TY  - JOUR
AU  - Passos, Vania
AU  - Henkel, Lisa M
AU  - Wang, Jiayi
AU  - Zapatero-Belinchón, Francisco J
AU  - Möller, Rebecca
AU  - Sun, Guorong
AU  - Waltl, Inken
AU  - Schneider, Talia
AU  - Wachs, Amelie
AU  - Ritter, Birgit
AU  - Kropp, Kai A
AU  - Zhu, Shuyong
AU  - Deleidi, Michela
AU  - Kalinke, Ulrich
AU  - Schulz, Thomas F
AU  - Höglinger, Günter
AU  - Gerold, Gisa
AU  - Wegner, Florian
AU  - Viejo-Borbolla, Abel
TI  - Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons.
JO  - Journal of medical virology
VL  - 96
IS  - 2
SN  - 0146-6615
CY  - Bognor Regis [u.a.]
PB  - Wiley
M1  - DZNE-2024-00160
SP  - e29455
PY  - 2024
AB  - 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.
KW  - Humans
KW  - COVID-19
KW  - Induced Pluripotent Stem Cells
KW  - SARS-CoV-2
KW  - Immunity, Innate
KW  - Neurons
KW  - JAK/STAT (Other)
KW  - SARM1 (Other)
KW  - SARS-CoV-2 (Other)
KW  - iPSC-derived peripheral neurons (Other)
KW  - interferon (Other)
KW  - neuronal damage (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38323709
DO  - DOI:10.1002/jmv.29455
UR  - https://pub.dzne.de/record/267514
ER  -