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Ian M. Jones
University of Reading, Reading, United Kingdom

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Journal article
Published: 28 July 2021 in Blood
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A subset of patients with COVID-19 become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill COVID-19 patients are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesised that platelets might be susceptible to activation by anti-SARS-CoV-2 antibodies and contribute to thrombosis. We found that immune complexes containing recombinant SARS-CoV-2 spike protein and anti-spike IgG enhanced platelet-mediated thrombosis on von Willebrand Factor in vitro, but only when the glycosylation state of the Fc domain was modified to correspond with the aberrant glycosylation previously identified in patients with severe COVID-19. Furthermore, we found that activation was dependent on FcγRIIA and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by therapeutic small molecules R406 (fostamatinib) and ibrutinib that inhibit tyrosine kinases Syk and Btk respectively or by the P2Y12 antagonist cangrelor.

ACS Style

Alexander P Bye; Willianne Hoepel; Joanne L Mitchell; Sophie Mélanie Jégouic; Silvia Loureiro; Tanya Sage; Gestur Vidarsson; Jan Nouta; Manfred Wuhrer; Steven W. de Taeye; Marit van Gils; Neline Kriek; Nichola Cooper; Ian Jones; Jeroen Den Dunnen; Jonathan M Gibbins. Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets. Blood 2021, 1 .

AMA Style

Alexander P Bye, Willianne Hoepel, Joanne L Mitchell, Sophie Mélanie Jégouic, Silvia Loureiro, Tanya Sage, Gestur Vidarsson, Jan Nouta, Manfred Wuhrer, Steven W. de Taeye, Marit van Gils, Neline Kriek, Nichola Cooper, Ian Jones, Jeroen Den Dunnen, Jonathan M Gibbins. Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets. Blood. 2021; ():1.

Chicago/Turabian Style

Alexander P Bye; Willianne Hoepel; Joanne L Mitchell; Sophie Mélanie Jégouic; Silvia Loureiro; Tanya Sage; Gestur Vidarsson; Jan Nouta; Manfred Wuhrer; Steven W. de Taeye; Marit van Gils; Neline Kriek; Nichola Cooper; Ian Jones; Jeroen Den Dunnen; Jonathan M Gibbins. 2021. "Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets." Blood , no. : 1.

Feature
Published: 27 July 2021 in The Biochemist
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Virus-like particles (VLPs) are nanoscale structures that are mimics of virus particles themselves. They are stripped of any infection risk but can perform like viruses in some tasks although they are unable to spread. They are inherently safe and may offer additional advantages when compared to the viruses from which they derive. If they are produced by a recombinant route, as is very common, they can be modified by alteration of the sequences used to add functionality their parental versions did not possess, such as staying in a particular conformation, carrying different cargoes or targeting specific cells. It is probably true that VLPs are ascribed more promise than may ever be realized but their positive attributes are very real, they have already appeared as successful products and their potential is certainly far from exhausted.

ACS Style

Ian Jones; Polly Roy. Small is beautiful: virus-like particles as vaccines. The Biochemist 2021, 43, 18 -21.

AMA Style

Ian Jones, Polly Roy. Small is beautiful: virus-like particles as vaccines. The Biochemist. 2021; 43 (4):18-21.

Chicago/Turabian Style

Ian Jones; Polly Roy. 2021. "Small is beautiful: virus-like particles as vaccines." The Biochemist 43, no. 4: 18-21.

Journal article
Published: 11 March 2021 in Wellcome Open Research
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Background: Miniaturised bioassays permit diagnostic testing near the patient, and the results can be recorded digitally using inexpensive cameras including smartphone and mobile phone cameras. Although digital cameras are now inexpensive and portable, the minimum performance required for microfluidic diagnostic bioassays has not been defined. We present a systematic comparison of a wide range of different digital cameras for capturing and measuring results of microfluidic bioassays and describe a framework to specify performance requirements to quantify immunoassays. Methods: A set of 200 µm diameter microchannels was filled with a range of concentrations of dyes used in colorimetric and fluorometric enzyme immunoassays. These were imaged in parallel using cameras of varying cost and performance ranging from <£30 to >£500. Results: Higher resolution imaging allowed larger numbers of microdevices to be resolved and analysed in a single image. In contrast, low quality cameras were still able to quantify results but for fewer samples. In some cases, an additional macro lens was added to focus closely. If image resolution was sufficient to identify individual microfluidic channels as separate lines, all cameras were able to quantify a similar range of concentrations of both colorimetric and fluorometric dyes. However, the mid-range cameras performed better, with the lowest cost cameras only allowing one or two samples to be quantified per image. Consistent with these findings, we demonstrate that quantitation (to determine endpoint titre) of antibodies against dengue and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses is possible using a wide range of digital imaging devices including the mid-range smartphone iPhone 6S and a budget Android smartphone costing <£50. Conclusions: In conclusion, while more expensive and higher quality cameras allow larger numbers of devices to be simultaneously imaged, even the lowest resolution and cheapest cameras were sufficient to record and quantify immunoassay results.

ACS Style

Sophie M. Jégouic; Ian M. Jones; Alexander D. Edwards. Affordable mobile microfluidic diagnostics: minimum requirements for smartphones and digital imaging for colorimetric and fluorometric anti-dengue and anti-SARS-CoV-2 antibody detection. Wellcome Open Research 2021, 6, 57 .

AMA Style

Sophie M. Jégouic, Ian M. Jones, Alexander D. Edwards. Affordable mobile microfluidic diagnostics: minimum requirements for smartphones and digital imaging for colorimetric and fluorometric anti-dengue and anti-SARS-CoV-2 antibody detection. Wellcome Open Research. 2021; 6 ():57.

Chicago/Turabian Style

Sophie M. Jégouic; Ian M. Jones; Alexander D. Edwards. 2021. "Affordable mobile microfluidic diagnostics: minimum requirements for smartphones and digital imaging for colorimetric and fluorometric anti-dengue and anti-SARS-CoV-2 antibody detection." Wellcome Open Research 6, no. : 57.

Preprint content
Published: 24 February 2021
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Tick Borne Encephalitis Virus (TBEV) is an important human arthropod-borne virus, which causes tick-borne encephalitis (TBE), an acute viral infection of the central nervous system (CNS) that causes neurological symptoms of varying severity. TBEV is prevalent in large parts of central- and northern-Europe as well as Northern Asia, and strains of varying pathogenicity have been described. Both host and viral specific characteristics have been postulated to determine the outcome of TBEV infection, but the exact basis of their clinical variability remains undefined. Here, we report the generation of Spinach RNA aptamer labelled TBEV replicons of high (Hypr) and low (Vs) pathogenicity isolates and perform the first direct comparison of both strains in cell culture. We show that pathogenic Hypr replicates to higher levels than Vs in mammalian cells, but not in arthropod cells, and that the basis of this difference maps to the NS5 region, encoding the methyltransferase and RNA polymerase. For both Hypr and Vs strains, NS5 and the viral genome localized to defined intracellular structures typical of positive strand RNA viruses, but Hypr was associated with significant activation of IRF-3, caspase-3 and caspase-8, whilst Vs activated Akt, affording protection against caspase-mediated apoptosis. Activation of TIAR and the formation of cytoplasmic stress granules were an additional early feature of Vs but not Hypr replication. Taken together, these findings highlight NS5 and novel host cell responses as key underling factors for the differential clinical characteristics of TBEV strains. Importance Tick-borne encephalitis virus (TBEV) is an emerging virus of the flavivirus family spread by ticks. Tick bite can transfer the virus and lead to a febrile infection, Tick-borne encephalitis, of varying severity. There is no specific therapeutic treatment and control in endemic areas is by vaccination. The basis of the different pathologies shown following TBEV infection, from mild to fatal, is not clear although the virus genotype clearly has a role. Mapping the basis of their differential effects would allow focus on the stages of the replication cycle responsible, which might guide the development of therapeutic interventions or the creation of purposefully attenuated strains as candidate vaccines.

ACS Style

Niluka Goonawardane; Laura Upstone; Mark Harris; Ian M Jones. Identification of host antiviral genes differentially induced by clinically diverse strains of Tick-Borne Encephalitis Virus. 2021, 1 .

AMA Style

Niluka Goonawardane, Laura Upstone, Mark Harris, Ian M Jones. Identification of host antiviral genes differentially induced by clinically diverse strains of Tick-Borne Encephalitis Virus. . 2021; ():1.

Chicago/Turabian Style

Niluka Goonawardane; Laura Upstone; Mark Harris; Ian M Jones. 2021. "Identification of host antiviral genes differentially induced by clinically diverse strains of Tick-Borne Encephalitis Virus." , no. : 1.

Journal article
Published: 09 February 2021 in mBio
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Viral interactions during multiple viral infections were examined in Agaricus bisporus cultures harboring 9 viruses (comprising 18 distinct viral RNAs) by statistically analyzing their relative abundance in fruitbodies. Four clusters of viral RNA were identified that suggested synergism and coreplication. Pairwise correlations revealed negative and positive correlations between clusters, indicating further synergisms and an antagonism involving a group containing a putative hypovirus and four nonhost ORFan RNAs (RNAs with no similarity to known sequences) possibly acting as defective interfering RNAs. The disease phenotype was observed in 10 to 15% of the fruitbodies apparently randomly located among asymptomatic fruitbodies. The degree of symptom expression consistently correlated with the levels of the multipartite virus AbV16. Diseased fruitbodies contained very high levels of AbV16 and AbV6 RNA2; these levels were orders of magnitude higher than those in asymptomatic tissues and were shown statistically to be discretely higher populations of abundance, indicating an exponential shift in the replicative capacity of the virus. High levels of AbV16 replication were specific to the fruitbody and not found in the underlying mycelium. There appeared to be a stochastic element occurring in these viral interactions, as observed in the distribution of diseased symptoms across a culture, differences in variance between experiments, and a number of additional viruses undergoing the step-jump in levels between experiments. Possible mechanisms for these multiple and simultaneous viral interactions in single culture are discussed in relation to known virus-host regulatory mechanisms for viral replication and whether additional factors could be considered to account for the 1,000-fold increase in AbV16 and AbV6 RNA2 levels. IMPORTANCE How viruses interact in a multiple-virus infection was examined by quantifying the levels of 18 viral RNAs in fruiting cultures of the agriculturally cultivated fungus Agaricus bisporus and statistically analyzing and modeling their abundance. Synergistic, antagonistic, and neutral interactions occurred simultaneously in cultures. The viral RNAs were grouped into four clusters, each displaying similar relative abundance, and between clusters, further interactions were found with positive, negative, or no correlations. Mushroom fruitbodies showing disease symptoms were distributed apparently randomly across the culture. These symptoms were associated with the presence of viral RNAs from two different clusters at very high levels, 1,000-fold higher than asymptomatic fruitbodies. The role of viral interaction together with stochastic factors and the regulation of host antiviral defenses in pathogenesis are discussed.

ACS Style

Edward Dobbs; Greg Deakin; Julie Bennett; Caoimhe Fleming-Archibald; Ian Jones; Helen Grogan; Kerry Burton. Viral Interactions and Pathogenesis during Multiple Viral Infections in Agaricus bisporus. mBio 2021, 12, 1 .

AMA Style

Edward Dobbs, Greg Deakin, Julie Bennett, Caoimhe Fleming-Archibald, Ian Jones, Helen Grogan, Kerry Burton. Viral Interactions and Pathogenesis during Multiple Viral Infections in Agaricus bisporus. mBio. 2021; 12 (1):1.

Chicago/Turabian Style

Edward Dobbs; Greg Deakin; Julie Bennett; Caoimhe Fleming-Archibald; Ian Jones; Helen Grogan; Kerry Burton. 2021. "Viral Interactions and Pathogenesis during Multiple Viral Infections in Agaricus bisporus." mBio 12, no. 1: 1.

Comment
Published: 02 February 2021 in The Lancet
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Denis Logunov and colleagues1Logunov DY Dolzhikova IV Shcheblyakov DV et al.Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia.Lancet. 2021; (published online Feb 2.)https://doi.org/10.1016/S0140-6736(21)00234-8Summary Full Text Full Text PDF Google Scholar report their interim results from a phase 3 trial of the Sputnik V COVID-19 vaccine in The Lancet. The trial results show a consistent strong protective effect across all participant age groups. Also known as Gam-COVID-Vac, the vaccine uses a heterologous recombinant adenovirus approach using adenovirus 26 (Ad26) and adenovirus 5 (Ad5) as vectors for the expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The use of two varying serotypes, which are given 21 days apart, is intended to overcome any pre-existing adenovirus immunity in the population.2Barouch DH Kik SV Weverling GJ et al.International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations.Vaccine. 2011; 29: 5203-5209Crossref PubMed Scopus (151) Google Scholar Among the major COVID vaccines in development to date, only Gam-COVID-Vac uses this approach; others, such as the Oxford–AstraZeneca vaccine, use the same material for both doses. The earlier vaccine for Ebola virus disease, also developed at Gamaleya National Research Centre for Epidemiology and Microbiology (Moscow, Russia), was similar, with Ad5 and vesicular stomatitis virus as the carrier viruses,3Dolzhikova IV Zubkova OV Tukhvatulin AI et al.Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: an open phase I/II trial in healthy adults in Russia.Hum Vaccin Immunother. 2017; 13: 613-620Crossref PubMed Scopus (45) Google Scholar and the general principle of prime boost with two different vectors has been widely used experimentally.4Lu S Heterologous prime-boost vaccination.Curr Opin Immunol. 2009; 21: 346-351Crossref PubMed Scopus (232) Google Scholar

ACS Style

Ian Jones; Polly Roy. Sputnik V COVID-19 vaccine candidate appears safe and effective. The Lancet 2021, 397, 642 -643.

AMA Style

Ian Jones, Polly Roy. Sputnik V COVID-19 vaccine candidate appears safe and effective. The Lancet. 2021; 397 (10275):642-643.

Chicago/Turabian Style

Ian Jones; Polly Roy. 2021. "Sputnik V COVID-19 vaccine candidate appears safe and effective." The Lancet 397, no. 10275: 642-643.

Journal article
Published: 22 September 2020 in Viruses
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Coronaviruses (CoVs) are enveloped, positive sense, single strand RNA viruses that cause respiratory, intestinal and neurological diseases in mammals and birds. Following replication, CoVs assemble on intracellular membranes including the endoplasmic reticulum Golgi intermediate compartment (ERGIC) where the envelope protein (E) functions in virus assembly and release. In consequence, E potentially contains membrane-modifying peptides. To search for such peptides, the E coding sequence of Mouse Hepatitis Virus (MHV) was inspected for its amino acid conservation, proximity to the membrane and/or predicted amphipathic helices. Peptides identified in silico were synthesized and tested for membrane-modifying activity in the presence of giant unilamellar vesicles (GUVs) consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), sphingomyelin and cholesterol. To confirm the presence of membrane binding peptides identified in the context of a full-length E protein, the wild type and a number of mutants in the putative membrane binding peptide were expressed in Lenti-X-293T mammalian and insect cells, and the distribution of E antigen within the expressing cell was assessed. Our data identify a role for the post-transmembrane region of MHV E in membrane binding.

ACS Style

Entedar A. J. Alsaadi; Benjamin W. Neuman; Ian M. Jones. Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus. Viruses 2020, 12, 1054 .

AMA Style

Entedar A. J. Alsaadi, Benjamin W. Neuman, Ian M. Jones. Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus. Viruses. 2020; 12 (9):1054.

Chicago/Turabian Style

Entedar A. J. Alsaadi; Benjamin W. Neuman; Ian M. Jones. 2020. "Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus." Viruses 12, no. 9: 1054.

Preprint content
Published: 22 May 2020
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The newly emergent SARS-CoV-2 coronavirus is closely related to SARS-CoV which emerged in 2002. Studies on coronaviruses in general, and SARS in particular, have identified the virus spike protein (S) as being central to virus tropism, to the generation of a protective antibody response and to the unambiguous detection of past infections. As a result of this centrality SARS-CoV-2 S protein has a role in many aspects of research from vaccines to diagnostic tests. We describe a number of recombinant forms of SARS-CoV-2 S expressed in commonly available expression systems and their preliminary use in diagnostics and epitope mapping. These sources may find use in the current and future analysis of the virus and the Covid-19 disease it causes.

ACS Style

Sophie M. Jegouic; Silvia Loureiro; Michelle Thom; Deepa Paliwal; Ian M. Jones. Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping. 2020, 1 .

AMA Style

Sophie M. Jegouic, Silvia Loureiro, Michelle Thom, Deepa Paliwal, Ian M. Jones. Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping. . 2020; ():1.

Chicago/Turabian Style

Sophie M. Jegouic; Silvia Loureiro; Michelle Thom; Deepa Paliwal; Ian M. Jones. 2020. "Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping." , no. : 1.

Brief report
Published: 05 September 2019 in Viruses
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Coronaviruses represent current and emerging threats for many species, including humans. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is responsible for sporadic infections in mostly Middle Eastern countries, with occasional transfer elsewhere. A key step in the MERS-CoV replication cycle is the fusion of the virus and host cell membranes mediated by the virus spike protein, S. The location of the fusion peptide within the MERS S protein has not been precisely mapped. We used isolated peptides and giant unilamellar vesicles (GUV) to demonstrate membrane binding for a peptide located near the N-terminus of the S2 domain. Key residues required for activity were mapped by amino acid replacement and their relevance in vitro tested by their introduction into recombinant MERS S protein expressed in mammalian cells. Mutations preventing membrane binding in vitro also abolished S-mediated syncytium formation consistent with the identified peptide acting as the fusion peptide for the S protein of MERS-CoV.

ACS Style

Entedar A. J. Alsaadi; Benjamin W. Neuman; Ian M. Jones. A Fusion Peptide in the Spike Protein of MERS Coronavirus. Viruses 2019, 11, 825 .

AMA Style

Entedar A. J. Alsaadi, Benjamin W. Neuman, Ian M. Jones. A Fusion Peptide in the Spike Protein of MERS Coronavirus. Viruses. 2019; 11 (9):825.

Chicago/Turabian Style

Entedar A. J. Alsaadi; Benjamin W. Neuman; Ian M. Jones. 2019. "A Fusion Peptide in the Spike Protein of MERS Coronavirus." Viruses 11, no. 9: 825.

Review
Published: 01 April 2019 in Future Virology
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Coronaviruses (CoVs) infect many species causing a variety of diseases with a range of severities. Their members include zoonotic viruses with pandemic potential where therapeutic options are currently limited. Despite this diversity CoVs share some common features including the production, in infected cells, of elaborate membrane structures. Membranes represent both an obstacle and aid to CoV replication – and in consequence – virus-encoded structural and nonstructural proteins have membrane-binding properties. The structural proteins encounter cellular membranes at both entry and exit of the virus while the nonstructural proteins reorganize cellular membranes to benefit virus replication. Here, the role of each protein in membrane binding is described to provide a comprehensive picture of their role in the CoV replication cycle.

ACS Style

Entedar A J Alsaadi; Ian M Jones. Membrane binding proteins of coronaviruses. Future Virology 2019, 14, 275 -286.

AMA Style

Entedar A J Alsaadi, Ian M Jones. Membrane binding proteins of coronaviruses. Future Virology. 2019; 14 (4):275-286.

Chicago/Turabian Style

Entedar A J Alsaadi; Ian M Jones. 2019. "Membrane binding proteins of coronaviruses." Future Virology 14, no. 4: 275-286.

Journal article
Published: 25 July 2018 in Wellcome Open Research
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Background: Foot and mouth disease virus (FMDV), a member of the picornaviridae that causes vesicular disease in ungulates, has seven serotypes and a large number of strains, making universal detection challenging. The mature virion is made up of 4 structural proteins, virus protein (VP) 1 – VP4, VP1-VP3 of which form the outer surface of the particle and VP4 largely contained within. Prior to mature virion formation VP2 and VP4 occur together as VP0, a structural component of the pre-capsid which, as a result of containing the internal VP4 sequence, is relatively conserved among all strains and serotypes. Detection of VP0 might therefore represent a universal virus marker. Methods: FMDV virus protein 0 (VP0) was expressed in bacteria as a SUMO fusion protein and the SUMO carrier removed by site specific proteolysis. Rabbit polyvalent sera were generated to the isolated VP0 protein and their reactivity characterised by a number of immunoassays and by epitope mapping on peptide arrays. Results: The specific VP0 serum recognised a variety of FMDV serotypes, as virus and as virus-like-particles, by a variety of assay formats. Epitope mapping showed the predominant epitopes to occur within the unstructured but highly conserved region of the sequence shared among many serotypes. When immunogold stained VLPs were assessed by TEM analysis they revealed exposure of epitopes on the surface of some particles, consistent with particle breathing hitherto reported for some other picornaviruses but not for FMDV. Conclusion: A polyvalent serum based on the VP0 protein of FMDV represents a broadly reactive reagent capable of detection of many if not all FMDV isolates. The suggestion of particle breathing obtained with this serum suggests a reconsideration of the FMDV entry mechanism.

ACS Style

Silvia Loureiro; Claudine Porta; Hemanta K. Maity; Eva Perez; Flavia F. Bagno; Abhay Kotecha; Elizabeth Fry; Jingshan Ren; David I. Stuart; Holger Hoenemann; Amaya Serrano; Erwin Van Den Born; Bryan Charleston; Ian M. Jones. Universal detection of foot and mouth disease virus based on the conserved VP0 protein. Wellcome Open Research 2018, 3, 1 .

AMA Style

Silvia Loureiro, Claudine Porta, Hemanta K. Maity, Eva Perez, Flavia F. Bagno, Abhay Kotecha, Elizabeth Fry, Jingshan Ren, David I. Stuart, Holger Hoenemann, Amaya Serrano, Erwin Van Den Born, Bryan Charleston, Ian M. Jones. Universal detection of foot and mouth disease virus based on the conserved VP0 protein. Wellcome Open Research. 2018; 3 ():1.

Chicago/Turabian Style

Silvia Loureiro; Claudine Porta; Hemanta K. Maity; Eva Perez; Flavia F. Bagno; Abhay Kotecha; Elizabeth Fry; Jingshan Ren; David I. Stuart; Holger Hoenemann; Amaya Serrano; Erwin Van Den Born; Bryan Charleston; Ian M. Jones. 2018. "Universal detection of foot and mouth disease virus based on the conserved VP0 protein." Wellcome Open Research 3, no. : 1.

Journal article
Published: 26 May 2017 in Scientific Reports
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Thirty unique non-host RNAs were sequenced in the cultivated fungus, Agaricus bisporus, comprising 18 viruses each encoding an RdRp domain with an additional 8 ORFans (non-host RNAs with no similarity to known sequences). Two viruses were multipartite with component RNAs showing correlative abundances and common 3' motifs. The viruses, all positive sense single-stranded, were classified into diverse orders/families. Multiple infections of Agaricus may represent a diverse, dynamic and interactive viral ecosystem with sequence variability ranging over 2 orders of magnitude and evidence of recombination, horizontal gene transfer and variable fragment numbers. Large numbers of viral RNAs were detected in multiple Agaricus samples; up to 24 in samples symptomatic for disease and 8-17 in asymptomatic samples, suggesting adaptive strategies for co-existence. The viral composition of growing cultures was dynamic, with evidence of gains and losses depending on the environment and included new hypothetical viruses when compared with the current transcriptome and EST databases. As the non-cellular transmission of mycoviruses is rare, the founding infections may be ancient, preserved in wild Agaricus populations, which act as reservoirs for subsequent cell-to-cell infection when host populations are expanded massively through fungiculture.

ACS Style

Gregory Deakin; Edward Dobbs; Julie M. Bennett; Ian M. Jones; Helen Grogan; Kerry S. Burton. Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing. Scientific Reports 2017, 7, 2469 .

AMA Style

Gregory Deakin, Edward Dobbs, Julie M. Bennett, Ian M. Jones, Helen Grogan, Kerry S. Burton. Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing. Scientific Reports. 2017; 7 (1):2469.

Chicago/Turabian Style

Gregory Deakin; Edward Dobbs; Julie M. Bennett; Ian M. Jones; Helen Grogan; Kerry S. Burton. 2017. "Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing." Scientific Reports 7, no. 1: 2469.

Journal article
Published: 07 March 2017 in Insects
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Deformed wing virus (DWV) in association with Varroa destructor is currently attributed to being responsible for colony collapse in the western honey bee (Apis mellifera). The appearance of deformed individuals within an infested colony has long been associated with colony losses. However, it is unknown why only a fraction of DWV positive bees develop deformed wings. This study concerns two small studies comparing deformed and non-deformed bees. In Brazil, asymptomatic bees (no wing deformity) that had been parasitised by Varroa as pupae had higher DWV loads than non-parasitised bees. However, we found no greater bilateral asymmetry in wing morphology due to DWV titres or parasitisation. As expected, using RT-qPCR, deformed bees were found to contain the highest viral loads. In a separate study, next generation sequencing (NGS) was applied to compare the entire DWV genomes from paired symptomatic and asymptomatic bees from three colonies on two different Hawaiian islands. This revealed no consistent differences between DWV genomes from deformed or asymptomatic bees, with the greatest variation seen between locations, not phenotypes. All samples, except one, were dominated by DWV type A. This small-scale study suggests that there is no unique genetic variant associated with wing deformity; but that many DWV variants have the potential to cause deformity.

ACS Style

Laura E. Brettell; Gideon J. Mordecai; Declan C. Schroeder; Ian M. Jones; Jessica R. Da Silva; Marina Vicente-Rubiano; Stephen Martin. A Comparison of Deformed Wing Virus in Deformed and Asymptomatic Honey Bees. Insects 2017, 8, 28 .

AMA Style

Laura E. Brettell, Gideon J. Mordecai, Declan C. Schroeder, Ian M. Jones, Jessica R. Da Silva, Marina Vicente-Rubiano, Stephen Martin. A Comparison of Deformed Wing Virus in Deformed and Asymptomatic Honey Bees. Insects. 2017; 8 (1):28.

Chicago/Turabian Style

Laura E. Brettell; Gideon J. Mordecai; Declan C. Schroeder; Ian M. Jones; Jessica R. Da Silva; Marina Vicente-Rubiano; Stephen Martin. 2017. "A Comparison of Deformed Wing Virus in Deformed and Asymptomatic Honey Bees." Insects 8, no. 1: 28.

Journal article
Published: 07 October 2016 in Scientific Reports
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There is an increasing global trend of emerging infectious diseases (EIDs) affecting a wide range of species, including honey bees. The global epidemic of the single stranded RNA Deformed wing virus (DWV), driven by the spread of Varroa destructor has been well documented. However, DWV is just one of many insect RNA viruses which infect a wide range of hosts. Here we report the full genome sequence of a novel Iflavirus named Moku virus (MV), discovered in the social wasp Vespula pensylvanica collected in Hawaii. The novel genome is 10,056 nucleotides long and encodes a polyprotein of 3050 amino acids. Phylogenetic analysis showed that MV is most closely related to Slow bee paralysis virus (SBPV), which is highly virulent in honey bees but rarely detected. Worryingly, MV sequences were also detected in honey bees and Varroa from the same location, suggesting that MV can also infect other hymenopteran and Acari hosts.

ACS Style

Gideon J Mordecai; Laura Brettell; Purnima Pachori; Ethel M. Villalobos; Stephen Martin; Ian Jones; Declan Schroeder. Moku virus; a new Iflavirus found in wasps, honey bees and Varroa. Scientific Reports 2016, 6, 34983 .

AMA Style

Gideon J Mordecai, Laura Brettell, Purnima Pachori, Ethel M. Villalobos, Stephen Martin, Ian Jones, Declan Schroeder. Moku virus; a new Iflavirus found in wasps, honey bees and Varroa. Scientific Reports. 2016; 6 (1):34983.

Chicago/Turabian Style

Gideon J Mordecai; Laura Brettell; Purnima Pachori; Ethel M. Villalobos; Stephen Martin; Ian Jones; Declan Schroeder. 2016. "Moku virus; a new Iflavirus found in wasps, honey bees and Varroa." Scientific Reports 6, no. 1: 34983.

Research article
Published: 01 June 2016 in Arteriosclerosis, Thrombosis, and Vascular Biology
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Objective— Thiol isomerases facilitate protein folding in the endoplasmic reticulum, and several of these enzymes, including protein disulfide isomerase and ERp57, are mobilized to the surface of activated platelets, where they influence platelet aggregation, blood coagulation, and thrombus formation. In this study, we examined the synthesis and trafficking of thiol isomerases in megakaryocytes, determined their subcellular localization in platelets, and identified the cellular events responsible for their movement to the platelet surface on activation. Approach and Results— Immunofluorescence microscopy imaging was used to localize protein disulfide isomerase and ERp57 in murine and human megakaryocytes at various developmental stages. Immunofluorescence microscopy and subcellular fractionation analysis were used to localize these proteins in platelets to a compartment distinct from known secretory vesicles that overlaps with an inner cell-surface membrane region defined by the endoplasmic/sarcoplasmic reticulum proteins calnexin and sarco/endoplasmic reticulum calcium ATPase 3. Immunofluorescence microscopy and flow cytometry were used to monitor thiol isomerase mobilization in activated platelets in the presence and absence of actin polymerization (inhibited by latrunculin) and in the presence or absence of membrane fusion mediated by Munc13-4 (absent in platelets from Unc13d Jinx mice). Conclusions— Platelet-borne thiol isomerases are trafficked independently of secretory granule contents in megakaryocytes and become concentrated in a subcellular compartment near the inner surface of the platelet outer membrane corresponding to the sarco/endoplasmic reticulum of these cells. Thiol isomerases are mobilized to the surface of activated platelets via a process that requires actin polymerization but not soluble N-ethylmaleimide–sensitive fusion protein attachment receptor/Munc13-4–dependent vesicular–plasma membrane fusion.

ACS Style

Marilena Crescente; Fred Pluthero; Ling Li; Richard W. Lo; Tony G. Walsh; Michael P. Schenk; Lisa-Marie Holbrook; Silvia Louriero; Marfoua S. Ali; Sakthivel Vaiyapuri; Hervé Falet; Ian M. Jones; Alastair Poole; Walter H.A. Kahr; Jonathan M. Gibbins. Intracellular Trafficking, Localization, and Mobilization of Platelet-Borne Thiol Isomerases. Arteriosclerosis, Thrombosis, and Vascular Biology 2016, 36, 1164 -1173.

AMA Style

Marilena Crescente, Fred Pluthero, Ling Li, Richard W. Lo, Tony G. Walsh, Michael P. Schenk, Lisa-Marie Holbrook, Silvia Louriero, Marfoua S. Ali, Sakthivel Vaiyapuri, Hervé Falet, Ian M. Jones, Alastair Poole, Walter H.A. Kahr, Jonathan M. Gibbins. Intracellular Trafficking, Localization, and Mobilization of Platelet-Borne Thiol Isomerases. Arteriosclerosis, Thrombosis, and Vascular Biology. 2016; 36 (6):1164-1173.

Chicago/Turabian Style

Marilena Crescente; Fred Pluthero; Ling Li; Richard W. Lo; Tony G. Walsh; Michael P. Schenk; Lisa-Marie Holbrook; Silvia Louriero; Marfoua S. Ali; Sakthivel Vaiyapuri; Hervé Falet; Ian M. Jones; Alastair Poole; Walter H.A. Kahr; Jonathan M. Gibbins. 2016. "Intracellular Trafficking, Localization, and Mobilization of Platelet-Borne Thiol Isomerases." Arteriosclerosis, Thrombosis, and Vascular Biology 36, no. 6: 1164-1173.

Observational study
Published: 01 June 2016 in Medicine
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Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder. Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013–June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia. We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE.

ACS Style

Pierre Louge; Mathieu Coulange; Frederic Beneton; Emmanuel Gempp; Olivier Le Pennetier; Maxime Algoud; Lorene Dubourg; Pierre Naibo; Marion Marlinge; Pierre Michelet; Donato Vairo; Nathalie Kipson; François Kerbaul; Yves Jammes; Ian Jones; Jean-Guillaume Steinberg; Jean Ruf; Régis Guieu; Alain Boussuges; Emmanuel Fenouillet. Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness. Medicine 2016, 95, e4060 .

AMA Style

Pierre Louge, Mathieu Coulange, Frederic Beneton, Emmanuel Gempp, Olivier Le Pennetier, Maxime Algoud, Lorene Dubourg, Pierre Naibo, Marion Marlinge, Pierre Michelet, Donato Vairo, Nathalie Kipson, François Kerbaul, Yves Jammes, Ian Jones, Jean-Guillaume Steinberg, Jean Ruf, Régis Guieu, Alain Boussuges, Emmanuel Fenouillet. Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness. Medicine. 2016; 95 (26):e4060.

Chicago/Turabian Style

Pierre Louge; Mathieu Coulange; Frederic Beneton; Emmanuel Gempp; Olivier Le Pennetier; Maxime Algoud; Lorene Dubourg; Pierre Naibo; Marion Marlinge; Pierre Michelet; Donato Vairo; Nathalie Kipson; François Kerbaul; Yves Jammes; Ian Jones; Jean-Guillaume Steinberg; Jean Ruf; Régis Guieu; Alain Boussuges; Emmanuel Fenouillet. 2016. "Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness." Medicine 95, no. 26: e4060.

Brief report
Published: 10 March 2016 in mAbs
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In vivo, enzymatic reduction of some protein disulfide bonds, allosteric disulfide bonds, provides an important level of structural and functional regulation. The free cysteine residues generated can be labeled by maleimide reagents, including biotin derivatives, allowing the reduced protein to be detected or purified. During the screening of monoclonal antibodies for those specific for the reduced forms of proteins, we isolated OX133, a unique antibody that recognizes polypeptide resident, N-ethylmaleimide (NEM)-modified cysteine residues in a sequence-independent manner. OX133 offers an alternative to biotin-maleimide reagents for labeling reduced/alkylated antigens and capturing reduced/alkylated proteins with the advantage that NEM-modified proteins are more easily detected in mass spectrometry, and may be more easily recovered than is the case following capture with biotin based reagents.

ACS Style

Lisa-Marie Holbrook; Lai-Shan Kwong; Clive Metcalfe; Emmanuel Fenouillet; Ian Jones; A. Neil Barclay. OX133, a monoclonal antibody recognizing protein-bound N-ethylmaleimide for the identification of reduced disulfide bonds in proteins. mAbs 2016, 8, 672 -677.

AMA Style

Lisa-Marie Holbrook, Lai-Shan Kwong, Clive Metcalfe, Emmanuel Fenouillet, Ian Jones, A. Neil Barclay. OX133, a monoclonal antibody recognizing protein-bound N-ethylmaleimide for the identification of reduced disulfide bonds in proteins. mAbs. 2016; 8 (4):672-677.

Chicago/Turabian Style

Lisa-Marie Holbrook; Lai-Shan Kwong; Clive Metcalfe; Emmanuel Fenouillet; Ian Jones; A. Neil Barclay. 2016. "OX133, a monoclonal antibody recognizing protein-bound N-ethylmaleimide for the identification of reduced disulfide bonds in proteins." mAbs 8, no. 4: 672-677.

Journal article
Published: 17 November 2015 in The ISME Journal
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Treatment of emerging RNA viruses is hampered by the high mutation and replication rates that enable these viruses to operate as a quasispecies. Declining honey bee populations have been attributed to the ectoparasitic mite Varroa destructor and its affiliation with Deformed Wing Virus (DWV). In the current study we use next-generation sequencing to investigate the DWV quasispecies in an apiary known to suffer from overwintering colony losses. We show that the DWV species complex is made up of three master variants. Our results indicate that a new DWV Type C variant is distinct from the previously described types A and B, but together they form a distinct clade compared with other members of the Iflaviridae. The molecular clock estimation predicts that Type C diverged from the other variants ∼319 years ago. The discovery of a new master variant of DWV has important implications for the positive identification of the true pathogen within global honey bee populations.

ACS Style

Gideon J Mordecai; Lena Wilfert; Stephen Martin; Ian Jones; Declan Schroeder. Diversity in a honey bee pathogen: first report of a third master variant of the Deformed Wing Virus quasispecies. The ISME Journal 2015, 10, 1264 -1273.

AMA Style

Gideon J Mordecai, Lena Wilfert, Stephen Martin, Ian Jones, Declan Schroeder. Diversity in a honey bee pathogen: first report of a third master variant of the Deformed Wing Virus quasispecies. The ISME Journal. 2015; 10 (5):1264-1273.

Chicago/Turabian Style

Gideon J Mordecai; Lena Wilfert; Stephen Martin; Ian Jones; Declan Schroeder. 2015. "Diversity in a honey bee pathogen: first report of a third master variant of the Deformed Wing Virus quasispecies." The ISME Journal 10, no. 5: 1264-1273.

Journal article
Published: 03 November 2015 in The Open Virology Journal
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Epstein-Barr virus (EBV) is classified as a member in the orderherpesvirales, familyherpesviridae, subfamilygammaherpesvirinaeand the genuslymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL).In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies

ACS Style

Abdelwahid Saeed Ali; Mubarak Al-Shraim; Ahmed Musa Al-Hakami; Ian Jones. Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis. The Open Virology Journal 2015, 9, 7 -28.

AMA Style

Abdelwahid Saeed Ali, Mubarak Al-Shraim, Ahmed Musa Al-Hakami, Ian Jones. Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis. The Open Virology Journal. 2015; 9 (1):7-28.

Chicago/Turabian Style

Abdelwahid Saeed Ali; Mubarak Al-Shraim; Ahmed Musa Al-Hakami; Ian Jones. 2015. "Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis." The Open Virology Journal 9, no. 1: 7-28.

Journal article
Published: 27 October 2015 in The ISME Journal
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Over the past 50 years, many millions of European honey bee (Apis mellifera) colonies have died as the ectoparasitic mite, Varroa destructor, has spread around the world. Subsequent studies have indicated that the mite’s association with a group of RNA viral pathogens (Deformed Wing Virus, DWV) correlates with colony death. Here, we propose a phenomenon known as superinfection exclusion that provides an explanation of how certain A. mellifera populations have survived, despite Varroa infestation and high DWV loads. Next-generation sequencing has shown that a non-lethal DWV variant ‘type B’ has become established in these colonies and that the lethal ‘type A’ DWV variant fails to persist in the bee population. We propose that this novel stable host-pathogen relationship prevents the accumulation of lethal variants, suggesting that this interaction could be exploited for the development of an effective treatment that minimises colony losses in the future.

ACS Style

Gideon J Mordecai; Laura Brettell; Stephen Martin; David Dixon; Ian Jones; Declan Schroeder. Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies. The ISME Journal 2015, 10, 1182 -1191.

AMA Style

Gideon J Mordecai, Laura Brettell, Stephen Martin, David Dixon, Ian Jones, Declan Schroeder. Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies. The ISME Journal. 2015; 10 (5):1182-1191.

Chicago/Turabian Style

Gideon J Mordecai; Laura Brettell; Stephen Martin; David Dixon; Ian Jones; Declan Schroeder. 2015. "Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies." The ISME Journal 10, no. 5: 1182-1191.