Methyltransferase of a cell culture-adapted hepatitis E inhibits the MDA5 receptor signaling pathway

J Microbiol. 2019 Dec;57(12):1126-1131. doi: 10.1007/s12275-019-9478-8. Epub 2019 Nov 22.

Abstract

Hepatitis E virus (HEV) is a causative agent of acute hepatitis and jaundice. The number of human infections is approximated to be over 20 million cases per year. The transmission is mainly via the fecal-oral route and contaminated water and food are considered to be a major source of infection. As a mouse model is not available, a recent development of a cell culture-adapted HEV strain (47832c) is considered as a very important tools for molecular analysis of HEV pathogenesis in cells. Previously, we demonstrated that HEV-encoded methyltransferase (MeT) encoded by the 47832c strain inhibits MDA5- and RIG-I-mediated activation of interferon β (IFN-β) promoter. Here, we report that MeT impairs the phosphorylation and activation of interferon regulatory factor 3 and the p65 subunit of NF-κB in a dose-dependent manner. In addition, the MeT encoded by the 47832c, but not that of HEV clinical or field isolates (SAR-55, Mex-14, KC-1, and ZJ-1), displays the inhibitory effect. A deeper understanding of MeTmediated suppression of IFN-β expression would provide basis of the cell culture adaptation of HEV.

Keywords: hepatitis E virus; interferon; methyltransferase.

MeSH terms

  • Animals
  • Cell Culture Techniques
  • DEAD Box Protein 58 / drug effects
  • DEAD Box Protein 58 / metabolism
  • Disease Models, Animal
  • HEK293 Cells
  • Hepatitis E / virology
  • Hepatitis E virus / enzymology
  • Hepatitis E virus / pathogenicity
  • Hepatitis E virus / physiology*
  • Humans
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon-Induced Helicase, IFIH1 / drug effects*
  • Interferon-Induced Helicase, IFIH1 / metabolism*
  • Interferon-beta / metabolism
  • Methyltransferases / antagonists & inhibitors*
  • Methyltransferases / metabolism*
  • Mice
  • NF-kappa B / metabolism
  • Phosphorylation
  • Receptors, Immunologic
  • Signal Transduction / physiology*

Substances

  • Interferon Regulatory Factor-3
  • NF-kappa B
  • Receptors, Immunologic
  • Interferon-beta
  • Methyltransferases
  • RIGI protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • Interferon-Induced Helicase, IFIH1