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. Cytokines such as TNF and IFN-γ are important for immunity against hepatitis B virus (HBV). Here the authors show that interleukin-32 gamma (IL-32γ) acts downstream of TNF and IFN-γ as an intracellular effector, and that IL-32γ negatively regulates host factors contributing to HBV transcription to promote HBV clearance.
Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus
[Category] B형 간염, Fulltext,
[Article Type] Article
[Source] PMC
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