Different antiviral effects of IFNα and IFNβ in an HBV mouse model

Immunobiology. 2017 Mar;222(3):562-570. doi: 10.1016/j.imbio.2016.11.003. Epub 2016 Nov 8.

Abstract

Interferons α and β (IFNα and IFNβ) are type I interferons produced by the host to control pathogen propagation. However, only a minority of chronic hepatitis B (CHB) patients generate a sustained response after treatment with recombinant IFNα. The anti-HBV effect of IFNβ and the underlying mechanism are not well-understood. Here, we compared the antiviral activities of IFNα and IFNβ by application of IFNα or IFNβ expression plasmids using the well-established HBV hydrodynamic injection (HI) mouse model. Injection of IFNα expression plasmid could significantly reduce HBV serum markers including HBsAg, HBeAg and HBV DNA as well as the number of HBcAg positive cells in the liver, while IFNβ showed only a weak inhibition of HBV replication. In contrast to IFNβ, IFNα resulted in elevated expression levels of IFN stimulated genes (ISGs) as well as the proinflammatory cytokine interleukin 6 (IL6) in the liver. Moreover, IFNβ treated mice showed higher expression levels of the anti-inflammatory cytokines IL10 and TGFβ in the liver compared to IFNα. Our results demonstrated that both IFNα and IFNβ exert antiviral activities against HBV in HI mouse model, but IFNα is more effective than IFNβ.

Keywords: Antiviral effect; HBV mouse model; IFNα; IFNβ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents* / pharmacology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Gene Expression
  • Gene Transfer Techniques
  • Hepatitis B / drug therapy
  • Hepatitis B / genetics*
  • Hepatitis B / virology*
  • Hepatitis B Core Antigens / blood
  • Hepatitis B Core Antigens / genetics
  • Hepatitis B virus / classification
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Humans
  • Interferon-alpha / blood
  • Interferon-alpha / genetics*
  • Interferon-alpha / pharmacology
  • Interferon-beta / blood
  • Interferon-beta / genetics*
  • Interferon-beta / pharmacology
  • Liver / metabolism
  • Liver / pathology
  • Liver / virology
  • Mice
  • Plasmids / administration & dosage
  • Plasmids / genetics
  • RNA, Messenger / genetics
  • Transfection
  • Ubiquitins / genetics
  • Ubiquitins / metabolism
  • Viral Load
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Cytokines
  • G1p2 protein, mouse
  • Hepatitis B Core Antigens
  • Interferon-alpha
  • RNA, Messenger
  • Ubiquitins
  • Interferon-beta