The RNA sensor RIG-I dually functions as an innate sensor and direct antiviral factor for hepatitis B virus

Immunity. 2015 Jan 20;42(1):123-32. doi: 10.1016/j.immuni.2014.12.016. Epub 2014 Dec 18.

Abstract

Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but not type I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-ε region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this ε region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate-recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Child, Preschool
  • Female
  • Gene Products, pol / antagonists & inhibitors*
  • Hep G2 Cells
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / immunology*
  • Hepatocytes / physiology*
  • Hepatocytes / transplantation
  • Hepatocytes / virology
  • Humans
  • Immunity, Innate
  • Interferons / metabolism
  • Liver / physiology*
  • Liver / virology
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, SCID
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / immunology*
  • Transgenes / genetics
  • Transplantation Chimera
  • Virus Replication / genetics

Substances

  • Gene Products, pol
  • Membrane Proteins
  • Nerve Tissue Proteins
  • P protein, Hepatitis B virus
  • RNA, Viral
  • Robo3 protein, mouse
  • Interferons