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) |
| References: | Nature. 2020 Aug;584(7821):457-462. (PMID: 32668444) J Infect Dis. 2021 Jul 2;224(1):70-80. (PMID: 33822097) Nat Med. 2021 Jan;27(1):78-85. (PMID: 33184509) Science. 2020 Oct 2;370(6512):89-94. (PMID: 32753554) Science. 2021 May 14;372(6543):738-741. (PMID: 33846272) EBioMedicine. 2021 Mar;65:103259. (PMID: 33662833) Kidney Int Rep. 2021 Jul;6(7):1799-1809. (PMID: 33942026) Science. 2021 Jun 18;372(6548):1336-1341. (PMID: 34006597) Sci Immunol. 2021 Jul 1;6(61):. (PMID: 34210785) Immunology. 2022 May;166(1):78-103. (PMID: 35143694) Nat Commun. 2021 Mar 19;12(1):1724. (PMID: 33741972) Science. 2021 Oct 08;374(6564):eabh1823. (PMID: 34465633) Cytometry A. 2011 Feb;79(2):167-74. (PMID: 21265010) Science. 2020 Dec 11;370(6522):1339-1343. (PMID: 33159009) Nat Immunol. 2021 Jul;22(7):820-828. (PMID: 33976430) J Infect Dis. 2013 Sep;208(6):1020-5. (PMID: 23801608) J Clin Invest. 2021 Jan 4;131(1):. (PMID: 32997649) Proc Natl Acad Sci U S A. 1973 Dec;70(12):3321-3. (PMID: 4519626) Immunity. 2020 Nov 17;53(5):1095-1107.e3. (PMID: 33128877) Microb Genom. 2019 Jan;5(1):. (PMID: 30663960) Cell. 2020 Oct 1;183(1):158-168.e14. (PMID: 32979941) Leukemia. 2021 Jan;35(1):289-292. (PMID: 33299142) J Clin Virol. 2020 Sep;130:104572. (PMID: 32769024) Cell. 2020 Jun 25;181(7):1489-1501.e15. (PMID: 32473127) Med. 2021 Jun 11;2(6):682-688.e4. (PMID: 33851143) J Allergy Clin Immunol. 2021 Feb;147(2):545-557.e9. (PMID: 33221383) Nat Immunol. 2021 Jan;22(1):74-85. (PMID: 32999467) J Clin Invest. 2022 Jan 18;132(2):. (PMID: 34843448) Infect Genet Evol. 2021 Nov;95:105075. (PMID: 34509646) Nat Med. 1995 Jan;1(1):59-64. (PMID: 7584954) Nature. 2021 Sep;597(7875):268-273. (PMID: 34320609) Science. 2021 Apr 30;:. (PMID: 33931567) Gastroenterology. 2013 Nov;145(5):1026-34. (PMID: 23916846) J Exp Med. 2016 Jun 27;213(7):1331-52. (PMID: 27242166) Cell Rep. 2021 Feb 9;34(6):108728. (PMID: 33516277) Immunity. 2016 Jun 21;44(6):1379-91. (PMID: 27287409) Nat Commun. 2021 Apr 6;12(1):2055. (PMID: 33824342) Emerg Infect Dis. 2021 Jan;27(1):. (PMID: 33261718) Euro Surveill. 2017 Mar 30;22(13):. (PMID: 28382917) Lancet. 2020 May 23;395(10237):1608-1610. (PMID: 32401714) Wellcome Open Res. 2020 Jul 28;5:179. (PMID: 33537459) AIDS. 1994 Oct;8(10):1391-5. (PMID: 7818809) Nature. 2020 Nov;587(7833):270-274. (PMID: 32726801) Sci Transl Med. 2021 May 5;13(592):. (PMID: 33952677) Nat Rev Microbiol. 2009 Jun;7(6):439-50. (PMID: 19430490) Sci Immunol. 2020 Dec 23;5(54):. (PMID: 33361161) J Viral Hepat. 2010 Sep;17(9):631-9. (PMID: 19889141) Cell. 2021 Apr 1;184(7):1858-1864.e10. (PMID: 33631096) NPJ Vaccines. 2020 Oct 12;5:94. (PMID: 33083029) J Infect Dis. 2003 Apr 1;187(7):1053-63. (PMID: 12660919) Glob Chall. 2017 Jan 10;1(1):33-46. (PMID: 31565258) Cell Host Microbe. 2021 Jul 14;29(7):1076-1092. (PMID: 34237248) Lancet Microbe. 2021 Oct;2(10):e508-e517. (PMID: 34250515) |
| 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 |
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Full Text Finder | تدمد: | 1476-4687 |
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| DOI: | 10.1038/s41586-021-04186-8 |