SARS-CoV-2 infected pediatric cerebral cortical neurons: transcriptomic analysis and potential role of Toll-like receptors in pathogenesis

To date, it is not clear if SARS-CoV-2 can infect neuronal cells. 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. HCN-2 cells did not express ACE2 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 contrary, TLR1, TLR4 and TLR6 encoding for Toll-like receptors(TLRs) were upregulated. We also found the upregulation of genes encoding for ERK, JNK, NF-kB and Caspase 8 in our transcriptomic analysis. Regarding the expression of known receptor for viral RNA, only RIG-1 showed an increased expression; downstream RIG-1, the genes encoding for TRAF3, IKKe, 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.