Suppression of hepatitis B virus replication in Tupaia hepatocytes by tumor necrosis factor alpha of Tupaia belangeri

Comp Immunol Microbiol Infect Dis. 2011 Jul;34(4):361-8. doi: 10.1016/j.cimid.2011.05.003. Epub 2011 Jun 28.

Abstract

Recently, Tupaia belangeri was used to study the full replication cycle of hepatitis B virus (HBV) in the primary hepatocyte cultures. Thus, the Tupaia model represents a suitable model to study the effects of cytokines on HBV infection. Here, Tupaia tumor necrosis factor-alpha (TNF-α) was molecularly cloned and expressed in mammalian cells. A test system for the biological activity of Tupaia TNF-α was established on the basis of its cytotoxic effect to the murine fibrosarcoma cell line L929. Recombinant Tupaia TNF-α was able to suppress HBV replication in primary Tupaia hepatocytes (PTH). However, the formation of HBV covalently closed circular DNA (cccDNA) and viral RNA was not completely prevented. Therefore, Tupaia TNF-α may contribute significantly to the control of HBV infection though it is not able to completely inhibit HBV replication alone. The characterization of this important cytokine allows further studies on its antiviral actions in the Tupaia model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacology*
  • Carcinoma, Hepatocellular
  • DNA, Circular / analysis
  • DNA, Viral / analysis
  • Fibrosarcoma
  • Hepatitis B / genetics
  • Hepatitis B / immunology
  • Hepatitis B / pathology
  • Hepatitis B / virology
  • Hepatitis B virus* / drug effects
  • Hepatitis B virus* / growth & development
  • Hepatitis B virus* / immunology
  • Hepatocytes / drug effects*
  • Hepatocytes / immunology
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Humans
  • Mice
  • Models, Animal
  • Plasmids
  • Primary Cell Culture
  • RNA, Viral / analysis
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tupaia* / genetics
  • Tupaia* / immunology
  • Tupaia* / virology
  • Virus Replication / drug effects*
  • Virus Replication / genetics
  • Virus Replication / immunology

Substances

  • Antiviral Agents
  • DNA, Circular
  • DNA, Viral
  • RNA, Viral
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha