Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus

Doo Hyun Kim, Eun Sook Park, Ah Ram Lee, Soree Park, Yong Kwang Park, Sung Hyun Ahn, Hong Seok Kang, Ju Hee Won, Yea Na Ha, Byeong June Jae, Dong-Sik Kim, Woo Chang Chung, Moon Jung Song, Kee Hwan Kim, Seung Hwa Park, Soo Hyun Kim, Kyun Hwan Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cytokines are involved in early host defense against pathogen infections. In particular, tumor necrosis factor (TNF) and interferon-gamma (IFN-γ) 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-γ in hepatocytes, and inhibits the replication of HBV by acting intracellularly to suppress HBV transcription and replication. The gamma isoform of IL-32 (IL-32γ) 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-32γ functions as intracellular effector in hepatocytes for suppressing HBV replication to implicate a possible mechanism of non-cytopathic viral clearance.

Original languageEnglish
Article number3284
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

    Fingerprint

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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. J., Kim, D-S., Chung, W. C., Song, M. J., Kim, K. H., Park, S. H., Kim, S. H., & Kim, K. H. (2018). Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus. Nature Communications, 9(1), [3284]. https://doi.org/10.1038/s41467-018-05782-5