title: Interferons accelerate decay of replication-competent nucleocapsids of hepatitis B virus.
abstract: Alpha interferon (IFN-alpha) is an approved medication for chronic hepatitis B. Gamma interferon (IFN-gamma) is a key mediator of host antiviral immunity against hepatitis B virus (HBV) infection in vivo. However, the molecular mechanism by which these antiviral cytokines suppress HBV replication remains elusive. Using an immortalized murine hepatocyte (AML12)-derived cell line supporting tetracycline-inducible HBV replication, we show in this report that both IFN-alpha and IFN-gamma efficiently reduce the amount of intracellular HBV nucleocapsids. Furthermore, we provide evidence suggesting that the IFN-induced cellular antiviral response is able to distinguish and selectively accelerate the decay of HBV replication-competent nucleocapsids but not empty capsids in a proteasome-dependent manner. Our findings thus reveal a novel antiviral mechanism of IFNs and provide a basis for a better understanding of HBV pathobiology.
authors.affiliation: Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA 18902, USA.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Xu
authors.forename: Haitao
authors.initials: H
authors.lastname: Guo
authors.forename: Xiao-Ben
authors.initials: XB
authors.lastname: Pan
authors.forename: Richeng
authors.initials: R
authors.lastname: Mao
authors.forename: Wenquan
authors.initials: W
authors.lastname: Yu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xu
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Jinhong
authors.initials: J
authors.lastname: Chang
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Block
authors.forename: Ju-Tao
authors.initials: JT
authors.lastname: Guo
mesh_terms: D000818:Animals; D002460:Cell Line; D006515:Hepatitis B virus / Q000276:immunology*; D022781:Hepatocytes / Q000821:virology; D016898:Interferon-alpha / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D019251:Nucleocapsid / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex