title: Human hepatitis B virus surface and e antigens inhibit major vault protein signaling in interferon induction pathways.
abstract: OBJECTIVE
  We previously demonstrated that major vault protein (MVP) is a novel virus-induced host factor and its expression upregulates type-I interferon production, leading to cellular antiviral response. However, it remains unclear whether the antiviral function of MVP is impaired during hepatitis B virus (HBV) infection and what mechanisms are involved. Therefore, the aim of this study was to assess whether HBV can alter MVP expression despite the lack of type-I IFN induction and shed light on the underlying mechanisms HBV utilizes to evade host innate immune response.
  
  
  METHODS
  The ability of HBV surface and e antigens to inhibit MVP signaling in interferon induction pathways was evaluated by co-immunoprecipitation, immunofluorescence, quantitative RT-PCR, Western blot and reporter assays.
  
  
  RESULTS
  In our current study, we found high levels of MVP in peripheral blood mononuclear cells, sera, and liver tissue from HBV-infected patients relative to healthy individuals. We determined that MVP intracellularly associates with MyD88, an adapter protein involved in virus-triggered induction of type-I IFN. Protein truncation analysis revealed that the middle domain of MVP (amino acid residues 310-620) was essential for MyD88 binding. Conversely, HBV inhibited MVP-induced type-I IFN production by suppressing MVP/MyD88 interaction. HBV antigens, both HBsAg and HBeAg, suppressed this interaction by competitively binding to the essential MyD88 binding region of MVP and limiting downstream IFN signaling.
  
  
  CONCLUSIONS
  MVP is a virus-induced protein capable of binding with MyD88 leading to type-I IFN production. HBV may evade an immune response by disrupting this interaction and limiting type-I IFN antiviral activity.
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Nanfang
authors.initials: N
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Zhangchuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Fanpeng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: yingzhu@whu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D006509:Hepatitis B / Q000276:immunology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis*; D008099:Liver / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007370:Interferon Type I; D053594:Myeloid Differentiation Factor 88; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C507779:MYD88 protein, human
keywords: Immune evasion; Major vault protein; MyD88; Viral infection