Academic Journal

Human motor neurons derived from induced pluripotent stem cells are susceptible to SARS-CoV-2 infection

التفاصيل البيبلوغرافية
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
الوصف
تدمد:16625102
DOI:10.3389/fncel.2023.1285836