Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion
Abstract 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 define...
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15668-8 |
| _version_ | 1797841079702126592 |
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| author | Nicholas S. Giroux Shengli Ding Micah T. McClain Thomas W. Burke Elizabeth Petzold Hong A. Chung Grecia O. Rivera Ergang Wang Rui Xi Shree Bose Tomer Rotstein Bradly P. Nicholson Tianyi Chen Ricardo Henao Gregory D. Sempowski Thomas N. Denny Maria Iglesias De Ussel Lisa L. Satterwhite Emily R. Ko Geoffrey S. Ginsburg Bryan D. Kraft Ephraim L. Tsalik Xiling Shen Christopher W. Woods |
| author_facet | Nicholas S. Giroux Shengli Ding Micah T. McClain Thomas W. Burke Elizabeth Petzold Hong A. Chung Grecia O. Rivera Ergang Wang Rui Xi Shree Bose Tomer Rotstein Bradly P. Nicholson Tianyi Chen Ricardo Henao Gregory D. Sempowski Thomas N. Denny Maria Iglesias De Ussel Lisa L. Satterwhite Emily R. Ko Geoffrey S. Ginsburg Bryan D. Kraft Ephraim L. Tsalik Xiling Shen Christopher W. Woods |
| author_sort | Nicholas S. Giroux |
| collection | DOAJ |
| description | Abstract 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 associated with mild or moderate symptoms were already robust and included 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 was marked by upregulation of classical antiviral pathways, including those regulating IRF1 and IRF7, whereas in moderate disease, these classical antiviral signals diminished, 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. |
| first_indexed | 2024-04-09T16:25:14Z |
| format | Article |
| id | doaj.art-734bc7f938d44704b53ab81adb346335 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T16:25:14Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-734bc7f938d44704b53ab81adb3463352023-04-23T11:13:13ZengNature PortfolioScientific Reports2045-23222022-07-0112111310.1038/s41598-022-15668-8Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversionNicholas S. Giroux0Shengli Ding1Micah T. McClain2Thomas W. Burke3Elizabeth Petzold4Hong A. Chung5Grecia O. Rivera6Ergang Wang7Rui Xi8Shree Bose9Tomer Rotstein10Bradly P. Nicholson11Tianyi Chen12Ricardo Henao13Gregory D. Sempowski14Thomas N. Denny15Maria Iglesias De Ussel16Lisa L. Satterwhite17Emily R. Ko18Geoffrey S. Ginsburg19Bryan D. Kraft20Ephraim L. Tsalik21Xiling Shen22Christopher W. Woods23Department of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Pharmacology and Cancer Biology, School of Medicine, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityInstitute for Medical ResearchDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineDuke Human Vaccine Institute and Department of Medicine, School of Medicine, Duke UniversityDuke Human Vaccine Institute and Department of Medicine, School of Medicine, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineDepartment of Civil and Environmental Engineering, Pratt School of Engineering, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University School of MedicineAbstract 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 associated with mild or moderate symptoms were already robust and included 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 was marked by upregulation of classical antiviral pathways, including those regulating IRF1 and IRF7, whereas in moderate disease, these classical antiviral signals diminished, 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.https://doi.org/10.1038/s41598-022-15668-8 |
| spellingShingle | Nicholas S. Giroux Shengli Ding Micah T. McClain Thomas W. Burke Elizabeth Petzold Hong A. Chung Grecia O. Rivera Ergang Wang Rui Xi Shree Bose Tomer Rotstein Bradly P. Nicholson Tianyi Chen Ricardo Henao Gregory D. Sempowski Thomas N. Denny Maria Iglesias De Ussel Lisa L. Satterwhite Emily R. Ko Geoffrey S. Ginsburg Bryan D. Kraft Ephraim L. Tsalik Xiling Shen Christopher W. Woods Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion Scientific Reports |
| title | Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion |
| title_full | Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion |
| title_fullStr | Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion |
| title_full_unstemmed | Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion |
| title_short | Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion |
| title_sort | differential chromatin accessibility in peripheral blood mononuclear cells underlies covid 19 disease severity prior to seroconversion |
| url | https://doi.org/10.1038/s41598-022-15668-8 |
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