Identification of a Novel Susceptibility Marker for SARS-CoV-2 Infection in Human Subjects and Risk Mitigation with a Clinically Approved JAK Inhibitor in Human/Mouse Cells
Coronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020; www.who.int)1. While fatality rates are higher among the elderly and those with underlying comorbidities2, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.3-7 We report that the autoimmune PTPN2 risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 09. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Spalinger, Marianne R [VerfasserIn] |
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| Links: |
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| Themen: |
Autoimmune disease |
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| Anmerkungen: |
Date Revised 10.11.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.12.09.416586 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318959143 |
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| 245 | 1 | 0 | |a Identification of a Novel Susceptibility Marker for SARS-CoV-2 Infection in Human Subjects and Risk Mitigation with a Clinically Approved JAK Inhibitor in Human/Mouse Cells |
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| 500 | |a Date Revised 10.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Coronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020; www.who.int)1. While fatality rates are higher among the elderly and those with underlying comorbidities2, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.3-7 We report that the autoimmune PTPN2 risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk | ||
| 650 | 4 | |a Preprint | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Coronavirus | |
| 650 | 4 | |a Inflammatory Bowel Disease | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Tofacitinib | |
| 650 | 4 | |a autoimmune disease | |
| 650 | 4 | |a genetic susceptibility | |
| 700 | 1 | |a Hai, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiang |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, Alina N |e verfasserin |4 aut | |
| 700 | 1 | |a Nordgren, Tara M |e verfasserin |4 aut | |
| 700 | 1 | |a Tremblay, Michel L |e verfasserin |4 aut | |
| 700 | 1 | |a Eckmann, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Hanson, Elaine |e verfasserin |4 aut | |
| 700 | 1 | |a Scharl, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Boland, Brigid S |e verfasserin |4 aut | |
| 700 | 1 | |a McCole, Declan F |e verfasserin |4 aut | |
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