دورية أكاديمية
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.
العنوان: | Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. |
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المؤلفون: | Swadling L; Division of Infection and Immunity, University College London, London, UK. l.swadling@ucl.ac.uk., Diniz MO; Division of Infection and Immunity, University College London, London, UK., Schmidt NM; Division of Infection and Immunity, University College London, London, UK., Amin OE; Division of Infection and Immunity, University College London, London, UK., Chandran A; Division of Infection and Immunity, University College London, London, UK., Shaw E; Division of Infection and Immunity, University College London, London, UK., Pade C; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Gibbons JM; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Le Bert N; Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore., Tan AT; Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore., Jeffery-Smith A; Division of Infection and Immunity, University College London, London, UK.; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Tan CCS; UCL Genetics Institute, University College London, London, UK., Tham CYL; Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore., Kucykowicz S; Division of Infection and Immunity, University College London, London, UK., Aidoo-Micah G; Division of Infection and Immunity, University College London, London, UK., Rosenheim J; Division of Infection and Immunity, University College London, London, UK., Davies J; Division of Infection and Immunity, University College London, London, UK., Johnson M; Great Ormond Street Institute of Child Health NIHR Biomedical Research Centre, University College London, London, UK., Jensen MP; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.; Department of Cellular Pathology, Northwest London Pathology, Imperial College London NHS Trust, London, UK., Joy G; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.; Institute of Cardiovascular Science, University College London, London, UK., McCoy LE; Division of Infection and Immunity, University College London, London, UK., Valdes AM; Academic Rheumatology, Clinical Sciences, Nottingham City Hospital, Nottingham, UK.; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK., Chain BM; Division of Infection and Immunity, University College London, London, UK., Goldblatt D; Great Ormond Street Institute of Child Health NIHR Biomedical Research Centre, University College London, London, UK., Altmann DM; Department of Immunology and Inflammation, Imperial College London, London, UK., Boyton RJ; Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.; Lung Division, Royal Brompton & Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK., Manisty C; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.; Institute of Cardiovascular Science, University College London, London, UK., Treibel TA; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.; Institute of Cardiovascular Science, University College London, London, UK., Moon JC; Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.; Institute of Cardiovascular Science, University College London, London, UK., van Dorp L; UCL Genetics Institute, University College London, London, UK., Balloux F; UCL Genetics Institute, University College London, London, UK., McKnight Á; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Noursadeghi M; Division of Infection and Immunity, University College London, London, UK., Bertoletti A; Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore.; Singapore Immunology Network, A*STAR, Singapore, Singapore., Maini MK; Division of Infection and Immunity, University College London, London, UK. m.maini@ucl.ac.uk. |
مؤلفون مشاركون: | COVIDsortium Investigators |
المصدر: | Nature [Nature] 2022 Jan; Vol. 601 (7891), pp. 110-117. Date of Electronic Publication: 2021 Nov 10. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
مواضيع طبية MeSH: | Asymptomatic Infections* , Seroconversion*, COVID-19/*immunology , COVID-19/*virology , DNA-Directed RNA Polymerases/*immunology , Memory T Cells/*immunology , SARS-CoV-2/*immunology, Cell Proliferation ; Cohort Studies ; DNA-Directed RNA Polymerases/metabolism ; Evolution, Molecular ; Female ; Health Personnel ; Humans ; Male ; Membrane Proteins/immunology ; Memory T Cells/cytology ; Multienzyme Complexes/immunology ; SARS-CoV-2/enzymology ; SARS-CoV-2/growth & development ; Transcription, Genetic/immunology |
مستخلص: | Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections 1-3 . Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4-11 ), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication-transcription complex (RTC) 12,13 , in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. 14 ), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae. (© 2021. The Author(s).) |
التعليقات: | Comment in: Nature. 2021 Nov;599(7886):543. (PMID: 34773110) Comment in: Nat Rev Immunol. 2022 Jan;22(1):5. (PMID: 34873280) Comment in: Ann Rheum Dis. 2022 Jun;81(6):757-759. (PMID: 35393270) |
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معلومات مُعتمدة: | MR/V027883/1 United Kingdom MRC_ Medical Research Council; MC_PC_20031 United Kingdom MRC_ Medical Research Council; MR/S019553/1 United Kingdom MRC_ Medical Research Council; MR/R02622X/1 United Kingdom MRC_ Medical Research Council; MR/W020610/1 United Kingdom MRC_ Medical Research Council; 26603 United Kingdom CRUK_ Cancer Research UK; MRF_MRF-044-0001-RG-SWADL United Kingdom MRF MRF; MC_PC_20060 United Kingdom MRC_ Medical Research Council; FS/CRTF/21/24128 United Kingdom BHF_ British Heart Foundation; 214191/Z/18/Z United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; MR/V036939/1 United Kingdom MRC_ Medical Research Council; MR/R008698/1 United Kingdom MRC_ Medical Research Council; FS/18/21/33447 United Kingdom BHF_ British Heart Foundation; 207511/Z/17/Z United Kingdom WT_ Wellcome Trust |
فهرسة مساهمة: | Investigator: H Abbass; A Abiodun; M Alfarih; Z Alldis; M Andiapen; J Artico; JB Augusto; GL Baca; SNL Bailey; AN Bhuva; A Boulter; R Bowles; RJ Boyton; OV Bracken; B O'Brien; T Brooks; N Bullock; DK Butler; G Captur; N Champion; C Chan; D Collier; JC de Sousa; X Couto-Parada; T Cutino-Mogue; RH Davies; B Douglas; C Di Genova; K Dieobi-Anene; A Ellis; K Feehan; M Finlay; M Fontana; N Forooghi; C Gaier; D Gilroy; M Hamblin; G Harker; J Hewson; LM Hickling; AD Hingorani; L Howes; A Hughes; G Hughes; R Hughes; I Itua; V Jardim; WJ Lee; MP Jensen; J Jones; M Jones; G Joy; V Kapil; H Kurdi; J Lambourne; KM Lin; S Louth; V Mandadapu; Á McKnight; K Menacho; C Mfuko; O Mitchelmore; C Moon; D Munoz-Sandoval; SM Murray; M Noursadeghi; A Otter; S Palma; R Parker; K Patel; B Pawarova; SE Petersen; B Piniera; FP Pieper; D Pope; M Prossora; L Rannigan; A Rapala; CJ Reynolds; A Richards; M Robathan; G Sambile; A Semper; A Seraphim; M Simion; A Smit; M Sugimoto; S Taylor; N Temperton; S Thomas; GD Thornton; A Tucker; J Veerapen; M Vijayakumar; S Welch; T Wodehouse; L Wynne; D Zahedi |
المشرفين على المادة: | 0 (IFI27 protein, human) 0 (Membrane Proteins) 0 (Multienzyme Complexes) EC 2.7.7.6 (DNA-Directed RNA Polymerases) |
تواريخ الأحداث: | Date Created: 20211110 Date Completed: 20220111 Latest Revision: 20240323 |
رمز التحديث: | 20240323 |
مُعرف محوري في PubMed: | PMC8732273 |
DOI: | 10.1038/s41586-021-04186-8 |
PMID: | 34758478 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-4687 |
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DOI: | 10.1038/s41586-021-04186-8 |