Nat Commun. 2018 Aug 16;9(1):3284. doi: 10.1038/s41467-018-05782-5.
Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus.
Kim DH1, Park ES1, Lee AR1, Park S1, Park YK1, Ahn SH1, Kang HS1, Won JH1, Ha YN1, Jae B1, Kim DS2, Chung WC3, Song MJ3, Kim KH4, Park SH5, Kim SH6, Kim KH7,8.
Author information
1
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea.
2
Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea.
3
Virus-Host Interactions Laboratory, Division of Biotechnology, Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
4
Department of Surgery, Uijeongbu St. Mary's Hospital, Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 11765, Republic of Korea.
5
Department of Anatomy, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea.
6
Laboratory of Cytokine Immunology, Veterinary School, Konkuk University, Seoul 05029, Republic of Korea.
7
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea. [email protected].
8
KU Open Innovation Center, Research Institute of Medical Sciences, Konkuk University, Seoul 05029, Republic of Korea. [email protected].
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.