title: Hepatitis B virus upregulates host expression of α-1,2-mannosidasesviathe PPARα pathway.
abstract: OBJECTIVE
  To assess the effects of hepatitis B virus (HBV) on the expression of host α-1,2-mannosidases and determine the underlying mechanisms.
  
  
  METHODS
  We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot. Viral antigens (HBsAg and HBeAg) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit. Protein levels of human liver tissue α-1,2-mannosidases were also evaluated by Western blot. Plasmids containing seven individual viral genes of HBV (PTT22-HBx, PTT22-HBs, PTT22-preS2, PTT22-preS1, PTT22-HBc, PTT22-HBe, and PTT22-HBp) or control plasmids (PTT22-vector) were transfected into HepG2 cells. MK886 (PPARα) and GW9662 (PPARγ) inhibitors were used to explore the effects of HBV on α-1,2-mannosidase expression after the PPARα and PPARγ pathways were blocked.
  
  
  RESULTS
  We showed that the expression of α-1,2-mannosidases was higher in stably transfected HBV cells than in controls. The expression levels of α-1,2-mannosidase were higher in AD38 cells than those in ND10 cells, which were in turn greater than those in G2.2.15 cells, and positively correlated with the expression of HBsAg in all the cell lines. Levels of α-1,2-mannosidase in non-tumorous liver tissues of HBV-related HCC patients were also higher than in the tissues from non-HBV-related HCC patients. Moreover, transfecting HepG2 cells with a component of the HBV viral envelope also increased the expression of α-1,2-mannosidases. However, this envelope protein component could not induce MAN1C1 expression in the presence of a PPARα inhibitor, MK886. We also found that MK886 did not affect the expression of MAN1C1 in AD38 cells without tetracycline in the culture medium. This phenomenon was not observed in the case of GW9662.
  
  
  CONCLUSIONS
  Our results indicate that HBV increases the expression of α-mannosidases bothin vitroandin vivo viaactivation of the PPARα pathway by its envelope protein.
authors.affiliation: Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Song
authors.initials: S
authors.lastname: Hu
authors.affiliation: Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Jiang
authors.affiliation: Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Zou
authors.affiliation: Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Song Hu, Li-Bin Jiang, Xiao-Jing Zou, Wei Yi, De-Ying Tian, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: De-Ying
authors.initials: DY
authors.lastname: Tian
mesh_terms: D056945:Hep G2 Cells; D006509:Hepatitis B / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000821:virology*; D047493:PPAR alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D043323:alpha-Mannosidase / Q000378:metabolism*; D002722:Chlorobenzenes
chemical_list: D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007211:Indoles; D047493:PPAR alpha; D043323:alpha-Mannosidase; C060893:MK-886; D002722:Chlorobenzenes
keywords: Dendritic cells; Glycosylation; Hepatitis B; Pattern recognition receptors; α-Mannosidase