Publications

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

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Banyard A C, Wang Z, Parida S (2014)

Peste des petits ruminants virus, Eastern Asia (letter).

Emerging Infectious Diseases 20 (12), 2176-2178

Abstract

Peste des petits ruminants virus (PPRV) is reported globally with increasing frequency. Recently, PPRV has been detected in areas where it is considered endemic and in neighboring areas where it previously has not been reported. The reporting of “first cases” in regions where PPRV has been considered endemic is of little surprise and perhaps represents increased interest both in agricultural practices and diagnostic capacity (1–3). Increased development of the small ruminant health sector, expanding small ruminant populations, increased trade movement, and rinderpest eradication might all have affected PPRV detection (4). The latter theory is of great interest because rinderpest eradication may have affected the epidemiology of PPRV through complete removal cross-protective rinderpest infection of small ruminants and cessation of small ruminant vaccination with the rinderpest vaccine to prevent PPRV infection. Indeed, the potential effect of rinderpest eradication on PPRV epidemiology should not be understated because it might have profoundly affected PPRV emergence by enabling free transmission and spread of the virus, perhaps overcoming the genetic and geographic bottlenecks created by rinderpest circulation and/or the use of rinderpest vaccines. In addition, rinderpest eradication has highlighted the possibility that PPRV could be eradicated by using comparable systems and tools. Once the current situation has been resolved, full genetic analysis of the viruses causing the outbreaks should be conducted because it might indicate the direction of spread. A further area of interest is the application and choice of control measures. Although predicting the spread of a viral pathogen is impossible, especially across the vast distances involved in the current reports, the experiences in China might influence future responses to incursions of PPRV into areas where PPRV previously has not been documented. The current lack of disease in areas where vaccination was reported in 2010 could explain the continued absence of disease from such areas while other regions are significantly affected (10). Effective vaccines against PPRV have been available for decades and will now, as both reactive and preventive tools, aid in controlling and preventing onward transmission of this viral pathogen. Once the situation in China is under control, where this emerging infection of small ruminants will appear next remains to be seen.

Abstract

Swine influenza virus is one of the most important pathogens involved in the swine respiratory disease complex. Recent serological surveys showed a high prevalence of swine influenza strains belonging to the H1N1, H1N2 and H3N2 subtypes circulating in pigs in Spain. However, little is known about their genome sequence. Five swine influenza strains were isolated from some unrelated outbreaks occurred during 2006-2007, and their complete genome sequences were determined. Phylogenetic analysis revealed that they belonged to the lineages "Avian-Like" H1N1, "Human-Like" H3N2, and "Human-Like" H1N2, showing tight relationships with early or contemporary strains described in Europe. Notably, one virus of the H1N2 subtype showed genetic and antigenic divergence with the European contemporary strains or vaccinal strains of the same subtype, suggesting that some local and divergent clusters of the virus may pass unnoticed in routinary subtyping. Finally, analysis on the entire pattern of genome segments suggested that a second reassortment event could have influenced the evolution of that divergent H1N2 strain.

Abstract

Cytoplasmic incompatibility (CI) induced by the endosymbiont Wolbachia pipientis causes complex patterns of crossing sterility between populations of the Culex pipiens group of mosquitoes. The molecular basis of the phenotype is yet to be defined. In order to investigate what host changes may underlie CI at the molecular level, we examined the transcription of a homolog of the Drosophila melanogaster gene grauzone that encodes a zinc finger protein and acts as a regulator of female meiosis, in which mutations can cause sterility. Upregulation was observed in Wolbachia-infected C. pipiens group individuals relative to Wolbachia-cured lines and the level of upregulation differed between lines that were reproductively incompatible. Knockdown analysis of this gene using RNAi showed an effect on hatch rates in a Wolbachia infected Culex molestus line. Furthermore, in later stages of development an effect on developmental progression in CI embryos occurs in bidirectionally incompatible crosses. The genome of a wPip Wolbachia strain variant from Culex molestus was sequenced and compared with the genome of a wPip variant with which it was incompatible. Three genes in inserted or deleted regions were newly identified in the C. molestus wPip genome, one of which is a transcriptional regulator labelled wtrM. When this gene was transfected into adult Culex mosquitoes, upregulation of the grauzone homolog was observed. These data suggest that Wolbachia-mediated regulation of host gene expression is a component of the mechanism of cytoplasmic incompatibility.

Abstract

Almost 30 years after its initial discovery, infection with the human immunodeficiency virus-1 (HIV-1) remains incurable and the virus persists due to reservoirs of latently infected CD4(+) memory T-cells and sanctuary sites within the infected individual where drug penetration is poor. Reactivating latent viruses has been a key strategy to completely eliminate the virus from the host, but many difficulties and unanswered questions remain. In this review, the latest developments in HIV-persistence and latency research are presented.

Abstract

Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA viruses. The family includes several emerging and re-emerging viruses of humans, animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus. Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and the different structural proteins, one or several non-structural proteins. These non-structural proteins are not always essential for virus growth and replication but can play an important role in viral pathogenesis through their interaction with the host innate immune system. In this review, we will summarize current knowledge and understanding of insect-borne bunyavirus non-structural protein function(s) in vertebrate, plant and arthropod.

Varela M, Schnettler E, Caporale M, Murgia C, Barry G, McFarlane M, McGregor E, Piras I M, Shaw A, Lamm C, Janowicz A, Beer M, Glass M, Herder V, Hahn K, Baumgärtner W, Kohl A, Palmarini M (2013)

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

PLOS Pathogens 9 (1), e1003133

Abstract

Schmallenberg virus (SBV) was discovered in Germany (near the town of Schmallenberg) in November 2011 and since then has been found to be the cause of malformations and stillbirths in ruminants. SBV has spread very rapidly to many European countries including the Netherlands, Belgium, France and the United Kingdom. Very little is known about the biological properties of this virus and there is no vaccine available. In this study (i) we developed an approach (called reverse genetics) that allows the recovery of "synthetic" SBV under laboratory conditions; (ii) we developed a mouse model of infection for SBV; (iii) we showed that SBV replicates in neurons of experimentally infected mice similar to naturally infected lambs and calves; (iv) we developed viral mutants that are not as pathogenic as the original virus due to the inability to counteract the host cell defenses; and v) we identified mutations that are associated with increased virulence. This work provides the experimental tools to understand how this newly emerged virus causes disease in ruminants. In addition, it will now be possible to manipulate the SBV genome in order to develop highly effective vaccines.

Shaw A E, Mellor D J, Purse B V, Shaw P E, McCorkell B F, Palmarini M (2013)

Transmission of Schmallenberg virus in a housed dairy herd in the UK

Veterinary Record 173 (24), 609-609

Abstract

Johne's disease (JD) is an infectious, progressive, gastrointestinal disease affecting ruminants. Calves are mostly infected in their first six months of life, or in utero. We investigated the impact of specific periparturient management practices on within-herd JD prevalence and economic losses foregone in UK dairy herds by means of data synthesis (systematic appraisal of published evidence and expert elicitation) and use of a pre-existing simulation model. Our results show the scarcity of accurate estimates of the impact of specific periparturient management practices on within-herd JD prevalence, which could, in part, be explained by challenges associated with the chronic nature of JD. Management practices aiming to limit the faecal-oral transmission route of Mycobacterium avium subspecies paratuberculosis (MAP) were found to be most effective at reducing within-herd prevalence of JD. Practices aiming to limit MAP transmission via colostrum and milk were found to be less effective. Losses foregone for a hypothetical herd of 200 milking cows were considerable; based on the assumptions, it is reasonable to expect between £7000 and £11,000 of losses foregone when management practices are implemented as a package of measures. The findings of this study are envisaged to enable farmers and veterinarians to make more informed decisions on changes to periparturient management to control JD.

Abstract

Mechanisms by which certain RNA viruses, such as hepatitis C virus, establish persistent infections and cause chronic disease are of fundamental importance in viral pathogenesis. Mammalian positive-stranded RNA viruses establishing persistence typically possess genome-scale ordered RNA secondary structure (GORS) in their genomes. Murine norovirus (MNV) persists in immunocompetent mice and provides an experimental model to functionally characterize GORS. Substitution mutants were constructed with coding sequences in NS3/4- and NS6/7-coding regions replaced with sequences with identical coding and (di-)nucleotide composition but disrupted RNA secondary structure (F1, F2, F1/F2 mutants). Mutants replicated with similar kinetics to wild-type (WT) MNV3 in RAW264.7 cells and primary macrophages, exhibited similar (highly restricted) induction and susceptibility to interferon-coupled cellular responses and equal replication fitness by serial passaging of co-cultures. In vivo, both WT and F1/F2 mutant viruses persistently infected mice, although F1, F2 and F1/F2 mutant viruses were rapidly eliminated 1-7 days post-inoculation in competition experiments with WT. F1/F2 mutants recovered from tissues at 9 months showed higher synonymous substitution rates than WT and nucleotide substitutions that potentially restored of RNA secondary structure. GORS plays no role in basic replication of MNV but potentially contributes to viral fitness and persistence in vivo.

Abstract

Background: The bacterial surface protein internalin (InlA) is a major virulence factor of the food-born pathogen Listeria monocytogenes. It plays a critical role in the bacteria crossing the host intestinal barrier by a species-specific interaction with the cell adhesion molecule E-cadherin. In mice, the interaction of InlA with murine E-cadherin is impaired due to sequence-specific binding incompatibilities. We have previously used the approach of 'murinisation' to establish an oral listeriosis infection model in mice by exchanging two amino acid residues in InlA. This dramatically increases binding to mouse E-cadherin. In the present study, we have used bioluminescent murinised and non-murinised Listeria strains to examine the spatiotemporal dissemination of Listeria in four diverse mouse genetic backgrounds after oral inoculation. Results: The murinised Listeria monocytogenes strain showed enhanced invasiveness and induced more severe infections in all four investigated mouse inbred strains compared to the non-murinised Listeria strain. We identified C57BL/6J mice as being most resistant to orally acquired listeriosis whereas C3HeB/FeJ, A/J and BALB/cJ mice were found to be most susceptible to infection. This was reflected in faster kinetics of Listeria dissemination, higher bacterial loads in internal organs, and elevated serum levels of IL-6, IFN-gamma, TNF-alpha and CCL2 in the susceptible strains as compared to the resistant C57BL/6J strain. Importantly, murinisation of InlA did not cause enhanced invasion of Listeria monocytogenes into the brain. Conclusion: Murinised Listeria are able to efficiently cross the intestinal barrier in mice from diverse genetic backgrounds. However, expression of murinized InlA does not enhance listerial brain invasion suggesting that crossing of the blood brain barrier and crossing of the intestinal epithelium are achieved by Listeria monocytogenes through different molecular mechanisms.

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