Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.
| العنوان: | Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion. |
|---|---|
| المؤلفون: | Giroux NS; Duke University., Ding S; Duke University., McClain MT; Duke University School of Medicine., Burke TW; Duke University School of Medicine., Petzold E; Duke University School of Medicine., Chung HA; Duke University., Rivera GO; Duke University., Wang E; Duke University., Xi R; Duke University., Bose S; Duke University., Rotstein T; Duke University., Nicholson BP; Durham Veterans Affairs Health Care System., Chen T; Duke University., Henao R; Duke University School of Medicine., Sempowski GD; Duke University., Denny TN; Duke University., De Ussel MI; Duke University School of Medicine., Satterwhite LL; Duke University., Ko ER; Duke University School of Medicine., Ginsburg GS; Duke University School of Medicine., Kraft BD; Duke University School of Medicine., Tsalik EL; Duke University School of Medicine., Shen X; Duke University., Woods C; Duke University School of Medicine. |
| المصدر: | Research square [Res Sq] 2022 Apr 07. Date of Electronic Publication: 2022 Apr 07. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
| مستخلص: | SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associate with mild or moderate symptoms are already robust and include severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity is marked by upregulation classical antiviral pathways including those regulating IRF1 and IRF7, whereas in moderate disease these classical antiviral signals diminish suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19. |
| التعليقات: | Update in: Sci Rep. 2022 Jul 9;12(1):11714. doi: 10.1038/s41598-022-15668-8. (PMID: 35810186) |
| References: | Nat Genet. 2021 Mar;53(3):403-411. (PMID: 33633365) Front Immunol. 2020 Sep 30;11:582010. (PMID: 33117392) J Immunol. 2015 Jun 15;194(12):6011-23. (PMID: 25934862) Cell. 2020 Nov 12;183(4):1103-1116.e20. (PMID: 33098772) Nat Cell Biol. 2021 Jun;23(6):620-630. (PMID: 34108657) Sci Rep. 2020 Oct 7;10(1):16726. (PMID: 33028914) Mucosal Immunol. 2016 Sep;9(5):1250-62. (PMID: 26838049) Cell Host Microbe. 2020 Jun 10;27(6):870-878. (PMID: 32464097) Genome Biol. 2014 Feb 03;15(2):R29. (PMID: 24485249) Nat Rev Immunol. 2020 Oct;20(10):633-643. (PMID: 32782358) EBioMedicine. 2020 Sep;59:102948. (PMID: 32810827) Cell. 2020 May 28;181(5):1036-1045.e9. (PMID: 32416070) Cell. 2022 Mar 3;185(5):916-938.e58. (PMID: 35216673) N Engl J Med. 2020 Sep 10;383(11):1085-1087. (PMID: 32706954) Nat Med. 2020 Oct;26(10):1636-1643. (PMID: 32839624) Clin Infect Dis. 2020 Nov 19;71(16):2027-2034. (PMID: 32221519) Commun Biol. 2020 Nov 13;3(1):678. (PMID: 33188283) Nat Methods. 2019 May;16(5):397-400. (PMID: 30962623) Blood. 2009 Feb 12;113(7):1399-407. (PMID: 18757776) PLoS One. 2019 Oct 18;14(10):e0223980. (PMID: 31626638) Nat Med. 2020 Jun;26(6):845-848. (PMID: 32350462) Nucleic Acids Res. 2016 Mar 18;44(5):e45. (PMID: 26578583) Mediators Inflamm. 2017;2017:1434872. (PMID: 28757683) Nat Methods. 2017 Nov;14(11):1083-1086. (PMID: 28991892) Commun Med (Lond). 2021;1(1):42. (PMID: 35072167) J Exp Med. 2021 Aug 2;218(8):. (PMID: 34128959) Curr Protoc Mol Biol. 2015 Jan 05;109:21.29.1-21.29.9. (PMID: 25559105) J Leukoc Biol. 2021 Jul;110(1):21-26. (PMID: 33464637) Nat Rev Immunol. 2006 Jan;6(1):33-43. (PMID: 16341139) Front Immunol. 2021 Feb 24;12:625881. (PMID: 33717140) Cell Host Microbe. 2020 Jun 10;27(6):883-890.e2. (PMID: 32407669) Cell. 2019 Jun 13;177(7):1888-1902.e21. (PMID: 31178118) Cell. 2020 Sep 17;182(6):1419-1440.e23. (PMID: 32810438) Front Cardiovasc Med. 2018 Feb 05;5:6. (PMID: 29459900) |
| معلومات مُعتمدة: | 75N93019C00015 United States AI NIAID NIH HHS; K08 HL130557 United States HL NHLBI NIH HHS; R35 GM122465 United States GM NIGMS NIH HHS; UC6 AI058607 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20220412 Latest Revision: 20240615 |
| رمز التحديث: | 20240615 |
| مُعرف محوري في PubMed: | PMC8996625 |
| DOI: | 10.21203/rs.3.rs-1479864/v1 |
| PMID: | 35411343 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.21203/rs.3.rs-1479864/v1 |
|---|