Academic Journal
Human motor neurons derived from induced pluripotent stem cells are susceptible to SARS-CoV-2 infection
| العنوان: | Human motor neurons derived from induced pluripotent stem cells are susceptible to SARS-CoV-2 infection |
|---|---|
| المؤلفون: | Gioia Cappelletti, Claudia Colombrita, Fiona Limanaqi, Sabrina Invernizzi, Micaela Garziano, Claudia Vanetti, Claudia Moscheni, Serena Santangelo, Silvia Zecchini, Daria Trabattoni, Vincenzo Silani, Mario Clerici, Antonia Ratti, Mara Biasin |
| المصدر: | Frontiers in Cellular Neuroscience, Vol 17 (2023) |
| بيانات النشر: | Frontiers Media S.A., 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| مصطلحات موضوعية: | SARS-CoV-2 infection, iPSC-derived motor neurons, long-COVID, neuroinflammation, neuromuscular disorders, COVID-19, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| الوصف: | IntroductionCOVID-19 typically causes Q7 respiratory disorders, but a high proportion of patients also reports neurological and neuromuscular symptoms during and after SARSCoV-2 infection. Despite a number of studies documenting SARS-CoV-2 infection of various neuronal cell populations, the impact of SARS-CoV-2 exposure on motor neuronal cells specifically has not been investigated so far.MethodsThus, by using human iPSC-derived motor neurons (iPSC-MNs) we assessed: (i) the expression of SARS-CoV-2 main receptors; (ii) iPSC-MN infectability by SARS-CoV-2; and (iii) the effect of SARS-CoV-2 exposure on iPSC-MN transcriptome.ResultsGene expression profiling and immunofluorescence (IF) analysis of the main host cell receptors recognized by SARS-CoV-2 revealed that all of them are expressed in iPSC-MNs, with CD147 and NRP1 being the most represented ones. By analyzing SARS-CoV-2 N1 and N2 gene expression over time, we observed that human iPSC-MNs were productively infected by SARS-CoV-2 in the absence of cytopathic effect. Supernatants collected from SARS-CoV-2-infected iPSC-MNs were able to re-infect VeroE6 cells. Image analyses of SARS-CoV-2 nucleocapsid proteins by IF confirmed iPSC-MN infectability. Furthermore, SARS-CoV-2 infection in iPSCMNs significantly altered the expression of genes (IL-6, ANG, S1PR1, BCL2, BAX, Casp8, HLA-A, ERAP1, CD147, MX1) associated with cell survival and metabolism, as well as antiviral and inflammatory response.Discussion:These results suggest for the very first time that SARS-CoV-2 can productively infect human iPSC-derived MNs probably by binding CD147 and NRP1 receptors. Such information will be important to unveil the biological bases of neuromuscular disorders characterizing SARS-CoV-2 infection and the so called long-COVID symptoms. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1662-5102 |
| Relation: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1285836/full; https://doaj.org/toc/1662-5102 |
| DOI: | 10.3389/fncel.2023.1285836 |
| URL الوصول: | https://doaj.org/article/751f6a5cda9c484892f8fea6960ed350 |
| رقم الانضمام: | edsdoj.751f6a5cda9c484892f8fea6960ed350 |
| قاعدة البيانات: | Directory of Open Access Journals |
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