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Differential Regulation of Host Genes Including Hepatic Fatty Acid Synthase in HBV-Transgenic Mice
journal contribution
posted on 2013-06-07, 00:00 authored by Hongmin Zhang, Hong Li, Yixuan Yang, Sanglin Li, Hong Ren, Dazhi Zhang, Huaidong HuHepatitis 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.