%0 Journal Article
%A Passos, Vania
%A Henkel, Lisa M
%A Wang, Jiayi
%A Zapatero-Belinchón, Francisco J
%A Möller, Rebecca
%A Sun, Guorong
%A Waltl, Inken
%A Schneider, Talia
%A Wachs, Amelie
%A Ritter, Birgit
%A Kropp, Kai A
%A Zhu, Shuyong
%A Deleidi, Michela
%A Kalinke, Ulrich
%A Schulz, Thomas F
%A Höglinger, Günter
%A Gerold, Gisa
%A Wegner, Florian
%A Viejo-Borbolla, Abel
%T Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons.
%J Journal of medical virology
%V 96
%N 2
%@ 0146-6615
%C Bognor Regis [u.a.]
%I Wiley
%M DZNE-2024-00160
%P e29455
%D 2024
%X 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.
%K Humans
%K COVID-19
%K Induced Pluripotent Stem Cells
%K SARS-CoV-2
%K Immunity, Innate
%K Neurons
%K JAK/STAT (Other)
%K SARM1 (Other)
%K SARS-CoV-2 (Other)
%K iPSC-derived peripheral neurons (Other)
%K interferon (Other)
%K neuronal damage (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38323709
%R 10.1002/jmv.29455
%U https://pub.dzne.de/record/267514