Affiliations 

  • 1 Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore
  • 2 National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom
  • 3 Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
  • 4 Institute of Health and Community Medicine, University Malaysia Sarawak, Sarawak, Malaysia
  • 5 Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore. Julian.Hiscox@liverpool.ac.uk
  • 6 Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore. lisa_ng@immunol.a-star.edu.sg
Sci Rep, 2020 03 02;10(1):3810.
PMID: 32123257 DOI: 10.1038/s41598-020-60761-5

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.