title: Differential regulation of host genes including hepatic fatty acid synthase in HBV-transgenic mice.
abstract: Hepatitis B virus (HBV) is the most common of the hepatitis viruses that cause chronic liver infections in humans, and it is considered to be a major global health problem. To gain a better understanding of HBV pathogenesis, and identify novel putative targets for anti-HBV therapy, this study was designed to elucidate the differential expression of host proteins in liver tissue from HBV-transgenic mice. Liver samples from two groups, (1) HBV-transgenic (Tg) mice, (2) corresponding background normal mice, wild-type (WT) mice, were collected and subjected to iTRAQ and mass spectrometry analysis. In total, 1950 unique proteins were identified, and 68 proteins were found to be differentially expressed in HBV-Tg mice as compared with that in WT mice. Several differentially expressed proteins were further validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analysis. Furthermore, the association of HBV replication with fatty acid synthase (FASN), one of the highly expressed proteins in HBV-Tg mice, was verified. Silencing of FASN expression in HepG2.2.15 cells suppressed viral replication through the IFN signaling pathway, and some downstream antiviral effectors. The implicated role of FASN in HBV replication provides an opportunity to test existing compounds against FASN for adjuvant therapy and/or treatment of HBV replication.
authors.affiliation: Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Sanglin
authors.initials: S
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000821:virology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020543:Proteome / Q000032:analysis*; D015398:Signal Transduction; D014779:Virus Replication / Q000502:physiology
chemical_list: D020543:Proteome; D054890:Fatty Acid Synthase, Type I