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  1. Article ; Online: Cell Type Variability in the Incorporation of Lipids in the Dengue Virus Virion.

    Hitakarun, Atitaya / Williamson, Maia Kavanagh / Yimpring, Nathamon / Sornjai, Wannapa / Wikan, Nitwara / Arthur, Christopher J / Pompon, Julien / Davidson, Andrew D / Smith, Duncan R

    Viruses

    2022  Volume 14, Issue 11

    Abstract: A lipid bilayer produced from the host membrane makes up around 20% of the weight of the dengue virus (DENV) virion and is crucial for virus entry. Despite its significance, the virion's lipid composition is still poorly understood. In tandem with lipid ... ...

    Abstract A lipid bilayer produced from the host membrane makes up around 20% of the weight of the dengue virus (DENV) virion and is crucial for virus entry. Despite its significance, the virion's lipid composition is still poorly understood. In tandem with lipid profiles of the cells utilised to generate the virions, this work determined a partial lipid profile of DENV virions derived from two cell lines (C6/36 and LLC-MK
    MeSH term(s) Animals ; Dengue Virus/physiology ; Virion/metabolism ; Cell Line ; Culicidae ; Lipid Bilayers/metabolism ; Mammals
    Chemical Substances Lipid Bilayers
    Language English
    Publishing date 2022-11-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14112566
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription.

    Almuqrin, Abdulaziz / Davidson, Andrew D / Williamson, Maia Kavanagh / Lewis, Philip A / Heesom, Kate J / Morris, Susan / Gilbert, Sarah C / Matthews, David A

    Genome medicine

    2021  Volume 13, Issue 1, Page(s) 43

    Abstract: Background: ChAdOx1 nCoV-19 is a recombinant adenovirus vaccine against SARS-CoV-2 that has passed phase III clinical trials and is now in use across the globe. Although replication-defective in normal cells, 28 kbp of adenovirus genes is delivered to ... ...

    Abstract Background: ChAdOx1 nCoV-19 is a recombinant adenovirus vaccine against SARS-CoV-2 that has passed phase III clinical trials and is now in use across the globe. Although replication-defective in normal cells, 28 kbp of adenovirus genes is delivered to the cell nucleus alongside the SARS-CoV-2 S glycoprotein gene.
    Methods: We used direct RNA sequencing to analyse transcript expression from the ChAdOx1 nCoV-19 genome in human MRC-5 and A549 cell lines that are non-permissive for vector replication alongside the replication permissive cell line, HEK293. In addition, we used quantitative proteomics to study over time the proteome and phosphoproteome of A549 and MRC5 cells infected with the ChAdOx1 nCoV-19 vaccine.
    Results: The expected SARS-CoV-2 S coding transcript dominated in all cell lines. We also detected rare S transcripts with aberrant splice patterns or polyadenylation site usage. Adenovirus vector transcripts were almost absent in MRC-5 cells, but in A549 cells, there was a broader repertoire of adenoviral gene expression at very low levels. Proteomically, in addition to S glycoprotein, we detected multiple adenovirus proteins in A549 cells compared to just one in MRC5 cells.
    Conclusions: Overall, the ChAdOx1 nCoV-19 vaccine's transcriptomic and proteomic repertoire in cell culture is as expected. The combined transcriptomic and proteomics approaches provide a detailed insight into the behaviour of this important class of vaccine using state-of-the-art techniques and illustrate the potential of this technique to inform future viral vaccine vector design.
    MeSH term(s) COVID-19/immunology ; COVID-19/metabolism ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Vaccines/adverse effects ; COVID-19 Vaccines/genetics ; COVID-19 Vaccines/immunology ; Cell Line ; Cells, Cultured ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Polyadenylation ; Proteomics/methods ; RNA, Messenger ; RNA, Viral ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Transcription, Genetic
    Chemical Substances COVID-19 Vaccines ; RNA, Messenger ; RNA, Viral ; Spike Glycoprotein, Coronavirus
    Language English
    Publishing date 2021-03-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-021-00859-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2.

    Gupta, Kapil / Toelzer, Christine / Williamson, Maia Kavanagh / Shoemark, Deborah K / Oliveira, A Sofia F / Matthews, David A / Almuqrin, Abdulaziz / Staufer, Oskar / Yadav, Sathish K N / Borucu, Ufuk / Garzoni, Frederic / Fitzgerald, Daniel / Spatz, Joachim / Mulholland, Adrian J / Davidson, Andrew D / Schaffitzel, Christiane / Berger, Imre

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 222

    Abstract: As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single ... ...

    Abstract As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.
    MeSH term(s) Animals ; COVID-19/virology ; Cell Line ; Cryoelectron Microscopy ; Evolution, Molecular ; Furin/metabolism ; Humans ; Linoleic Acid/metabolism ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Protein Conformation ; SARS-CoV-2/chemistry ; SARS-CoV-2/genetics ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Viral Tropism ; Virus Internalization
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Linoleic Acid (9KJL21T0QJ) ; Furin (EC 3.4.21.75)
    Language English
    Publishing date 2022-01-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-27881-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein.

    Davidson, Andrew D / Williamson, Maia Kavanagh / Lewis, Sebastian / Shoemark, Deborah / Carroll, Miles W / Heesom, Kate J / Zambon, Maria / Ellis, Joanna / Lewis, Philip A / Hiscox, Julian A / Matthews, David A

    Genome medicine

    2020  Volume 12, Issue 1, Page(s) 68

    Abstract: Background: SARS-CoV-2 is a recently emerged respiratory pathogen that has significantly impacted global human health. We wanted to rapidly characterise the transcriptomic, proteomic and phosphoproteomic landscape of this novel coronavirus to provide a ... ...

    Abstract Background: SARS-CoV-2 is a recently emerged respiratory pathogen that has significantly impacted global human health. We wanted to rapidly characterise the transcriptomic, proteomic and phosphoproteomic landscape of this novel coronavirus to provide a fundamental description of the virus's genomic and proteomic potential.
    Methods: We used direct RNA sequencing to determine the transcriptome of SARS-CoV-2 grown in Vero E6 cells which is widely used to propagate the novel coronavirus. The viral transcriptome was analysed using a recently developed ORF-centric pipeline. Allied to this, we used tandem mass spectrometry to investigate the proteome and phosphoproteome of the same virally infected cells.
    Results: Our integrated analysis revealed that the viral transcripts (i.e. subgenomic mRNAs) generally fitted the expected transcription model for coronaviruses. Importantly, a 24 nt in-frame deletion was detected in over half of the subgenomic mRNAs encoding the spike (S) glycoprotein and was predicted to remove a proposed furin cleavage site from the S glycoprotein. Tandem mass spectrometry identified over 500 viral peptides and 44 phosphopeptides in virus-infected cells, covering almost all proteins predicted to be encoded by the SARS-CoV-2 genome, including peptides unique to the deleted variant of the S glycoprotein.
    Conclusions: Detection of an apparently viable deletion in the furin cleavage site of the S glycoprotein, a leading vaccine target, shows that this and other regions of SARS-CoV-2 proteins may readily mutate. The furin site directs cleavage of the S glycoprotein into functional subunits during virus entry or exit and likely contributes strongly to the pathogenesis and zoonosis of this virus. Our data emphasises that the viral genome sequence should be carefully monitored during the growth of viral stocks for research, animal challenge models and, potentially, in clinical samples. Such variations may result in different levels of virulence, morbidity and mortality.
    MeSH term(s) Animals ; Betacoronavirus/genetics ; Betacoronavirus/growth & development ; Betacoronavirus/metabolism ; Chlorocebus aethiops ; Gene Expression Profiling/methods ; Phosphorylation ; Proteomics/methods ; SARS-CoV-2 ; Sequence Analysis, RNA ; Sequence Deletion ; Serial Passage ; Spike Glycoprotein, Coronavirus/genetics ; Tandem Mass Spectrometry ; Vero Cells
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-07-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-020-00763-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Nanopore ReCappable sequencing maps SARS-CoV-2 5' capping sites and provides new insights into the structure of sgRNAs.

    Ugolini, Camilla / Mulroney, Logan / Leger, Adrien / Castelli, Matteo / Criscuolo, Elena / Williamson, Maia Kavanagh / Davidson, Andrew D / Almuqrin, Abdulaziz / Giambruno, Roberto / Jain, Miten / Frigè, Gianmaria / Olsen, Hugh / Tzertzinis, George / Schildkraut, Ira / Wulf, Madalee G / Corrêa, Ivan R / Ettwiller, Laurence / Clementi, Nicola / Clementi, Massimo /
    Mancini, Nicasio / Birney, Ewan / Akeson, Mark / Nicassio, Francesco / Matthews, David A / Leonardi, Tommaso

    Nucleic acids research

    2022  Volume 50, Issue 6, Page(s) 3475–3489

    Abstract: The SARS-CoV-2 virus has a complex transcriptome characterised by multiple, nested subgenomic RNAsused to express structural and accessory proteins. Long-read sequencing technologies such as nanopore direct RNA sequencing can recover full-length ... ...

    Abstract The SARS-CoV-2 virus has a complex transcriptome characterised by multiple, nested subgenomic RNAsused to express structural and accessory proteins. Long-read sequencing technologies such as nanopore direct RNA sequencing can recover full-length transcripts, greatly simplifying the assembly of structurally complex RNAs. However, these techniques do not detect the 5' cap, thus preventing reliable identification and quantification of full-length, coding transcript models. Here we used Nanopore ReCappable Sequencing (NRCeq), a new technique that can identify capped full-length RNAs, to assemble a complete annotation of SARS-CoV-2 sgRNAs and annotate the location of capping sites across the viral genome. We obtained robust estimates of sgRNA expression across cell lines and viral isolates and identified novel canonical and non-canonical sgRNAs, including one that uses a previously un-annotated leader-to-body junction site. The data generated in this work constitute a useful resource for the scientific community and provide important insights into the mechanisms that regulate the transcription of SARS-CoV-2 sgRNAs.
    MeSH term(s) COVID-19/genetics ; Genome, Viral/genetics ; Humans ; Nanopores ; RNA Caps ; RNA, Viral/genetics ; RNA, Viral/metabolism ; SARS-CoV-2/genetics
    Chemical Substances RNA Caps ; RNA, Viral
    Language English
    Publishing date 2022-02-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkac144
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The free fatty acid-binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron.

    Toelzer, Christine / Gupta, Kapil / Yadav, Sathish K N / Hodgson, Lorna / Williamson, Maia Kavanagh / Buzas, Dora / Borucu, Ufuk / Powers, Kyle / Stenner, Richard / Vasileiou, Kate / Garzoni, Frederic / Fitzgerald, Daniel / Payré, Christine / Gautam, Gunjan / Lambeau, Gérard / Davidson, Andrew D / Verkade, Paul / Frank, Martin / Berger, Imre /
    Schaffitzel, Christiane

    Science advances

    2022  Volume 8, Issue 47, Page(s) eadc9179

    Abstract: As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid ( ... ...

    Abstract As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold-causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation, while the open, infectious conformation is devoid of LA. Electron tomography of SARS-CoV-2-infected cells reveals that LA treatment inhibits viral replication, resulting in fewer deformed virions. Our results establish FFA binding as a hallmark of pathogenic β-CoV infection and replication, setting the stage for FFA-based antiviral strategies to overcome COVID-19.
    MeSH term(s) Humans ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Fatty Acids, Nonesterified ; COVID-19 ; SARS-CoV-2
    Chemical Substances spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Fatty Acids, Nonesterified
    Language English
    Publishing date 2022-11-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adc9179
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  7. Article ; Online: The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection.

    Goldswain, Hannah / Dong, Xiaofeng / Penrice-Randal, Rebekah / Alruwaili, Muhannad / Shawli, Ghada T / Prince, Tessa / Williamson, Maia Kavanagh / Raghwani, Jayna / Randle, Nadine / Jones, Benjamin / Donovan-Banfield, I'ah / Salguero, Francisco J / Tree, Julia A / Hall, Yper / Hartley, Catherine / Erdmann, Maximilian / Bazire, James / Jearanaiwitayakul, Tuksin / Semple, Malcolm G /
    Openshaw, Peter J M / Baillie, J Kenneth / Emmett, Stevan R / Digard, Paul / Matthews, David A / Turtle, Lance / Darby, Alistair C / Davidson, Andrew D / Carroll, Miles W / Hiscox, Julian A

    Genome biology

    2023  Volume 24, Issue 1, Page(s) 47

    Abstract: Background: The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated ...

    Abstract Background: The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure.
    Results: Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323.
    Conclusions: These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Pandemics ; Genetic Background ; Genome, Viral ; Mutation
    Language English
    Publishing date 2023-03-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-023-02881-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets.

    Peacock, Thomas P / Goldhill, Daniel H / Zhou, Jie / Baillon, Laury / Frise, Rebecca / Swann, Olivia C / Kugathasan, Ruthiran / Penn, Rebecca / Brown, Jonathan C / Sanchez-David, Raul Y / Braga, Luca / Williamson, Maia Kavanagh / Hassard, Jack A / Staller, Ecco / Hanley, Brian / Osborn, Michael / Giacca, Mauro / Davidson, Andrew D / Matthews, David A /
    Barclay, Wendy S

    Nature microbiology

    2021  Volume 6, Issue 7, Page(s) 899–909

    Abstract: SARS-CoV-2 entry requires sequential cleavage of the spike glycoprotein at the S1/S2 and the S2' cleavage sites to mediate membrane fusion. SARS-CoV-2 has a polybasic insertion (PRRAR) at the S1/S2 cleavage site that can be cleaved by furin. Using ... ...

    Abstract SARS-CoV-2 entry requires sequential cleavage of the spike glycoprotein at the S1/S2 and the S2' cleavage sites to mediate membrane fusion. SARS-CoV-2 has a polybasic insertion (PRRAR) at the S1/S2 cleavage site that can be cleaved by furin. Using lentiviral pseudotypes and a cell-culture-adapted SARS-CoV-2 virus with an S1/S2 deletion, we show that the polybasic insertion endows SARS-CoV-2 with a selective advantage in lung cells and primary human airway epithelial cells, but impairs replication in Vero E6, a cell line used for passaging SARS-CoV-2. Using engineered spike variants and live virus competition assays and by measuring growth kinetics, we find that the selective advantage in lung and primary human airway epithelial cells depends on the expression of the cell surface protease TMPRSS2, which enables endosome-independent virus entry by a route that avoids antiviral IFITM proteins. SARS-CoV-2 virus lacking the S1/S2 furin cleavage site was shed to lower titres from infected ferrets and was not transmitted to cohoused sentinel animals, unlike wild-type virus. Analysis of 100,000 SARS-CoV-2 sequences derived from patients and 24 human postmortem tissues showed low frequencies of naturally occurring mutants that harbour deletions at the polybasic site. Taken together, our findings reveal that the furin cleavage site is an important determinant of SARS-CoV-2 transmission.
    MeSH term(s) Animals ; COVID-19/transmission ; COVID-19/virology ; Cathepsins/metabolism ; Chlorocebus aethiops ; Endosomes/metabolism ; Epithelial Cells ; Ferrets ; Furin/metabolism ; Humans ; Immune Evasion ; Membrane Proteins/metabolism ; RNA-Binding Proteins/metabolism ; Respiratory System/cytology ; Respiratory System/virology ; SARS-CoV-2/physiology ; Serine Endopeptidases/metabolism ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Vero Cells ; Viral Genome Packaging ; Virus Internalization ; Virus Replication ; Virus Shedding
    Chemical Substances IFITM3 protein, human ; Membrane Proteins ; RNA-Binding Proteins ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Cathepsins (EC 3.4.-) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; Furin (EC 3.4.21.75)
    Language English
    Publishing date 2021-04-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-021-00908-w
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  9. Article ; Online: Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2.

    Goenka, Anu / Halliday, Alice / Gregorova, Michaela / Milodowski, Emily / Thomas, Amy / Williamson, Maia Kavanagh / Baum, Holly / Oliver, Elizabeth / Long, Anna E / Knezevic, Lea / Williams, Alistair J K / Lampasona, Vito / Piemonti, Lorenzo / Gupta, Kapil / Di Bartolo, Natalie / Berger, Imre / Toye, Ashley M / Vipond, Barry / Muir, Peter /
    Bernatoniene, Jolanta / Bailey, Mick / Gillespie, Kathleen M / Davidson, Andrew D / Wooldridge, Linda / Rivino, Laura / Finn, Adam

    Cell reports. Medicine

    2021  Volume 2, Issue 7, Page(s) 100327

    Abstract: Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in 4 infants under 3 months old with confirmed ... ...

    Abstract Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in 4 infants under 3 months old with confirmed COVID-19 who presented with mild febrile illness, alongside their parents, and adult controls recovered from confirmed COVID-19. Although not statistically significant, compared to seropositive adults, infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein, with a corresponding functional ability to block SARS-CoV-2 cellular entry. Infants also exhibit robust saliva anti-spike IgG and IgA responses. Spike-specific IFN-γ production by infant peripheral blood mononuclear cells appears restrained, but the frequency of spike-specific IFN-γ- and/or TNF-α-producing T cells is comparable between infants and adults. On principal-component analysis, infant immune responses appear distinct from their parents. Robust functional antibody responses alongside restrained IFN-γ production may help protect infants from severe COVID-19.
    MeSH term(s) Adult ; Antibody Formation ; COVID-19/immunology ; Female ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Infant ; Infant, Newborn ; Interferon-gamma/immunology ; Interferon-gamma/metabolism ; Leukocytes, Mononuclear/metabolism ; Male ; Spike Glycoprotein, Coronavirus/immunology ; Young Adult
    Chemical Substances Immunoglobulin A ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2021-06-09
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2021.100327
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  10. Article ; Online: Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein

    Davidson, Andrew D. / Williamson, Maia Kavanagh / Lewis, Sebastian / Shoemark, Deborah / Carroll, Miles W. / Heesom, Kate J. / Zambon, Maria / Ellis, Joanna / Lewis, Philip A. / Hiscox, Julian A. / Matthews, David A.

    Genome Medicine

    2020  Volume 12, Issue 1

    Keywords Genetics(clinical) ; Molecular Medicine ; Genetics ; Molecular Biology ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2484394-5
    ISSN 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-020-00763-0
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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