Citation

  • Authors: Kim, D. H., Park, E. S., Lee, A. R., Park, S., Park, Y. K., Ahn, S. H., Kang, H. S., Won, J. H., Ha, Y. N., Jae, B., Kim, D. S., Chung, W. C., Song, M. J., Kim, K. H., Park, S. H., Kim, S. H., Kim, K. H.
  • Year: 2018
  • Journal: Nat Commun 9 3284
  • Applications: in vitro / DNA / jetPEI-Hepatocyte
  • Cell types:
    1. Name: Human primary hepatocytes
      Description: Primary human hepatocytes
    2. Name: Mouse primary hepatocytes
      Description: Primary mouse hepatocytes

Abstract

Cytokines are involved in early host defense against pathogen infections. In particular, tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) have critical functions in non-cytopathic elimination of hepatitis B virus (HBV) in hepatocytes. However, the molecular mechanisms and mediator molecules are largely unknown. Here we show that interleukin-32 (IL-32) is induced by TNF and IFN-gamma in hepatocytes, and inhibits the replication of HBV by acting intracellularly to suppress HBV transcription and replication. The gamma isoform of IL-32 (IL-32gamma) inhibits viral enhancer activities by downregulating liver-enriched transcription factors. Our data are validated in both an in vivo HBV mouse model and primary human hepatocytes. This study thus suggests that IL-32gamma functions as intracellular effector in hepatocytes for suppressing HBV replication to implicate a possible mechanism of non-cytopathic viral clearance.

Pubmed