Publications

Publications

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

There were a total of 1528 results for your search.
Sanz Bernardo B, Goodbourn S, Baron M D (2017)

Control of the induction of type I interferon by peste des petits ruminants virus

PLOS ONE 12 (5), e0177300

Abstract

Peste des petits ruminants virus (PPRV) is a morbillivirus that produces clinical disease in goats and sheep. We have studied the induction of interferon-? (IFN-?) following infection of cultured cells with wild-type and vaccine strains of PPRV, and the effects of such infection with PPRV on the induction of IFN-? through both MDA-5 and RIG-I mediated pathways. Using both reporter assays and direct measurement of IFN-? mRNA, we have found that PPRV infection induces IFN-? only weakly and transiently, and the virus can actively block the induction of IFN-?. We have also generated mutant PPRV that lack expression of either of the viral accessory proteins (V&C) to characterize the role of these proteins in IFN-? induction during virus infection. Both PPRV_?V and PPRV_?C were defective in growth in cell culture, although in different ways. While the PPRV V protein bound to MDA-5 and, to a lesser extent, RIG-I, and over-expression of the V protein inhibited both IFN-? induction pathways, PPRV lacking V protein expression can still block IFN-? induction. In contrast, PPRV C bound to neither MDA-5 nor RIG-I, but PPRV lacking C protein expression lost the ability to block both MDA-5 and RIG-I mediated activation of IFN-?. These results shed new light on the inhibition of the induction of IFN-? by PPRV.

Peacock T P, Benton D J, James J, Sadeyen J-R, Chang P, Sealy J E, Bryant J E, Martin S R, Shelton H, Barclay W S, Iqbal M (2017)

Immune escape variants of H9N2 influenza viruses containing deletions at the haemagglutinin receptor binding site retain fitness in vivo and display enhanced zoonotic characteristics

Journal of Virology ,

Abstract

H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa where they pose a threat to human health, both as zoonotic agents and as potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions, however vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza antigen, haemagglutinin (HA). Using selection with HA specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBS). Here, we analysed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that the mutant viruses with RBS deletions are able to escape polyclonal antisera binding and are able to infect and transmit between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells, however the mutant HAs also displayed a reduced pH and thermal stability. In summary we infer that variant influenza viruses with deletions in 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude these viruses would be unlikely to transmit human-to-human by an airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses, as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence.IMPORTANCE Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden, however, influenza viruses are able to rapidly evolve to escape immune pressure in a process known as ‘antigenic drift’. Previously we experimentally generated antigenic drift variants in the laboratory, and here we test our ‘drifted’ viruses to assess their zoonotic infection characteristics and transmissibility in chickens. We found that the ‘drifted’ viruses were able to infect and transmit between chickens and showed increased binding to human-like receptors. However the ‘drift’ mutant viruses displayed reduced stability and, we predict, would be unlikely to be able to transmit human-to-human and cause an influenza pandemic. These results demonstrate the complex relationship between antigenic drift and potential of avian influenza viruses to infect humans.

Chakraborty P, Vervelde L, Dalziel R G, Wasson P S, Nair V, Dutia B M, Kaiser P (2017)

Marek's disease virus infection of phagocytes: a de novo in vitro infection model

Journal of General Virology 98 (5), 1080-1088

Abstract

Marek's disease virus (MDV) is an alphaherpesvirus that induces T-cell lymphomas in chickens. Natural infections in vivo are caused by the inhalation of infected poultry house dust and it is presumed that MDV infection is initiated in the macrophages from where the infection is passed to B cells and activated T cells. Virus can be detected in B and T cells and macrophages in vivo, and both B and T cells can be infected in vitro. However, attempts to infect macrophages in vitro have not been successful. The aim of this study was to develop a model for infecting phagocytes [macrophages and dendritic cells (DCs)] with MDV in vitro and to characterize the infected cells. Chicken bone marrow cells were cultured with chicken CSF-1 or chicken IL-4 and chicken CSF-2 for 4 days to produce macrophages and DCs, respectively, and then co-cultured with FACS-sorted chicken embryo fibroblasts (CEFs) infected with recombinant MDV expressing EGFP. Infected phagocytes were identified and sorted by FACS using EGFP expression and phagocyte-specific mAbs. Detection of MDV-specific transcripts of ICP4 (immediate early), pp38 (early), gB (late) and Meq by RT-PCR provided evidence for MDV replication in the infected phagocytes. Time-lapse confocal microscopy was also used to demonstrate MDV spread in these cells. Subsequent co-culture of infected macrophages with CEFs suggests that productive virus infection may occur in these cell types. This is the first report of in vitro infection of phagocytic cells by MDV.

Zhang F, Perez-Martin E, Juleff N, Charleston B, Seago J (2017)

A replication-competent foot-and-mouth disease virus expressing a luciferase reporter

Journal of Virological Methods 247, 38-44

Abstract

Bioluminescence is a powerful tool in the study of viral infection both in vivo and in vitro. Foot-and-mouth disease virus (FMDV) has a small RNA genome with a limited tolerance to foreign RNA entities. There has been no success in making a reporter FMDV expressing a luciferase in infected cell culture supernatants. We report here for the first time a replication-competent FMDV encoding Nanoluciferase, named as Nano-FMDV. Nano-FMDV is genetically stable during serial passages in cells and exhibits growth kinetics and plaque morphology similar to its parental virus. There are applications for the use of Nano-FMDV such as real-time monitoring of FMDV replication in vitro and in vivo.

Tchilian E, Holzer B (2017)

Harnessing local immunity for an effective universal swine influenza vaccine

Viruses 9 (5),
Publisher’s version: http://dx.doi.org/10.3390/v9050098

Abstract

Influenza A virus infections are a global health threat to humans and are endemic in pigs, contributing to decreased weight gain and suboptimal reproductive performance. Pigs are also a source of new viruses of mixed swine, avian, and human origin, potentially capable of initiating human pandemics. Current inactivated vaccines induce neutralising antibody against the immunising strain but rapid escape occurs through antigenic drift of the surface glycoproteins. However, it is known that prior infection provides a degree of cross-protective immunity mediated by cellular immune mechanisms directed at the more conserved internal viral proteins. Here we review new data that emphasises the importance of local immunity in cross-protection and the role of the recently defined tissue-resident memory T cells, as well as locally-produced, and sometimes cross-reactive, antibody. Optimal induction of local immunity may require aerosol delivery of live vaccines, but it remains unclear how long protective local immunity persists. Nevertheless, a universal vaccine might be extremely useful for disease prevention in the face of a pandemic. As a natural host for influenza A viruses, pigs are both a target for a universal vaccine and an excellent model for developing human influenza vaccines.

Simmonds P, Adams M J, Benko M, Breitbart M, Brister J R, Carstens E B, Davison A J, Delwart E, Gorbalenya A E, Harrach B, Hull R, King A M Q, Koonin E V, Krupovic M, Kuhn J H, Lefkowitz E J, Nibert M L, Orton R, Roossinck M J, Sabanadzovic S, Sullivan M B, Suttle C A, Tesh R B, van der Vlugt R A, Varsani A, Zerbini F M (2017)

Consensus statement: virus taxonomy in the age of metagenomics

Nature Reviews Microbiology 15 (3), 161-168

Abstract

The number and diversity of viral sequences that are identified in metagenomic data far exceeds that of experimentally characterized virus isolates. In a recent workshop, a panel of experts discussed the proposal that, with appropriate quality control, viruses that are known only from metagenomic data can, and should be, incorporated into the official classification scheme of the International Committee on Taxonomy of Viruses (ICTV). Although a taxonomy that is based on metagenomic sequence data alone represents a substantial departure from the traditional reliance on phenotypic properties, the development of a robust framework for sequence-based virus taxonomy is indispensable for the comprehensive characterization of the global virome. In this Consensus Statement article, we consider the rationale for why metagenomic sequence data should, and how it can, be incorporated into the ICTV taxonomy, and present proposals that have been endorsed by the Executive Committee of the ICTV.

Sadigh Y, Nair V (2017)

A review on PML nuclear bodies and their interaction with herpesviruses

Annals of Virology and Research 3 (1), 1027

Abstract

PML nuclear bodies (PNBs) are proteinaceous structures which predominantly reside inside the nuclei of mammalian cells. Their antiviral effects on a wide range of DNA and RNA viruses are shown. Viruses have evolved a diverse range of mechanisms to overcome the antiviral effect of PNBs. In particular, herpesviruses enter into an association with PNBs to control such antiviral effects. An outcome of this association is switching between the two life cycles of the virus. In this manuscript, we have reviewed our current knowledge on the biology of PNBs and the interplay between them and herpesviruses with an emphasis on the factors that affect the life cycle of the virus.

Rohaim M A, El Naggar R F, Helal A M, Hussein H A, Munir M (2017)

Reverse spillover of avian viral vaccine strains from domesticated poultry to wild birds

Vaccine 35 (28), 3523-3527

Abstract

Transmission of viruses from the commercial poultry to wild birds is an emerging paradigm of livestock–wildlife interface. Here, we report the identification and isolation of vaccine strains of avian paramyxovirus serotype 1 (APMV1) and avian coronaviruses (ACoV) from different wild bird species across eight Egyptian governorates between January 2014 and December 2015. Surveillance of avian respiratory viruses in free-ranging wild birds (n = 297) identified three species that harboured or excreted APMV1 and ACoVs. Genetic characterization and phylogenetic analysis of recovered viruses revealed a close association with the most widely utilized vaccine strains in the country. These results highlight the potential spillover of vaccine-viruses probably due to extensive use of live-attenuated vaccines in the commercial poultry, and close interaction between domesticated and wild bird populations. Further exploring the full spectrum of vaccine-derived viral vaccine strains in wild birds might help to assess the emergence of future wild-birds origin viruses.

Mwangi W N, Vasoya D, Kgosana L B, Watson M, Nair V (2017)

Differentially expressed genes during spontaneous lytic switch of Marek's disease virus in lymphoblastoid cell lines determined by global gene expression profiling

Journal of General Virology 98 (4), 779-790

Abstract

Marek’s disease virus (MDV), an alphaherpesvirus of poultry, causes Marek’s disease and is characterized by visceral CD4+TCR??+ T-cell lymphomas in susceptible hosts. Immortal cell lines harbouring the viral genome have been generated from ex vivo cultures of MD tumours. As readily available sources of large numbers of cells, MDV-transformed lymphoblastoid cell lines (LCLs) are extremely valuable for studies of virus–host interaction. While the viral genome in most cells is held in a latent state, minor populations of cells display spontaneous reactivation identifiable by the expression of lytic viral genes. Spontaneous reactivation in these cells presents an opportunity to investigate the biological processes involved in the virus reactivation. For detailed characterization of the molecular events associated with reactivation, we used two lymphoblastoid cell lines derived from lymphomas induced by pRB1B-UL47eGFP, a recombinant MDV engineered to express enhanced green fluorescent protein (EGFP) fused with the UL47. We used fluorescence-activated cell sorting to purify the low-frequency EGFP-positive cells with a spontaneously activating viral genome from the majority EGFP-negative cells and analysed their gene expression profiles by RNA-seq using Illumina HiSeq2500. Ingenuity pathway analysis on more than 2000 differentially expressed genes between the lytically infected (EGFP-positive) and latently infected (EGFP-negative) cell populations identified the biological pathways involved in the reactivation. Virus-reactivating cells exhibited differential expression of a significant number of viral genes, with hierarchical differences in expression levels. Downregulation of a number of host genes including those directly involved in T-cell activation, such as CD3, CD28, ICOS and phospholipase C, was also noticed in the LCL undergoing lytic switch.

Mills M K, Michel K, Pfannenstiel R S, Ruder M G, Veronesi E, Nayduch D (2017)

Culicoides-virus interactions: infection barriers and possible factors underlying vector competence

Current Opinion in Insect Science 22, 7-15

Abstract

In the United States, Culicoides midges vector arboviruses of economic importance such as bluetongue virus and epizootic hemorrhagic disease virus. A limited number of studies have demonstrated the complexities of midge–virus interactions, including dynamic changes in virus titer and prevalence over the infection time course. These dynamics are, in part, dictated by mesenteron infection and escape barriers. This review summarizes the overarching trends in viral titer and prevalence throughout the course of infection. Essential barriers to infection and dissemination in the midge are highlighted, along with heritable and extrinsic factors that likely contribute to these barriers. Next generation molecular tools and techniques, now available for Culicoides midges, give researchers the opportunity to test how these factors contribute to vector competence.

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