title: Hepatitis B virus X protein is capable of down-regulating protein level of host antiviral protein APOBEC3G.
abstract: The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family proteins bind RNA and single-stranded DNA, and create C-to-U base modifications through cytidine deaminase activity. APOBEC3G restricts human immunodeficiency virus 1 (HIV-1) infection by creating hypermutations in proviral DNA, while HIV-1-encoded vif protein antagonizes such restriction by targeting APOBEC3G for degradation. APOBEC3G also inhibits hepatitis B virus (HBV): APOBEC3G co-expression inhibits HBV replication and evidences exist indicating APOBEC3G-mediated HBV hypermutations in patients. HBV encodes a small non-structural X protein (HBx) with a recognized activating effect on HBV life cycle. In this work, we report the discovery that HBx selectively and dose-dependently decreases the protein level of co-expressed APOBEC3G in transfected Huh-7 cells. The effect was shown to take place post-translationally, but does not rely on protein degradation via proteasome or lysosome. Further work demonstrated that intracellular APOBEC3G is normally exported via exosome secretion and inhibition of exosome biogenesis causes retention of intracellular APOBEC3G. Finally, HBx co-expression specifically enhanced externalization of APOBEC3G via exosomes, resulting in decrease of intracellular APOBEC3G protein level. These data suggest the possibility that in addition to other mechanisms, HBx-mediated activation of HBV might also involve antagonizing of intracellular restriction factor APOBEC3G through promotion of its export.
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.|Microbiology Laboratory, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D000071480:APOBEC-3G Deaminase / Q000235:genetics* / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D059748:Proteolysis; D012323:RNA Processing, Post-Transcriptional; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D000071480:APOBEC-3G Deaminase