title: Interleukin-15 suppresses hepatitis B virus replication via IFN-β production in a C57BL/6 mouse model.
abstract: BACKGROUND
  Interleukin-15 (IL-15) is a pleiotropic cytokine known to modulate both innate and adaptive immunity. It is suggested that IL-15 may play an important role in the regulation of immune response to hepatitis B virus (HBV).
  
  
  OBJECTIVE
  We investigated whether IL-15 could modulate the immune response to HBV.
  
  
  METHODS
  A mouse model for HBV tolerance was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. This HBV-carrier mouse was simultaneously hydrodynamically injected with either an IL-15-expression plasmid pLIVE-IL-15 or a mock control vector pLIVE-EGFP. The serum levels of HBsAg and HBeAg were measured by radioimmunoassay.
  
  
  RESULTS
  Hydrodynamic injection of the plasmid pLIVE-IL-15 resulted in sustained high level of IL-15 in mouse serum, along with the markedly decreased serum HBsAg and HBeAg titres and liver HBV DNA levels. IL-15 also induced anti-HBV activity in T cell- and B cell-deficient Rag1(-/-)  mice. Interestingly, despite an increase in NK cell numbers in both spleen and liver of IL-15 treated mice, the anti-HBV effect of IL-15 was neither dependent on presence of NK cells nor on production of IFN-γ. Furthermore, IL-15 could exert anti-HBV function independent of the common IL-2γ(c) R. Lastly, we found that IFN-β expression in the liver and serum was significantly up-regulated by liver expression of IL-15, and blockade of IFN-β function abrogated the anti-HBV activity of IL-15.
  
  
  CONCLUSIONS
  Liver over-expression of IL-15 may suppress HBV replication in an IFN-β-dependent manner.
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Yin
authors.forename: Long
authors.initials: L
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010957:Plasmids / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; C064658:RAG-1 protein; D016899:Interferon-beta; D007371:Interferon-gamma