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SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis.
Gugliandolo, Agnese; Chiricosta, Luigi; Calcaterra, Valeria; Biasin, Mara; Cappelletti, Gioia; Carelli, Stephana; Zuccotti, Gianvincenzo; Avanzini, Maria Antonietta; Bramanti, Placido; Pelizzo, Gloria; Mazzon, Emanuela.
  • Gugliandolo A; IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
  • Chiricosta L; IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
  • Calcaterra V; Department of Pediatrics, Ospedale dei Bambini "Vittore Buzzi", 20154 Milano, Italy.
  • Biasin M; Pediatrics and Adolescentology Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy.
  • Cappelletti G; Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy.
  • Carelli S; Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy.
  • Zuccotti G; Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, 20157 Milan, Italy.
  • Avanzini MA; Department of Pediatrics, Ospedale dei Bambini "Vittore Buzzi", 20154 Milano, Italy.
  • Bramanti P; Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy.
  • Pelizzo G; Cell Factory, Pediatric Hematology Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
  • Mazzon E; IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Int J Mol Sci ; 22(15)2021 Jul 28.
Article in English | MEDLINE | ID: covidwho-1335097
ABSTRACT
Different mechanisms were proposed as responsible for COVID-19 neurological symptoms but a clear one has not been established yet. In this work we aimed to study SARS-CoV-2 capacity to infect pediatric human cortical neuronal HCN-2 cells, studying the changes in the transcriptomic profile by next generation sequencing. SARS-CoV-2 was able to replicate in HCN-2 cells, that did not express ACE2, confirmed also with Western blot, and TMPRSS2. Looking for pattern recognition receptor expression, we found the deregulation of scavenger receptors, such as SR-B1, and the downregulation of genes encoding for Nod-like receptors. On the other hand, TLR1, TLR4 and TLR6 encoding for Toll-like receptors (TLRs) were upregulated. We also found the upregulation of genes encoding for ERK, JNK, NF-κB and Caspase 8 in our transcriptomic analysis. Regarding the expression of known receptors for viral RNA, only RIG-1 showed an increased expression; downstream RIG-1, the genes encoding for TRAF3, IKKε and IRF3 were downregulated. We also found the upregulation of genes encoding for chemokines and accordingly we found an increase in cytokine/chemokine levels in the medium. According to our results, it is possible to speculate that additionally to ACE2 and TMPRSS2, also other receptors may interact with SARS-CoV-2 proteins and mediate its entry or pathogenesis in pediatric cortical neurons infected with SARS-CoV-2. In particular, TLRs signaling could be crucial for the neurological involvement related to SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cerebral Cortex / Toll-Like Receptors / SARS-CoV-2 / COVID-19 / Neurons Type of study: Etiology study Limits: Child / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22158059

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cerebral Cortex / Toll-Like Receptors / SARS-CoV-2 / COVID-19 / Neurons Type of study: Etiology study Limits: Child / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22158059