Amrun, Siti Naqiah, Tan, Jeslin JL, Rickett, Natasha Y, Cox, Jonathan A, Lee, Bernett, Griffiths, Michael J, Solomon, Tom 
ORCID: 0000-0001-7266-6547, Perera, David, Ooi, Mong How, Hiscox, Julian A ORCID: 0000-0002-6582-0275 et al (show 1 more authors)
(2020)
TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection.
SCIENTIFIC REPORTS, 10 (1).
3810-.
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TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection.pdf - Published version Download (4MB) | Preview |
Abstract
Hand, foot and mouth disease (HFMD), caused by enterovirus A71 (EV-A71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV-A71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterised in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV-A71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV-A71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signalling. Depletion of TREM-1 in EV-A71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV-A71 infections in primary human cells, and the potential involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | B-Lymphocytes, T-Lymphocytes, Monocytes, Cell Line, Tumor, Humans, Enterovirus A, Human, Enterovirus Infections, Phylogeny, Gene Expression Regulation, Triggering Receptor Expressed on Myeloid Cells-1 |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 24 Apr 2020 14:22 |
| Last Modified: | 18 Jan 2023 23:54 |
| DOI: | 10.1038/s41598-020-60761-5 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3083998 |
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