This page has only limited features, please log in for full access.
Depurination is a frequent modification to both DNA and RNA, in DNA causing point mutations through misincorporation, in RNA, disabling ribosomes and halting protein synthesis. Some modifications of nucleic acids can be determined by direct sequencing using Oxford Nanopore Technologies (ONT). However, the identification of modifications is often limited by noise and their variety and number. Ricin is a toxin which enters cells and depurinates an adenine base in the sarcin-ricin loop of the large ribosomal subunit. This leaves only a ribose backbone, thus inhibiting protein translation. In humans, biological threat agents and ribosome inactivating proteins, such as ricin and saporin, depurinate base 4605 on the 28S rRNA providing a single defined target to try and identify. We postulated that the depurination event could be detected using ONT direct RNA sequencing through a change in charge in the ricin loop. A software tool was developed, RIPpore, that quantified the adenine modification from direct RNA sequencing data of ribosomal RNA purified from respiratory epithelial cells exposed to ricin. This provided a novel method of directly identifying ricin exposure and a basis for the utility of ONT in detecting lesions in nucleic acids caused by depurination events.
Yan Ryan; Abbie Jasmine Harrison; Hannah Trivett; Catherine Hartley; Jonathan David; Graeme Clark; Julian Alexander Hiscox. Using Oxford Nanopore Technology direct RNA sequencing to identify depurination events induced by ricin and other ribosome inactivating proteins. 2021, 1 .
AMA StyleYan Ryan, Abbie Jasmine Harrison, Hannah Trivett, Catherine Hartley, Jonathan David, Graeme Clark, Julian Alexander Hiscox. Using Oxford Nanopore Technology direct RNA sequencing to identify depurination events induced by ricin and other ribosome inactivating proteins. . 2021; ():1.
Chicago/Turabian StyleYan Ryan; Abbie Jasmine Harrison; Hannah Trivett; Catherine Hartley; Jonathan David; Graeme Clark; Julian Alexander Hiscox. 2021. "Using Oxford Nanopore Technology direct RNA sequencing to identify depurination events induced by ricin and other ribosome inactivating proteins." , no. : 1.
The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has triggered a worldwide health emergency. Here, we show that ferritin-like Dps from hyperthermophilic Sulfolobus islandicus, covalently coupled with SARS-CoV-2 antigens via the SpyCatcher system, forms stable multivalent dodecameric vaccine nanoparticles that remain intact even after lyophilisation. Immunisation experiments in mice demonstrated that the SARS-CoV-2 receptor binding domain (RBD) coupled to Dps (RBD-S-Dps) elicited a higher antibody titre and an enhanced neutralising antibody response compared to monomeric RBD. A single immunisation with RBD-S-Dps completely protected hACE2-expressing mice from serious illness and led to viral clearance from the lungs upon SARS-CoV-2 infection. Our data highlight that multimerised SARS-CoV-2 subunit vaccines are a highly efficacious modality, particularly when combined with an ultra-stable scaffold.
Ralf Salzer; Jordan J. Clark; Marina Vaysburd; Veronica T. Chang; Anna Albecka; Leo Kiss; Parul Sharma; Andres Gonzalez Llamazares; Anja Kipar; Julian A. Hiscox; Andrew Owen; A. Radu Aricescu; James P. Stewart; Leo C. James; Jan Löwe. Single‐dose immunisation with a multimerised SARS‐CoV‐2 receptor binding domain (RBD) induces an enhanced and protective response in mice. FEBS Letters 2021, 1 .
AMA StyleRalf Salzer, Jordan J. Clark, Marina Vaysburd, Veronica T. Chang, Anna Albecka, Leo Kiss, Parul Sharma, Andres Gonzalez Llamazares, Anja Kipar, Julian A. Hiscox, Andrew Owen, A. Radu Aricescu, James P. Stewart, Leo C. James, Jan Löwe. Single‐dose immunisation with a multimerised SARS‐CoV‐2 receptor binding domain (RBD) induces an enhanced and protective response in mice. FEBS Letters. 2021; ():1.
Chicago/Turabian StyleRalf Salzer; Jordan J. Clark; Marina Vaysburd; Veronica T. Chang; Anna Albecka; Leo Kiss; Parul Sharma; Andres Gonzalez Llamazares; Anja Kipar; Julian A. Hiscox; Andrew Owen; A. Radu Aricescu; James P. Stewart; Leo C. James; Jan Löwe. 2021. "Single‐dose immunisation with a multimerised SARS‐CoV‐2 receptor binding domain (RBD) induces an enhanced and protective response in mice." FEBS Letters , no. : 1.
This article provides a brief overview of drug resistance to antiviral therapy as well as known and emergent variability in key SARS-CoV-2 viral sequences. The purpose is to stimulate deliberation about the need to consider drug resistance prior to widespread roll-out of antivirals for SARS-CoV-2. Many existing candidate agents have mechanisms of action involving drug targets likely to be critical for future drug development. Resistance emerged quickly with monotherapies deployed for other pulmonary viruses such as influenza virus, and in HIV mutations in key drug targets compromised efficacy of multiple drugs within a class. The potential for drug resistance in SARS-CoV-2 has not yet been rigorously debated or assessed, and we call for more academic and industry research on this potentially important future threat prior to widespread roll-out of monotherapies for COVID-19 treatment and prevention.
Julian A Hiscox; Saye H Khoo; James P Stewart; Andrew Owen. Shutting the gate before the horse has bolted: is it time for a conversation about SARS-CoV-2 and antiviral drug resistance? Journal of Antimicrobial Chemotherapy 2021, 1 .
AMA StyleJulian A Hiscox, Saye H Khoo, James P Stewart, Andrew Owen. Shutting the gate before the horse has bolted: is it time for a conversation about SARS-CoV-2 and antiviral drug resistance? Journal of Antimicrobial Chemotherapy. 2021; ():1.
Chicago/Turabian StyleJulian A Hiscox; Saye H Khoo; James P Stewart; Andrew Owen. 2021. "Shutting the gate before the horse has bolted: is it time for a conversation about SARS-CoV-2 and antiviral drug resistance?" Journal of Antimicrobial Chemotherapy , no. : 1.
The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has triggered a worldwide health emergency. So far, several different types of vaccines have shown strong efficacy. However, both the emergence of new SARS-CoV-2 variants and the need to vaccinate a large fraction of the world’s population necessitate the development of alternative vaccines, especially those that are simple and easy to store, transport and administer. Here, we showed that ferritin-like Dps protein from hyperthermophilic Sulfolobus islandicus can be covalently coupled with different SARS-CoV-2 antigens via the SpyCatcher system, to form extremely stable and defined multivalent dodecameric vaccine nanoparticles that remain intact even after lyophilisation. Immunisation experiments in mice demonstrated that the SARS-CoV-2 receptor binding domain (RBD) coupled to Dps (RBD-S-Dps) shows particular promise as it elicited a higher antibody titre and an enhanced neutralising antibody response compared to the monomeric RBD. Furthermore, we showed that a single immunisation with the multivalent RBD-S-Dps completely protected hACE2-expressing mice from serious illness and led to efficient viral clearance from the lungs upon SARS-CoV-2 infection. Our data highlight that multimerised SARS-CoV-2 subunit vaccines are a highly efficacious modality, particularly when combined with an ultra-stable scaffold.
Ralf Salzer; Jordan J. Clark; Marina Vaysburd; Veronica T. Chang; Anna Albecka; Leo Kiss; Parul Sharma; Andres Gonzalez Llamazares; Anja Kipar; Julian A. Hiscox; Andrew Owen; A. Radu Aricescu; James P. Stewart; Leo C. James; Jan Löwe. Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice. 2021, 1 .
AMA StyleRalf Salzer, Jordan J. Clark, Marina Vaysburd, Veronica T. Chang, Anna Albecka, Leo Kiss, Parul Sharma, Andres Gonzalez Llamazares, Anja Kipar, Julian A. Hiscox, Andrew Owen, A. Radu Aricescu, James P. Stewart, Leo C. James, Jan Löwe. Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice. . 2021; ():1.
Chicago/Turabian StyleRalf Salzer; Jordan J. Clark; Marina Vaysburd; Veronica T. Chang; Anna Albecka; Leo Kiss; Parul Sharma; Andres Gonzalez Llamazares; Anja Kipar; Julian A. Hiscox; Andrew Owen; A. Radu Aricescu; James P. Stewart; Leo C. James; Jan Löwe. 2021. "Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice." , no. : 1.
SARS-CoV-2 is thought to have originated in the human population from a zoonotic spillover event. Infection in humans results in a variety of outcomes ranging from asymptomatic cases to the disease COVID-19, which can have significant morbidity and mortality, with over two million confirmed deaths worldwide as of January 2021. Over a year into the pandemic, sequencing analysis has shown that variants of SARS-CoV-2 are being selected as the virus continues to circulate widely within the human population. The predominant drivers of genetic variation within SARS-CoV-2 are single nucleotide polymorphisms (SNPs) caused by polymerase error, potential host factor driven RNA modification, and insertion/deletions (indels) resulting from the discontinuous nature of viral RNA synthesis. While many mutations represent neutral ‘genetic drift’ or have quickly died out, a subset may be affecting viral traits such as transmissibility, pathogenicity, host range, and antigenicity of the virus. In this review, we summarise the current extent of genetic change in SARS-CoV-2, particularly recently emerging variants of concern, and consider the phenotypic consequences of this viral evolution that may impact the future trajectory of the pandemic.
Thomas P. Peacock; Rebekah Penrice-Randal; Julian A. Hiscox; Wendy S. Barclay. SARS-CoV-2 one year on: evidence for ongoing viral adaptation. Journal of General Virology 2021, 102, 001584 .
AMA StyleThomas P. Peacock, Rebekah Penrice-Randal, Julian A. Hiscox, Wendy S. Barclay. SARS-CoV-2 one year on: evidence for ongoing viral adaptation. Journal of General Virology. 2021; 102 (4):001584.
Chicago/Turabian StyleThomas P. Peacock; Rebekah Penrice-Randal; Julian A. Hiscox; Wendy S. Barclay. 2021. "SARS-CoV-2 one year on: evidence for ongoing viral adaptation." Journal of General Virology 102, no. 4: 001584.
We have the tools to track variants and adapt vaccines as required
Alistair C Darby; Julian A Hiscox. Covid-19: variants and vaccination. BMJ 2021, 372, n771 .
AMA StyleAlistair C Darby, Julian A Hiscox. Covid-19: variants and vaccination. BMJ. 2021; 372 ():n771.
Chicago/Turabian StyleAlistair C Darby; Julian A Hiscox. 2021. "Covid-19: variants and vaccination." BMJ 372, no. : n771.
Rationale: In life-threatening Covid-19, corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of SARS-CoV-2 or an independent immunopathologic process is unknown. Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses, and the relationships between viral presence, inflammation, and organ injury. Methods: Tissue was acquired from eleven detailed post-mortem examinations. SARS-CoV-2 organotropism was mapped by multiplex PCR and sequencing, with cellular resolution achieved by in situ viral spike protein detection. Histological evidence of inflammation was quantified from 37 anatomical sites, and the pulmonary immune response characterized by multiplex immunofluorescence. Measurements and Main Results: Multiple aberrant immune responses in fatal Covid-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein, both between and within tissues. An arteritis was identified in the lung, which was further characterised as a monocyte/myeloid-rich vasculitis, and occurred along with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticulo-endothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues. Conclusions: Tissue-specific immunopathology occurs in Covid-19, implicating a significant component of immune-mediated, virus-independent immunopathology as a primary mechanism in severe disease. Our data highlight novel immunopathological mechanisms, and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma cell responses as well as promoting pathogen tolerance in Covid-19. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)
David A. Dorward; Clark D. Russell; In Hwa Um; Mustafa Elshani; Stuart D. Armstrong; Rebekah Penrice-Randal; Tracey Millar; Chris E. B. Lerpiniere; Giulia Tagliavini; Catherine S. Hartley; Nadine P. Randle; Naomi N. Gachanja; Philippe M. D. Potey; Xiaofeng Dong; Alison M. Anderson; Victoria L. Campbell; Alasdair J. Duguid; Wael Al Qsous; Ralph BouHaidar; J. Kenneth Baillie; Kevin Dhaliwal; William A. Wallace; Christopher O. C. Bellamy; Sandrine Prost; Colin Smith; Julian A. Hiscox; David J. Harrison; Christopher D. Lucas. Tissue-Specific Immunopathology in Fatal COVID-19. American Journal of Respiratory and Critical Care Medicine 2021, 203, 192 -201.
AMA StyleDavid A. Dorward, Clark D. Russell, In Hwa Um, Mustafa Elshani, Stuart D. Armstrong, Rebekah Penrice-Randal, Tracey Millar, Chris E. B. Lerpiniere, Giulia Tagliavini, Catherine S. Hartley, Nadine P. Randle, Naomi N. Gachanja, Philippe M. D. Potey, Xiaofeng Dong, Alison M. Anderson, Victoria L. Campbell, Alasdair J. Duguid, Wael Al Qsous, Ralph BouHaidar, J. Kenneth Baillie, Kevin Dhaliwal, William A. Wallace, Christopher O. C. Bellamy, Sandrine Prost, Colin Smith, Julian A. Hiscox, David J. Harrison, Christopher D. Lucas. Tissue-Specific Immunopathology in Fatal COVID-19. American Journal of Respiratory and Critical Care Medicine. 2021; 203 (2):192-201.
Chicago/Turabian StyleDavid A. Dorward; Clark D. Russell; In Hwa Um; Mustafa Elshani; Stuart D. Armstrong; Rebekah Penrice-Randal; Tracey Millar; Chris E. B. Lerpiniere; Giulia Tagliavini; Catherine S. Hartley; Nadine P. Randle; Naomi N. Gachanja; Philippe M. D. Potey; Xiaofeng Dong; Alison M. Anderson; Victoria L. Campbell; Alasdair J. Duguid; Wael Al Qsous; Ralph BouHaidar; J. Kenneth Baillie; Kevin Dhaliwal; William A. Wallace; Christopher O. C. Bellamy; Sandrine Prost; Colin Smith; Julian A. Hiscox; David J. Harrison; Christopher D. Lucas. 2021. "Tissue-Specific Immunopathology in Fatal COVID-19." American Journal of Respiratory and Critical Care Medicine 203, no. 2: 192-201.
Background Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013–2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient—perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD. Methods Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood. Results The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a ‘fatal’ outcome to a ‘survival’ outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence—such as defective interfering genomes. Conclusions The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.
Andrew Bosworth; Natasha Y. Rickett; Xiaofeng Dong; Lisa F. P. Ng; Isabel García-Dorival; David A. Matthews; Tom Fletcher; Michael Jacobs; Emma C. Thomson; Miles W. Carroll; Julian A. Hiscox. Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care. Genome Medicine 2021, 13, 1 -18.
AMA StyleAndrew Bosworth, Natasha Y. Rickett, Xiaofeng Dong, Lisa F. P. Ng, Isabel García-Dorival, David A. Matthews, Tom Fletcher, Michael Jacobs, Emma C. Thomson, Miles W. Carroll, Julian A. Hiscox. Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care. Genome Medicine. 2021; 13 (1):1-18.
Chicago/Turabian StyleAndrew Bosworth; Natasha Y. Rickett; Xiaofeng Dong; Lisa F. P. Ng; Isabel García-Dorival; David A. Matthews; Tom Fletcher; Michael Jacobs; Emma C. Thomson; Miles W. Carroll; Julian A. Hiscox. 2021. "Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care." Genome Medicine 13, no. 1: 1-18.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses the viral spike (S) protein for host cell attachment and entry. The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. Cleavage of S generates a polybasic Arg-Arg-Ala-Arg carboxyl-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that binds to cell surface neuropilin-1 (NRP1) and NRP2 receptors. We used x-ray crystallography and biochemical approaches to show that the S1 CendR motif directly bound NRP1. Blocking this interaction by RNA interference or selective inhibitors reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection and may potentially provide a therapeutic target for COVID-19.
James L. Daly; Boris Simonetti; Katja Klein; Kai-En Chen; Maia Kavanagh Williamson; Carlos Antón-Plágaro; Deborah K. Shoemark; Lorena Simón-Gracia; Michael Bauer; Reka Hollandi; Urs F. Greber; Peter Horvath; Richard B. Sessions; Ari Helenius; Julian A. Hiscox; Tambet Teesalu; David A. Matthews; Andrew D. Davidson; Brett M. Collins; Peter J. Cullen; Yohei Yamauchi. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 2020, 370, 861 -865.
AMA StyleJames L. Daly, Boris Simonetti, Katja Klein, Kai-En Chen, Maia Kavanagh Williamson, Carlos Antón-Plágaro, Deborah K. Shoemark, Lorena Simón-Gracia, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter Horvath, Richard B. Sessions, Ari Helenius, Julian A. Hiscox, Tambet Teesalu, David A. Matthews, Andrew D. Davidson, Brett M. Collins, Peter J. Cullen, Yohei Yamauchi. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science. 2020; 370 (6518):861-865.
Chicago/Turabian StyleJames L. Daly; Boris Simonetti; Katja Klein; Kai-En Chen; Maia Kavanagh Williamson; Carlos Antón-Plágaro; Deborah K. Shoemark; Lorena Simón-Gracia; Michael Bauer; Reka Hollandi; Urs F. Greber; Peter Horvath; Richard B. Sessions; Ari Helenius; Julian A. Hiscox; Tambet Teesalu; David A. Matthews; Andrew D. Davidson; Brett M. Collins; Peter J. Cullen; Yohei Yamauchi. 2020. "Neuropilin-1 is a host factor for SARS-CoV-2 infection." Science 370, no. 6518: 861-865.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Sequencing the viral genome as the outbreak progresses is important, particularly in the identification of emerging isolates with different pathogenic potential and to identify whether nucleotide changes in the genome will impair clinical diagnostic tools such as real-time PCR assays. Although single nucleotide polymorphisms and point mutations occur during the replication of coronaviruses, one of the biggest drivers in genetic change is recombination. This can manifest itself in insertions and/or deletions in the viral genome. Therefore, sequencing strategies that underpin molecular epidemiology and inform virus biology in patients should take these factors into account. A long amplicon/read length-based RT-PCR sequencing approach focused on the Oxford Nanopore MinION/GridION platforms was developed to identify and sequence the SARS-CoV-2 genome in samples from patients with or suspected of COVID-19. The protocol, termed Rapid Sequencing Long Amplicons (RSLAs) used random primers to generate cDNA from RNA purified from a sample from a patient, followed by single or multiplex PCRs to generate longer amplicons of the viral genome. The base protocol was used to identify SARS-CoV-2 in a variety of clinical samples and proved sensitive in identifying viral RNA in samples from patients that had been declared negative using other nucleic acid-based assays (false negative). Sequencing the amplicons revealed that a number of patients had a proportion of viral genomes with deletions.
Shona C. Moore; Rebekah Penrice-Randall; Muhannad Alruwaili; Nadine Randle; Stuart Armstrong; Catherine Hartley; Sam Haldenby; Xiaofeng Dong; Abdulrahman Alrezaihi; Mai Almsaud; Eleanor Bentley; Jordan Clark; Isabel García-Dorival; Paul Gilmore; Ximeng Han; Benjamin Jones; Lisa Luu; Parul Sharma; Ghada Shawli; Yani Sun; Qin Zhao; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Jake Dunning; En-Min Zhou; Tom Solomon; Michael Beadsworth; James Cruise; Derrick W. Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard Vipond; Lisa Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; James Stewart; Alistair Darby; Malcolm Semple; Lance Turtle; Julian A. Hiscox. Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism. Viruses 2020, 12, 1164 .
AMA StyleShona C. Moore, Rebekah Penrice-Randall, Muhannad Alruwaili, Nadine Randle, Stuart Armstrong, Catherine Hartley, Sam Haldenby, Xiaofeng Dong, Abdulrahman Alrezaihi, Mai Almsaud, Eleanor Bentley, Jordan Clark, Isabel García-Dorival, Paul Gilmore, Ximeng Han, Benjamin Jones, Lisa Luu, Parul Sharma, Ghada Shawli, Yani Sun, Qin Zhao, Steven T. Pullan, Daniel P. Carter, Kevin Bewley, Jake Dunning, En-Min Zhou, Tom Solomon, Michael Beadsworth, James Cruise, Derrick W. Crook, David A. Matthews, Andrew D. Davidson, Zana Mahmood, Waleed Aljabr, Julian Druce, Richard Vipond, Lisa Ng, Laurent Renia, Peter J. M. Openshaw, J. Kenneth Baillie, Miles W. Carroll, James Stewart, Alistair Darby, Malcolm Semple, Lance Turtle, Julian A. Hiscox. Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism. Viruses. 2020; 12 (10):1164.
Chicago/Turabian StyleShona C. Moore; Rebekah Penrice-Randall; Muhannad Alruwaili; Nadine Randle; Stuart Armstrong; Catherine Hartley; Sam Haldenby; Xiaofeng Dong; Abdulrahman Alrezaihi; Mai Almsaud; Eleanor Bentley; Jordan Clark; Isabel García-Dorival; Paul Gilmore; Ximeng Han; Benjamin Jones; Lisa Luu; Parul Sharma; Ghada Shawli; Yani Sun; Qin Zhao; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Jake Dunning; En-Min Zhou; Tom Solomon; Michael Beadsworth; James Cruise; Derrick W. Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard Vipond; Lisa Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; James Stewart; Alistair Darby; Malcolm Semple; Lance Turtle; Julian A. Hiscox. 2020. "Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism." Viruses 12, no. 10: 1164.
COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2, a recently emerged coronavirus that has rapidly caused a pandemic. Coalescence of a second wave of this virus with seasonal respiratory viruses, particularly influenza virus is a possible global health concern. To investigate this, transgenic mice expressing the human ACE2 receptor driven by the epithelial cell cytokeratin-18 gene promoter (K18-hACE2) were first infected with IAV followed by SARS-CoV-2. The host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 only. Infection of mice with each individual virus resulted in a disease phenotype compared to control mice. Although SARS-CoV-2 RNA synthesis appeared significantly reduced in the sequentially infected mice, these mice had a more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to singly infected or control mice. The sequential infection also exacerbated the extrapulmonary manifestations associated with SARS-CoV-2. This included a more severe encephalitis. Taken together, the data suggest that the concept of ‘twinfection’ is deleterious and mitigation steps should be instituted as part of a comprehensive public health response to the COVID-19 pandemic.
Jordan J. Clark; Rebekah Penrice-Randal; Parul Sharma; Anja Kipar; Xiaofeng Dong; Shaun H. Pennington; Amy E. Marriott; Stefano Colombo; Andrew Davidson; Maia Kavanagh Williamson; David A. Matthews; Lance Turtle; Tessa Prince; Grant L. Hughes; Edward I. Patterson; Ghada Shawli; Krishanthi Subramaniam; Jo Sharp; Lynn McLaughlin; En-Min Zhou; Joseph D. Turner; Giancarlo Biagini; Andrew Owen; Julian A. Hiscox; James P. Stewart. Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19. 2020, 1 .
AMA StyleJordan J. Clark, Rebekah Penrice-Randal, Parul Sharma, Anja Kipar, Xiaofeng Dong, Shaun H. Pennington, Amy E. Marriott, Stefano Colombo, Andrew Davidson, Maia Kavanagh Williamson, David A. Matthews, Lance Turtle, Tessa Prince, Grant L. Hughes, Edward I. Patterson, Ghada Shawli, Krishanthi Subramaniam, Jo Sharp, Lynn McLaughlin, En-Min Zhou, Joseph D. Turner, Giancarlo Biagini, Andrew Owen, Julian A. Hiscox, James P. Stewart. Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19. . 2020; ():1.
Chicago/Turabian StyleJordan J. Clark; Rebekah Penrice-Randal; Parul Sharma; Anja Kipar; Xiaofeng Dong; Shaun H. Pennington; Amy E. Marriott; Stefano Colombo; Andrew Davidson; Maia Kavanagh Williamson; David A. Matthews; Lance Turtle; Tessa Prince; Grant L. Hughes; Edward I. Patterson; Ghada Shawli; Krishanthi Subramaniam; Jo Sharp; Lynn McLaughlin; En-Min Zhou; Joseph D. Turner; Giancarlo Biagini; Andrew Owen; Julian A. Hiscox; James P. Stewart. 2020. "Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19." , no. : 1.
Background Viral load is a major contributor to outcome in patients with Ebola virus disease (EVD), with high values leading to a fatal outcome. Evidence from the 2013–2016 Ebola virus (EBOV) outbreak indicated that different genotypes of the virus can have different phenotypes in patients. Additionally, due to the error-prone nature of viral RNA synthesis in an individual patient, the EBOV genome exists around a dominant viral genome sequence. The minor variants within a patient may contribute to the overall phenotype in terms of viral protein function. To investigate the effects of these minor variants, blood samples from patients with acute EVD were deeply sequenced. Results We examine the minor variant frequency between patients with acute EVD who survived infection with those who died. Non-synonymous differences in viral proteins were identified that have implications for viral protein function. The greatest frequency of substitution was identified at three codon sites in the L gene—which encodes the viral RNA-dependent RNA polymerase (RdRp). Recapitulating this in an assay for virus replication, these substitutions result in aberrant viral RNA synthesis and correlate with patient outcome. Conclusions Together, these findings support the notion that in patients who survived EVD, in some cases, the genetic variability of the virus resulted in deleterious mutations that affected viral protein function, leading to reduced viral load. Such mutations may also lead to persistent strains of the virus and be associated with recrudescent infections.
Xiaofeng Dong; Jordana Munoz-Basagoiti; Natasha Y. Rickett; Georgios Pollakis; William A. Paxton; Stephan Günther; Romy Kerber; Lisa F. P. Ng; Michael J. Elmore; N’Faly Magassouba; Miles W. Carroll; David A. Matthews; Julian A. Hiscox. Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease. Genome Biology 2020, 21, 1 -20.
AMA StyleXiaofeng Dong, Jordana Munoz-Basagoiti, Natasha Y. Rickett, Georgios Pollakis, William A. Paxton, Stephan Günther, Romy Kerber, Lisa F. P. Ng, Michael J. Elmore, N’Faly Magassouba, Miles W. Carroll, David A. Matthews, Julian A. Hiscox. Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease. Genome Biology. 2020; 21 (1):1-20.
Chicago/Turabian StyleXiaofeng Dong; Jordana Munoz-Basagoiti; Natasha Y. Rickett; Georgios Pollakis; William A. Paxton; Stephan Günther; Romy Kerber; Lisa F. P. Ng; Michael J. Elmore; N’Faly Magassouba; Miles W. Carroll; David A. Matthews; Julian A. Hiscox. 2020. "Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease." Genome Biology 21, no. 1: 1-20.
Genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly important to monitor the transmission and adaptive evolution of the virus. The accessibility of high-throughput methods and polymerase chain reaction (PCR) has facilitated a growing ecosystem of protocols. Two differing protocols are tiling multiplex PCR and bait capture enrichment. Each method has advantages and disadvantages but a direct comparison with different viral RNA concentrations has not been performed to assess the performance of these approaches. Here we compare Liverpool amplification, ARTIC amplification, and bait capture using clinical diagnostics samples. All libraries were sequenced using an Illumina MiniSeq with data analyzed using a standardized bioinformatics workflow (SARS-CoV-2 Illumina GeNome Assembly Line; SIGNAL). One sample showed poor SARS-CoV-2 genome coverage and consensus, reflective of low viral RNA concentration. In contrast, the second sample had a higher viral RNA concentration, which yielded good genome coverage and consensus. ARTIC amplification showed the highest depth of coverage results for both samples, suggesting this protocol is effective for low concentrations. Liverpool amplification provided a more even read coverage of the SARS-CoV-2 genome, but at a lower depth of coverage. Bait capture enrichment of SARS-CoV-2 cDNA provided results on par with amplification. While only two clinical samples were examined in this comparative analysis, both the Liverpool and ARTIC amplification methods showed differing efficacy for high and low concentration samples. In addition, amplification-free bait capture enriched sequencing of cDNA is a viable method for generating a SARS-CoV-2 genome sequence and for identification of amplification artifacts.
Jalees A. Nasir; Robert A. Kozak; Patryk Aftanas; Amogelang R. Raphenya; Kendrick M. Smith; Finlay Maguire; Hassaan Maan; Muhannad Alruwaili; Arinjay Banerjee; Hamza Mbareche; Brian P. Alcock; Natalie C. Knox; Karen Mossman; Bo Wang; Julian A. Hiscox; Andrew G. McArthur; Samira Mubareka. A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture. Viruses 2020, 12, 895 .
AMA StyleJalees A. Nasir, Robert A. Kozak, Patryk Aftanas, Amogelang R. Raphenya, Kendrick M. Smith, Finlay Maguire, Hassaan Maan, Muhannad Alruwaili, Arinjay Banerjee, Hamza Mbareche, Brian P. Alcock, Natalie C. Knox, Karen Mossman, Bo Wang, Julian A. Hiscox, Andrew G. McArthur, Samira Mubareka. A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture. Viruses. 2020; 12 (8):895.
Chicago/Turabian StyleJalees A. Nasir; Robert A. Kozak; Patryk Aftanas; Amogelang R. Raphenya; Kendrick M. Smith; Finlay Maguire; Hassaan Maan; Muhannad Alruwaili; Arinjay Banerjee; Hamza Mbareche; Brian P. Alcock; Natalie C. Knox; Karen Mossman; Bo Wang; Julian A. Hiscox; Andrew G. McArthur; Samira Mubareka. 2020. "A Comparison of Whole Genome Sequencing of SARS-CoV-2 Using Amplicon-Based Sequencing, Random Hexamers, and Bait Capture." Viruses 12, no. 8: 895.
Background Tissue inflammation is associated with organ dysfunction and death in Covid-19. The efficacy of dexamethasone in preventing mortality in critical Covid-19 suggests that inflammation has a causal role in death. Whether this deleterious inflammation is a direct response to the presence of SARS-CoV-2, or an independent immuno-pathologic process, is unknown. Methods Tissue was acquired from detailed post-mortem examinations conducted on 11 well characterised hospitalised patients with fatal Covid-19. SARS-CoV-2 organotropism was mapped at an organ level by multiplex PCR and sequencing, with cellular resolution achieved by in situ viral spike (S) protein detection. Histological evidence of inflammation and organ injury was systematically examined, and the pulmonary immune response characterized with multiplex immunofluorescence. Findings SARS-CoV-2 was detected across a wide variety of organs, most frequently in the respiratory tract but also in numerous extra-pulmonary sites. Minimal histological evidence of inflammation was identified in non-pulmonary organs despite frequent detection of viral RNA and protein. At a cellular level, viral protein was identified without adjacent inflammation in the intestine, liver and kidney. Severe inflammatory change was restricted to the lung and reticulo-endothelial system. Diffuse alveolar damage, pulmonary thrombi and a monocyte/myeloid-predominant vasculitis were the predominant pulmonary findings, though there was not a consistent association between viral presence and either the presence or nature of the inflammatory response within the lung. Immunophenotyping revealed an influx of macrophages, monocytes and T cells into pulmonary parenchyma. Bone marrow examination revealed plasmacytosis, erythroid dysplasia and iron-laden macrophages. Plasma cell excess was also present in lymph node, spleen and lung. These stereotyped reticulo-endothelial responses occurred largely independently of the presence of virus in lymphoid tissues. Conclusions Tissue inflammation and organ dysfunction in fatal Covid-19 do not map to the tissue and cellular distribution of SARS-CoV-2, demonstrating tissue-specific tolerance. We conclude that death in Covid-19 is primarily a consequence of immune-mediated, rather than pathogen-mediated, organ inflammation and injury. Funding The Chief Scientist Office, LifeArc, Medical Research Scotland, UKRI (MRC).
David A Dorward; Clark D Russell; In Hwa Um; Mustafa Elshani; Stuart D Armstrong; Rebekah Penrice-Randal; Tracey Millar; Chris Eb Lerpiniere; Giulia Tagliavini; Catherine S Hartley; Nadine P Randall; Naomi N Gachanja; Philippe Md Potey; Alison M Anderson; Victoria L Campbell; Alasdair J Duguid; Wael Al Qsous; Ralph Bouhaidar; J Kenneth Baillie; Kevin Dhaliwal; William A Wallace; Christopher Oc Bellamy; Sandrine Prost; Colin Smith; Julian A Hiscox; David J Harrison; Christopher D Lucas. Tissue-specific tolerance in fatal Covid-19. 2020, 1 .
AMA StyleDavid A Dorward, Clark D Russell, In Hwa Um, Mustafa Elshani, Stuart D Armstrong, Rebekah Penrice-Randal, Tracey Millar, Chris Eb Lerpiniere, Giulia Tagliavini, Catherine S Hartley, Nadine P Randall, Naomi N Gachanja, Philippe Md Potey, Alison M Anderson, Victoria L Campbell, Alasdair J Duguid, Wael Al Qsous, Ralph Bouhaidar, J Kenneth Baillie, Kevin Dhaliwal, William A Wallace, Christopher Oc Bellamy, Sandrine Prost, Colin Smith, Julian A Hiscox, David J Harrison, Christopher D Lucas. Tissue-specific tolerance in fatal Covid-19. . 2020; ():1.
Chicago/Turabian StyleDavid A Dorward; Clark D Russell; In Hwa Um; Mustafa Elshani; Stuart D Armstrong; Rebekah Penrice-Randal; Tracey Millar; Chris Eb Lerpiniere; Giulia Tagliavini; Catherine S Hartley; Nadine P Randall; Naomi N Gachanja; Philippe Md Potey; Alison M Anderson; Victoria L Campbell; Alasdair J Duguid; Wael Al Qsous; Ralph Bouhaidar; J Kenneth Baillie; Kevin Dhaliwal; William A Wallace; Christopher Oc Bellamy; Sandrine Prost; Colin Smith; Julian A Hiscox; David J Harrison; Christopher D Lucas. 2020. "Tissue-specific tolerance in fatal Covid-19." , no. : 1.
The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium. Graphical Abstract Highlights Proteome of airway secretions derived from mock- and hRSV-infected WD-PBEC cultures. A polarised secretome in uninfected WD-PBECs, skewed in hRSV-infected cultures. CXCL6, CXCL16, CECACAM1 and CSF3 induced only upon hRSV-infection. Detection of CXCL6, CXCL16 and CSF3 in NPAs from hRSV-positive children.
Olivier Touzelet; Lindsay Broadbent; Stuart D. Armstrong; Waleed Aljabr; Elaine Cloutman-Green; Ultan F. Power; Julian A. Hiscox. The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins. Molecular & Cellular Proteomics 2020, 19, 793 -807.
AMA StyleOlivier Touzelet, Lindsay Broadbent, Stuart D. Armstrong, Waleed Aljabr, Elaine Cloutman-Green, Ultan F. Power, Julian A. Hiscox. The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins. Molecular & Cellular Proteomics. 2020; 19 (5):793-807.
Chicago/Turabian StyleOlivier Touzelet; Lindsay Broadbent; Stuart D. Armstrong; Waleed Aljabr; Elaine Cloutman-Green; Ultan F. Power; Julian A. Hiscox. 2020. "The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins." Molecular & Cellular Proteomics 19, no. 5: 793-807.
COVID-19 is a complex disease phenotype where the underlying microbiome could influence morbidity and mortality. Amplicon and metagenomic MinION based sequencing was used to rapidly (within 8 hours) identify SARS-CoV-2 and assess the microbiome in nasopharyngeal swabs obtained from patients with COVID-19 by the ISARIC 4C consortium.
Shona C. Moore; Rebekah Penrice-Randal; Muhannad Alruwaili; Xiaofeng Dong; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Qin Zhao; Yani Sun; Catherine Hartley; En-Min Zhou; Tom Solomon; Michael B. J. Beadsworth; James Cruise; Debby Bogaert; Derrick W T Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard T. Vipond; Lisa F. P. Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; Malcolm G. Semple; Lance Turtle; Julian Alexander Hiscox. Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19. 2020, 1 .
AMA StyleShona C. Moore, Rebekah Penrice-Randal, Muhannad Alruwaili, Xiaofeng Dong, Steven T. Pullan, Daniel P. Carter, Kevin Bewley, Qin Zhao, Yani Sun, Catherine Hartley, En-Min Zhou, Tom Solomon, Michael B. J. Beadsworth, James Cruise, Debby Bogaert, Derrick W T Crook, David A. Matthews, Andrew D. Davidson, Zana Mahmood, Waleed Aljabr, Julian Druce, Richard T. Vipond, Lisa F. P. Ng, Laurent Renia, Peter J. M. Openshaw, J. Kenneth Baillie, Miles W. Carroll, Malcolm G. Semple, Lance Turtle, Julian Alexander Hiscox. Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19. . 2020; ():1.
Chicago/Turabian StyleShona C. Moore; Rebekah Penrice-Randal; Muhannad Alruwaili; Xiaofeng Dong; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Qin Zhao; Yani Sun; Catherine Hartley; En-Min Zhou; Tom Solomon; Michael B. J. Beadsworth; James Cruise; Debby Bogaert; Derrick W T Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard T. Vipond; Lisa F. P. Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; Malcolm G. Semple; Lance Turtle; Julian Alexander Hiscox. 2020. "Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19." , no. : 1.
Hand, foot and mouth disease (HFMD), caused by enterovirus A71 (EV-A71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV-A71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterised in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV-A71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV-A71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signalling. Depletion of TREM-1 in EV-A71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV-A71 infections in primary human cells, and the potential involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
Siti Naqiah Amrun; Jeslin J. L. Tan; Natasha Rickett; Jonathan A. Cox; Bernett Lee; Michael J. Griffiths; Tom Solomon; David Perera; Mong How Ooi; Julian A. Hiscox; Lisa F. P. Ng. TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection. Scientific Reports 2020, 10, 3810 -13.
AMA StyleSiti Naqiah Amrun, Jeslin J. L. Tan, Natasha Rickett, Jonathan A. Cox, Bernett Lee, Michael J. Griffiths, Tom Solomon, David Perera, Mong How Ooi, Julian A. Hiscox, Lisa F. P. Ng. TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection. Scientific Reports. 2020; 10 (1):3810-13.
Chicago/Turabian StyleSiti Naqiah Amrun; Jeslin J. L. Tan; Natasha Rickett; Jonathan A. Cox; Bernett Lee; Michael J. Griffiths; Tom Solomon; David Perera; Mong How Ooi; Julian A. Hiscox; Lisa F. P. Ng. 2020. "TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection." Scientific Reports 10, no. 1: 3810-13.
Controlling outbreaks will require detailed knowledge of their biology and behaviour Coronaviruses have been around for many years and were first discovered in the 1960s. They include viruses contributing to the common cold (HCoV-229E) and a variety of animal and avian coronaviruses, such as infectious bronchitis virus (IBV), which infects poultry. Coronaviruses typically cause respiratory or gastrointestinal illness, but strains of IBV have been shown to target the oviduct in chickens, and others can cause severe kidney disease. Animal and avian coronaviruses can have high mortality rates among infected animals and illustrate the difficulties in developing vaccines. Similar to influenza viruses, despite many decades of research there is no vaccine that protects against all strains of IBV coronavirus. This is due in part to the continuously shifting diversity in the virus spike glycoprotein, a major immunogenic target and hence a good vaccine candidate for animal and human infections. During the mid-1990s these viruses were described as the backwater of virology, since none caused serious disease in humans. However, this changed in 2002-03 with …
Lisa F P Ng; Julian A Hiscox. Coronaviruses in animals and humans. BMJ 2020, 368, m634 .
AMA StyleLisa F P Ng, Julian A Hiscox. Coronaviruses in animals and humans. BMJ. 2020; 368 ():m634.
Chicago/Turabian StyleLisa F P Ng; Julian A Hiscox. 2020. "Coronaviruses in animals and humans." BMJ 368, no. : m634.
Recent studies have shown that transcriptomic analysis of blood samples taken from patients with acute Ebola virus disease (EVD) during the 2013–2016 West African outbreak was suggestive that a severe inflammatory response took place in acutely ill patients. The significant knowledge gained from studying the Makona variant, a cause of the largest known EVD outbreak, may be applicable to other species of ebolavirus, and other variants of the Ebola virus (EBOV) species. To investigate the ability of Makona to initiate an inflammatory response in human macrophages and characterise the host response in a similar manner to previously characterised EBOV variants, the human monocytic cell line THP-1 was differentiated into macrophage-like cells and infected with Makona. RNA-Seq and quantitative proteomics were used to identify and quantify host mRNA and protein abundance during infection. Data from infection with Reston virus (RESTV) were used as comparators to investigate changes that may be specific to, or enhanced in, Makona infection in relation to a less pathogenic species of ebolavirus.. This study found demonstrable induction of the inflammatory response, and increase in the activation state of THP-1 macrophages infected with Makona. NFκB and inflammation-associated transcripts displayed significant changes in abundance, reflective of what was observed in human patients during the 2013–2016 EBOV outbreak in West Africa, and demonstrated that transcriptomic changes found in Makona-infected cells were similar to that observed in Reston virus infection and that have been described in previous studies of other variants of EBOV.
Andrew Bosworth; Stuart D. Dowall; Stuart Armstrong; Xuan Liu; Xiaofeng Dong; Christine B. Bruce; Lisa F. P. Ng; Miles W. Carroll; Roger Hewson; Julian A. Hiscox. Investigating the Cellular Transcriptomic Response Induced by the Makona Variant of Ebola Virus in Differentiated THP-1 Cells. Viruses 2019, 11, 1023 .
AMA StyleAndrew Bosworth, Stuart D. Dowall, Stuart Armstrong, Xuan Liu, Xiaofeng Dong, Christine B. Bruce, Lisa F. P. Ng, Miles W. Carroll, Roger Hewson, Julian A. Hiscox. Investigating the Cellular Transcriptomic Response Induced by the Makona Variant of Ebola Virus in Differentiated THP-1 Cells. Viruses. 2019; 11 (11):1023.
Chicago/Turabian StyleAndrew Bosworth; Stuart D. Dowall; Stuart Armstrong; Xuan Liu; Xiaofeng Dong; Christine B. Bruce; Lisa F. P. Ng; Miles W. Carroll; Roger Hewson; Julian A. Hiscox. 2019. "Investigating the Cellular Transcriptomic Response Induced by the Makona Variant of Ebola Virus in Differentiated THP-1 Cells." Viruses 11, no. 11: 1023.
Human respiratory syncytial virus (HRSV) is a major cause of pediatric infection and also causes disease in the elderly and those with underlying respiratory problems. There is no vaccine for HRSV and anti-viral therapeutics are not broadly applicable. To investigate the effect of HRSV biology in children, nasopharyngeal aspirates were taken from children with different viral loads and a combined high throughput RNAseq and label free quantitative proteomics approach was used to characterize the nucleic acid and proteins in these samples. HRSV proteins were identified in the nasopharyngeal aspirates from infected children, and their abundance correlated with viral load (Ct value), confirming HRSV infection. Analysis of the HRSV genome indicated that the children were infected with sub-group A virus and that minor variants in nucleotide frequency occurred in discrete clusters along the HRSV genome, and within a patient clustered distinctly within the glycoprotein gene. Data from the samples were binned into four groups; no-HRSV infection (control), high viral load (Ct < 20), medium viral load (Ct = 20-25), and low viral load (Ct > 25). Cellular proteins associated with the anti-viral response (e.g., ISG15) were identified in the nasopharyngeal aspirates and their abundance was correlated with viral load. These combined approaches have not been used before to study HRSV biology in vivo and can be readily applied to the study the variation of virus host interactions.
Waleed Aljabr; Stuart Armstrong; Natasha Y. Rickett; Georgios Pollakis; Olivier Touzelet; Elaine Cloutman-Green; David A. Matthews; Julian A. Hiscox. High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo. Viruses 2019, 11, 926 .
AMA StyleWaleed Aljabr, Stuart Armstrong, Natasha Y. Rickett, Georgios Pollakis, Olivier Touzelet, Elaine Cloutman-Green, David A. Matthews, Julian A. Hiscox. High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo. Viruses. 2019; 11 (10):926.
Chicago/Turabian StyleWaleed Aljabr; Stuart Armstrong; Natasha Y. Rickett; Georgios Pollakis; Olivier Touzelet; Elaine Cloutman-Green; David A. Matthews; Julian A. Hiscox. 2019. "High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo." Viruses 11, no. 10: 926.