Abstract
Introduction: Enterovirus D68 (EV-D68) primarily associated with respiratory disease; however, in some rare case, it can lead to neurological disease such as acute flaccid myelitis (AFM), affecting children under the age of 5. AFM patients showed lesions on magnetic resonance imaging (MRI) and cerebrospinal fluid pleocytosis has been observed. This indicates that inflammatory response diffused in grey matter. The aim of this study is to decipher the neuropathogenesis mechanism, molecular changes and pathways triggered by the EV-D68 infection in the human neuronal cells. Methods: We analyzed whole genome transcriptomic profiles of EV-D68 infected human neuroblastoma cells
(SK-N-SH) comparing with mock at each timepoint of 12 hours, 24 hours, and 48 hours. Results: Data revealed upregulation in pathways associated with immune and inflammatory response towards EV-D68 infection at each
timepoint. This finding showed the mechanism of EV-D68 in host immune signaling pathway. 24 genes in host cells significantly upregulated in the early stage of EV-D68 infection (12h) are BST2, CMPK2, DDX60, HELZ2, IFI27, IFI44,
IFI44L, IFI6, IFIT1, IFIT3, IFITM1, IRF7, IRF9, ISG15, MX2, OAS1, OAS2, OASL, PARP9, PLSCR1, REC8, RSAD2, STAT1, USP18. These genes are involved in pathways such as NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, RIG-1-like receptor signaling pathway, C-type lectin receptor signaling pathway and other immune pathways. EV-D68 infection induces upregulation of genes and mechanisms involved in immune response against EV-D68. One of the observed phenomena from AFM cases is cerebrospinal fluid pleocytosis, suggesting infection of EV-D68 may be the cause of diffuse immune response in grey matter. To reduce inflammation and immune response triggered by EV-D68, therapeutics targeting immune pathways associated with EV-D68 infection could be a potential antiviral strategy. Conclusion: EV-D68 infection results in the upregulation of genes, mechanisms, and pathways involved in immune responses in neuropathogenesis.
(SK-N-SH) comparing with mock at each timepoint of 12 hours, 24 hours, and 48 hours. Results: Data revealed upregulation in pathways associated with immune and inflammatory response towards EV-D68 infection at each
timepoint. This finding showed the mechanism of EV-D68 in host immune signaling pathway. 24 genes in host cells significantly upregulated in the early stage of EV-D68 infection (12h) are BST2, CMPK2, DDX60, HELZ2, IFI27, IFI44,
IFI44L, IFI6, IFIT1, IFIT3, IFITM1, IRF7, IRF9, ISG15, MX2, OAS1, OAS2, OASL, PARP9, PLSCR1, REC8, RSAD2, STAT1, USP18. These genes are involved in pathways such as NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, RIG-1-like receptor signaling pathway, C-type lectin receptor signaling pathway and other immune pathways. EV-D68 infection induces upregulation of genes and mechanisms involved in immune response against EV-D68. One of the observed phenomena from AFM cases is cerebrospinal fluid pleocytosis, suggesting infection of EV-D68 may be the cause of diffuse immune response in grey matter. To reduce inflammation and immune response triggered by EV-D68, therapeutics targeting immune pathways associated with EV-D68 infection could be a potential antiviral strategy. Conclusion: EV-D68 infection results in the upregulation of genes, mechanisms, and pathways involved in immune responses in neuropathogenesis.
| Original language | English |
|---|---|
| Article number | OP-23 |
| Pages (from-to) | 38 |
| Number of pages | 1 |
| Journal | Malaysian Journal of Medicine and Health Sciences |
| Volume | 20 |
| Issue number | Supp 4 |
| Publication status | Published - Jun 2024 |
| Event | International Conference on Integrative Physiology and Molecular Medicine 2024 - Hotel Casuarina, Ipoh, Malaysia Duration: 27 Feb 2024 → 29 Feb 2024 Conference number: 1st https://medic.upm.edu.my/upload/dokumen/20240607085100Complete_ICIPMM_2024.pdf https://medic.upm.edu.my/our_journal/volume_20_2024/mjmhs_vol20_supp_4_june_2024-79704 |
