Infection, transport and degeneration of human neurons caused by severe acute respiratory syndrome coronavirus 2
Virology
Final Report Abstract
Overall, our results suggest that SARS-CoV-2 infects more efficiently sensory neurons than MSN. Infection of MSN did not induce ER stress, innate immunity nor neuronal damage. On the contrary, infection of sensory neurons induced high level of IFN-λ1, expression of ISGs, cytokines, ER-stress genes and genes involved in triggering neurodegeneration, like SARM1. There was also a reduction in transcripts and protein of cytoskeleton proteins, indicative of axonal damage. Inhibition of the JAK/STAT pathway reduced neuronal damage without increasing SARS-CoV-2 infection. The potential link between type III INF and neuronal damage during infection is understudied. To determine whether there is a direct of effect between high IFN-λ1 expression and neurite degeneration mediated by SARM1 upon SARS-CoV-2 infection requires further work. A considerable number of COVID-19 patients suffers from many symptoms associated with neuronal dysfunction in the PNS, including loss of innervation and increased neuropathy. Our results cannot explain the broad range of different neurological symptoms from which COVID-19 patients suffer, but they provide a model to further explore the role of SARS-CoV-2 infection and the innate immune response in the neuronal pathology and to test future preventive or therapeutic strategies.
Publications
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Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons. Cold Spring Harbor Laboratory.
Passos, Vania; Henkel, Lisa M.; Wang, Jiayi; Zapatero-Belinchón, Francisco J.; Möller, Rebecca; Sun, Guorong; Waltl, Inken; Ritter, Birgit; Kropp, Kai A.; Zhu, Shuyong; Deleidi, Michela; Kalinke, Ulrich; Höglinger, Günter; Gerold, Gisa; Wegner, Florian & Viejo-Borbolla, Abel
