disease virus subverts autophagic vacuoles to promote viral maturation and release

Journal of Virology 91 (5), e01883-16

Abstract

Autophagy functions as an intrinsic antiviral defence. However, some viruses can subvert or even enhance host autophagic machinery to increase viral replication and pathogenesis. The role of autophagy during Avibirnavirus infection, especially late stage infection, remains unclear. In this study, infectious bursal disease virus (IBDV) was used to investigate the role of autophagy in Avibirnavirus replication. We demonstrated IBDV induction of autophagy as a significant increase in puncta of LC3+ autophagosomes, endogenous levels of LC3-II, and ultrastructural characteristics typical of autophagosomes during the late stage of infection. Induction of autophagy enhances IBDV replication, whereas inhibition of autophagy impairs viral replication. We also demonstrated that IBDV infection induced autophagosome–lysosome fusion, but without active degradation of their contents. Moreover, inhibition of fusion or of lysosomal hydrolysis activity significantly reduced viral replication, indicating that virions utilised the low pH environment of acidic organelles to facilitate viral maturation. Using immuno-transmission electron microscopy (TEM), we observed that a large number of intact IBDV virions were arranged in a lattice surrounded by p62 proteins, some of which laid between virions. Additionally, many virions were encapsulated within the vesicular membranes with an obvious release stage observed by TEM. The autophagic endosomal pathway facilitates low pH-mediated maturation of viral proteins and membrane-mediated release of progeny virions.IMPORTANCE IBDV is the most extensively studied virus in terms of molecular characteristics and pathogenesis; however, mechanisms underlying the IBDV life cycle require further exploration. The present study demonstrated that autophagy enhances viral replication at the late stage of infection, and the autophagy pathway facilitates IBDV replication complex function and virus assembly, which is critical to completion of the virus life cycle. Moreover, the virus hijacks the autophagic vacuoles to mature in an acidic environment and release progeny virions in a membrane-mediated cell-to-cell manner. This autophagic endosomal pathway is proposed as a new mechanism that facilitates IBDV maturation, release, and re-internalisation. This study presents a concordance in exit strategies among some RNA and DNA viruses, which exploit autophagy pathway for their release from cells.

Volpato G, Dioli M, Di Nardo A (2017)

Piebald Camels

Pastoralism 7 (1), 3

Abstract

Animal breeds are the diverse outcome of the thousands-year-long process of livestock domestication. Many of these breeds are piebald, resulting from the artificial selection by pastoralists of animals bearing a genetic condition known as leucism, and selected for their productive, behavioural, or aesthetical traits. Piebald dromedary camels have not been studied or discussed before, and their same existence is often overlooked. Based on fieldwork in Western Sahara, direct observations across Northern and East Africa and the Middle East, and a literature review, we address the morphological and behavioural traits, geographical distribution, taxonomy, and material and cultural importance of piebald (painted) camels. They are a hundreds-year-old camel breed used for caravans, as mounts, and for aesthetical and cultural reasons across Sudan, Niger, Mali, Mauritania, Western Sahara, and Morocco. While they are increasingly bred out of a pastoral context for tourism and entertainment in the Canary Islands, mainland Europe, and the USA, in part of their original African range, piebald camels are under threat due to wars, droughts, and demise of pastoral livelihoods. More research is needed about these ‘beautiful and dignified’ animals.

Volpato G, Di Nardo A (2017)

The role of Nucularia perrinii Batt. (Chenopodiaceae) in the camel-based Sahrawi social-ecological system

Journal of Ethnobiology and Ethnomedicine 13 (1), 12

Abstract

BACKGROUND: Pastoral social-ecological systems (SESs) are adaptive and complex systems rooted in the extensive exploitation of forage plants for livestock-based livelihoods and culture. There are species and relations that are foundational to the existence of these SESs. Nucularia perrinii Batt. (Chenopodiaceae) is an endemic halophyte plant of central and western Sahara seldom cited in the scientific literature. The objective of this study was to investigate the role of this plant in the SES of the Sahrawi camel nomads of Western Sahara. METHODS: The data analyzed were collected in the Sahrawi refugee camps of Algeria and in Western Sahara between 2006 and 2010. Fieldwork included semi-structured (n = 38) and retrospective (n = 12) interviews with Sahrawi refugees, nomads, and camel owners about N. perrinii and associated topics (e.g. distribution, importance for camels, camel diseases, associated grazing practices, other forage plants, etc.). RESULTS: Askaf, as the Sahrawi call the plant, is crucial to camels' survival, providing salts and water even during dry spells. It holds a pivotal role in the Sahrawi culture, defining the geographical boundaries of the Sahrawi SES and relating the grazing territory with the taste it gives to camel milk, which support the inclusion of askaf as a main element of Sahrawi cultural identity. CONCLUSIONS: We argue that N. perrinii ties the ecology of the western Sahara desert with camel husbandry and associated livelihoods, and further with the culture and worldview of the Sahrawi nomads. We stress the keystone role that some forage plants may have in extensive pastoral SESs worldwide.

Topliff C L, Alkheraif A A, Kuszynski C A, Davis W C, Steffen D J, Schmitz J A, Eskridge K M, Charleston B, Henningson J N, Kelling C L (2017)

Experimental acute infection of alpacas with bovine viral diarrhea virus 1 subgenotype b alters peripheral blood and GALT leukocyte subsets

Journal of Veterinary Diagnostic Investigation 29 (2), 186-192

Abstract

Bovine viral diarrhea virus (BVDV) is a pathogen in cattle and alpacas ( Vicugna pacos), causing acute and persistent BVDV infections. We characterized the effect of acute BVDV infection on the immune system of alpacas by determining lymphocyte subpopulations in peripheral blood and gut-associated lymphoid tissues (GALT) as well as serum interferon levels. Alpacas were experimentally infected with BVDV-1b (strain CO-06). Peripheral blood leukocytes were isolated at 0, 3, 6, and 9 d postinfection (dpi), and leukocytes of GALT at 9 dpi, and evaluated using flow cytometry. Serum interferon levels were determined daily. Flow cytometric analyses of peripheral blood leukocytes showed a significant decrease in CD4+, CD8+, and alphabeta T-lymphocytes at 3 dpi. CD8+ lymphocytes were significantly increased, and activated lymphocytes were significantly decreased in the C3-stomach region in BVDV-infected alpacas. Serum interferon concentrations significantly increased in BVDV-infected alpacas at 3-6 dpi, peaking at 3 dpi. Our study confirms that BVDV can be a primary acute pathogen in alpacas and that it induces an interferon response and alters leukocyte subset populations. The changes in the proportion of T-lymphocytes during the early stages of BVDV infection may result in transient immunosuppression that may contribute to secondary bacterial and viral infections, similar to cattle.

Taylor G (2017)

Animal models of respiratory syncytial virus infection

Vaccine 35 (3), 469-480

Abstract

Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host. Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore, interpretation of findings from many rodent and NHP models of vaccine-enhanced hRSV disease has been confounded by sensitisation to non-viral antigens present in the vaccine and challenge virus. Studies of non-human pneumoviruses in their native hosts are more likely to reflect the pathogenesis of natural hRSV infection, and experimental infection of calves with bRSV and of mice with PVM result in clinical disease and extensive pulmonary pathology. These animal models have not only been of value in studies on mechanisms of immunity to and the pathogenesis of pneumovirus infections but have also been used to evaluate hRSV vaccine concepts. Furthermore, the similarities between the epidemiology of bRSV in calves and hRSV in infants and the high level of genetic and antigenic similarity between bRSV and hRSV, make the calf model of bRSV infection a relevant model for preclinical evaluation of hRSV vaccine candidates which contain proteins that are conserved between hRSV and bRSV.

Silaghi C, Santos A S, Gomes J, Christova I, Matei I A, Walder G, Domingos A, Bell-Sakyi L, Sprong H, von Loewenich F D, Oteo J A, de la Fuente J, Dumler J S (2017)

Guidelines for the direct detection of Anaplasma spp. in diagnosis and epidemiological studies

Vector-Borne and Zoonotic Diseases 17 (1), Dec-22

Abstract

The genus Anaplasma (Rickettsiales: Anaplasmataceae) comprises obligate intracellular Gram-negative bacteria that are mainly transmitted by ticks, and currently includes six species: Anaplasma bovis, Anaplasma centrale, Anaplasma marginale, Anaplasma phagocytophilum, Anaplasma platys, and Anaplasma ovis. These have long been known as etiological agents of veterinary diseases that affect domestic and wild animals worldwide. A zoonotic role has been recognized for A. phagocytophilum, but other species can also be pathogenic for humans. Anaplasma infections are usually challenging to diagnose, clinically presenting with nonspecific symptoms that vary greatly depending on the agent involved, the affected host, and other factors such as immune status and coinfections. The substantial economic impact associated with livestock infection and the growing number of human cases along with the risk of transfusion-transmitted infections, determines the need for accurate laboratory tests. Because hosts are usually seronegative in the initial phase of infection and serological cross-reactions with several Anaplasma species are observed after seroconversion, direct tests are the best approach for both case definition and epidemiological studies. Blood samples are routinely used for Anaplasma spp. screening, but in persistently infected animals with intermittent or low-level bacteremia, other tissues might be useful. These guidelines have been developed as a direct outcome of the COST action TD1303 EURNEGVEC (“European Network of Neglected Vectors and Vector-Borne Diseases”). They review the direct laboratory tests (microscopy, nucleic acid-based detection and in vitro isolation) currently used for Anaplasma detection in ticks and vertebrates and their application.

Schwartz J C, Gibson M S, Heimeier D, Koren S, Phillippy A M, Bickhart D M, Smith T P L, Medrano J F, Hammond J A (2017)

The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation

Immunogenetics 69 (4), 255-269

Abstract

Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ, and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination.

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