Journal Article

DZNE-2024-00160

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons.

Passos, V. ; Henkel, L. M. ; Wang, J. ; Zapatero-Belinchón, F. J. ; Möller, R. ; Sun, G. ; Waltl, I. ; Schneider, T. ; Wachs, A. ; Ritter, B. ; Kropp, K. A. ; Zhu, S. ; Deleidi, M.DZNE* ; Kalinke, U. ; Schulz, T. F. ; Höglinger, G.Extern* ; Gerold, G. ; Wegner, F. ; Viejo-Borbolla, A.

2024
Wiley Bognor Regis [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1002/jmv.29455

Abstract: 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.

Keyword(s): Humans (MeSH) ; COVID-19 (MeSH) ; Induced Pluripotent Stem Cells (MeSH) ; SARS-CoV-2 (MeSH) ; Immunity, Innate (MeSH) ; Neurons (MeSH) ; JAK/STAT ; SARM1 ; SARS-CoV-2 ; iPSC-derived peripheral neurons ; interferon ; neuronal damage

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Contributing Institute(s):

1. Mitochondria and Inflammation in Neurodegenerative Diseases (AG Deleidi)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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