Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons
© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC..
Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
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| Enthalten in: |
Journal of medical virology - 96(2024), 2 vom: 07. Feb., Seite e29455 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Passos, Vania [VerfasserIn] |
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| Links: |
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| Themen: |
IPSC-derived peripheral neurons |
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| Anmerkungen: |
Date Completed 08.02.2024 Date Revised 08.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.29455 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368129039 |
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| 520 | |a Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies | ||
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| 700 | 1 | |a Henkel, Lisa M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jiayi |e verfasserin |4 aut | |
| 700 | 1 | |a Zapatero-Belinchón, Francisco J |e verfasserin |4 aut | |
| 700 | 1 | |a Möller, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Guorong |e verfasserin |4 aut | |
| 700 | 1 | |a Waltl, Inken |e verfasserin |4 aut | |
| 700 | 1 | |a Schneider, Talia |e verfasserin |4 aut | |
| 700 | 1 | |a Wachs, Amelie |e verfasserin |4 aut | |
| 700 | 1 | |a Ritter, Birgit |e verfasserin |4 aut | |
| 700 | 1 | |a Kropp, Kai A |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Shuyong |e verfasserin |4 aut | |
| 700 | 1 | |a Deleidi, Michela |e verfasserin |4 aut | |
| 700 | 1 | |a Kalinke, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Schulz, Thomas F |e verfasserin |4 aut | |
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| 700 | 1 | |a Wegner, Florian |e verfasserin |4 aut | |
| 700 | 1 | |a Viejo-Borbolla, Abel |e verfasserin |4 aut | |
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