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Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons

Passos, Vania (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
Henkel, Lisa M. (författare)
Department of Neurology, Hannover Medical School, Hannover, Germany
Wang, Jiayi (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
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Zapatero-Belinchón, Francisco J. (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi,University of Veterinary Medicine Hannover, Foundation, Hannover, Germany; Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Hannover, Germany
Möller, Rebecca (författare)
University of Veterinary Medicine Hannover, Foundation, Hannover, Germany
Sun, Guorong (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
Waltl, Inken (författare)
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany
Schneider, Talia (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
Wachs, Amelie (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
Ritter, Birgit (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
Kropp, Kai A. (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
Zhu, Shuyong (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany
Deleidi, Michela (författare)
Center of Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Kalinke, Ulrich (författare)
Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Hannover, Germany; Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany
Schulz, Thomas F. (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany; Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Hannover, Germany
Höglinger, Günter (författare)
Department of Neurology, Hannover Medical School, Hannover, Germany; Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Hannover, Germany
Gerold, Gisa, 1979- (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),University of Veterinary Medicine Hannover, Foundation, Hannover, Germany; Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Hannover, Germany
Wegner, Florian (författare)
Department of Neurology, Hannover Medical School, Hannover, Germany
Viejo-Borbolla, Abel (författare)
Hannover Medical School, Institute of Virology, Hannover, Germany; Cluster of Excellence-Resolving Infection Susceptibility (RESIST), Hannover Medical School, Hannover, Germany
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 (creator_code:org_t)
John Wiley & Sons, 2024
2024
Engelska.
Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

interferon
iPSC-derived peripheral neurons
JAK/STAT
neuronal damage
SARM1
SARS-CoV-2

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