Tumor Necrosis Factor Alpha Inhibition of Hepatitis B Virus Replication Involves Disruption of Capsid Integrity through Activation of NF-κB

• Michael Biermer

  Department of Microbiology, New York University School of Medicine, New York, New York 10016

• Robyn Puro

  Department of Microbiology, New York University School of Medicine, New York, New York 10016

• Robert J. Schneider

  Department of Microbiology, New York University School of Medicine, New York, New York 10016

抄録

Chronic infection by hepatitis B virus results from an inability to clear the virus, which is associated with liver disease and liver cancer. Tumor necrosis factor alpha (TNF-α) is associated with noncytopathic clearance of hepatitis B virus in animal models. Here we demonstrate that the nuclear factor κB (NF-κB) signaling pathway is a central mediator of inhibition of hepatitis B virus by TNF-α and we describe the molecular mechanism. TNF-α is shown to suppress hepatitis B virus DNA replication without cell killing by disrupting the formation or stability of cytoplasmic viral capsids through a pathway requiring the NF-κB-activating inhibitor of κB kinase complex IKK-α/β and active transcription factor NF-κB. Hepatitis B virus replication could also be inhibited and viral capsid formation could be disrupted in the absence of TNF-α solely by overexpression of IKK-α/β or strong activation of NF-κB. In contrast, inhibition of NF-κB signaling stimulated viral replication, demonstrating that HBV replication is both positively and negatively regulated by the level of activity of the NF-κB pathway. Studies are presented that exclude the possibility that HBV inhibition by NF-κB is carried out by secondary production of gamma interferon or alpha/beta interferon. These results identify a novel mechanism for noncytopathic suppression of hepatitis B virus replication that is mediated by the NF-κB signaling pathway and activated by TNF-α.

収録刊行物

• Journal of Virology

  Journal of Virology 77 (7), 4033-4042, 2003-04

  American Society for Microbiology

キーワード

• Virology
• Insect Science
• Immunology
• Microbiology

詳細情報

• CRID: 1360861711229101696
• NII論文ID: 30020797940
• DOI: 10.1128/jvi.77.7.4033-4042.2003
• ISSN: 10985514
• ISSN: 0022538X
• Web Site: https://journals.asm.org/doi/pdf/10.1128/JVI.77.7.4033-4042.2003
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