title: APOBEC3-independent interferon-induced viral clearance in hepatitis B virus transgenic mice.
abstract: Interferon (IFN) has been part of the standard treatment of chronic hepatitis B infection for more than 2 decades, yet the mechanism of action of this antiviral remains poorly understood. It was recently observed that members of the human APOBEC family of cytidine deaminases endowed with anti-hepatitis B virus (HBV) activity are upregulated by type I and II IFNs. However, we demonstrated that, in tissue culture, these cellular enzymes are not essential effectors of the anti-HBV action of these cytokines. Here, we show that murine APOBEC3 (muA3) can also block HBV replication. While expressed at low levels in the mouse liver at baseline, muA3 is upregulated upon IFN induction. However, in HBV-transgenic muA3 knockout mice, IFN induction blocked HBV DNA production as efficiently as in control HBV-transgenic muA3-competent animals. We conclude that APOBEC3 is not an essential mediator of the IFN-mediated inhibition of HBV in vivo.
authors.affiliation: Global Health Institute, School of Life Sciences and Frontiers in Genetics National Center for Competence in Research, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Turelli
authors.forename: Alexandra
authors.initials: A
authors.lastname: Liagre-Quazzola
authors.forename: Bastien
authors.initials: B
authors.lastname: Mangeat
authors.forename: Sonia
authors.initials: S
authors.lastname: Verp
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jost
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology*; D006515:Hepatitis B virus; D047468:Immunoprecipitation; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics*
chemical_list: D017931:DNA Primers; D007372:Interferons; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase