Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a

Sci Rep. 2016 May 23;6:26150. doi: 10.1038/srep26150.

Abstract

Previous studies showed that hepatitis B virus (HBV), as a latency invader, attenuated host anti-viral immune responses. miRNAs were shown to be involved in HBV infection and HBV-related diseases, however, the precise role of miRNAs in HBV-mediated immunosuppression remains unclear. Here, we observed that down-regulated RIG-I like receptors might be one critical mechanism of HBV-induced suppression of type I IFN transcription in both HBV(+) hepatoma cell lines and liver cancer tissues. Then, miR146a was demonstrated to negatively regulate the expression of RIG-I-like receptors by directly targeting both RIG-I and RIG-G. Further investigation showed that antagonizing miR146a by anti-sense inhibitors or sponge approach accelerated HBV clearance and reduced HBV load both in vitro and in a HBV-carrying mouse model. Therefore, our findings indicated that HBV-induced miR146a attenuates cell-intrinsic anti-viral innate immunity through targeting RIG-I and RIG-G, and silencing miR146a might be an effective target to reverse HBV-induced immune suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DEAD Box Protein 58
  • Disease Models, Animal
  • Hepatitis B / immunology
  • Hepatitis B / virology
  • Hepatitis B virus / physiology*
  • Hepatocytes / immunology
  • Hepatocytes / virology
  • Host-Pathogen Interactions*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • MicroRNAs
  • Signal Transduction

Substances

  • IFIT3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN146 microRNA, human
  • MicroRNAs
  • DDX58 protein, human
  • DEAD Box Protein 58