Effects of interferon-α/β on HBV replication determined by viral load

PLoS Pathog. 2011 Jul;7(7):e1002159. doi: 10.1371/journal.ppat.1002159. Epub 2011 Jul 28.

Abstract

Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gene Expression Regulation, Viral / immunology
  • Hepatitis B / genetics
  • Hepatitis B / immunology*
  • Hepatitis B / metabolism
  • Hepatitis B virus / physiology*
  • Hepatocyte Nuclear Factor 3-gamma / genetics
  • Hepatocyte Nuclear Factor 3-gamma / immunology
  • Hepatocyte Nuclear Factor 3-gamma / metabolism
  • Interferon-alpha / immunology*
  • Interferon-alpha / metabolism
  • Interferon-beta / immunology*
  • Interferon-beta / metabolism
  • Mice
  • Mice, Transgenic
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology
  • Viral Load*
  • Virus Replication / immunology*

Substances

  • Foxa3 protein, mouse
  • Interferon-alpha
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Hepatocyte Nuclear Factor 3-gamma
  • Interferon-beta