The gene expression profile of peripheral blood mononuclear cells from EV71-infected rhesus infants and the significance in viral pathogenesis

PLoS One. 2014 Jan 2;9(1):e83766. doi: 10.1371/journal.pone.0083766. eCollection 2014.

Abstract

Enterovirus 71 (EV71) is the major pathogen responsible for fatal hand, foot and mouth disease (HFMD). Our previous work reported on an EV71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (CNS) and lungs. This study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) from EV71-infected rhesus monkey infants. The expression of more than 500 functional genes associated with multiple pathways was modulated. The expression of genes associated with immune inflammatory responses was up-regulated during the period from days 4 to 10 post-infection. The expression of two genes (TAC1 and IL17A), which play major roles in inflammatory reactions, was remarkably up-regulated during the infection period. Furthermore, a higher expression level of the TAC1 gene was identified in the CNS compared to the lungs, but a high expression level of the IL-17A gene was observed in the lungs and not in the CNS. The results of this study suggest at least two facts about EV71 infection, which are that: the TAC1 gene that encodes substance P and neurokinin-A is present in both PBMCs and the hypothalamus; and the up-regulation of IL-17A is sustained in the peripheral blood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / metabolism
  • Central Nervous System / virology
  • Cluster Analysis
  • Enterovirus A, Human / physiology*
  • Enterovirus Infections / genetics*
  • Enterovirus Infections / immunology
  • Enterovirus Infections / virology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hand, Foot and Mouth Disease / genetics
  • Hand, Foot and Mouth Disease / immunology
  • Hand, Foot and Mouth Disease / virology
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-17 / genetics
  • Leukocytes, Mononuclear / metabolism*
  • Macaca mulatta
  • Transcriptome*

Substances

  • Interleukin-17

Grants and funding

This work was supported by the National Basic Research Program (2011CB504903 and 2012CB518901), National High-Tech R&D Program (2012AA02A404), National Natural Sciences Foundation of China (81171573 and 31100127), the Yunnan Natural Science Foundation (2011FB116) and Youth Foundation of Peking Union Medical College (3332013083). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.