title: Effects of interferon-α/β on HBV replication determined by viral load.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tian
authors.forename: Wen-ling
authors.initials: WL
authors.lastname: Chen
authors.forename: Jing-hsiung James
authors.initials: JH
authors.lastname: Ou
mesh_terms: D000818:Animals; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology*; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism; D016899:Interferon-beta / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*
chemical_list: C496506:Foxa3 protein, mouse; D016898:Interferon-alpha; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051543:Hepatocyte Nuclear Factor 3-gamma; D016899:Interferon-beta