Premium
Fatty acids increase hepatitis B virus X protein stabilization and HB x‐induced inflammatory gene expression
Author(s) -
Cho Hyun Kook,
Kim So Young,
Yoo Seong Keun,
Choi Yung Hyun,
Cheong JaeHun
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12776
Subject(s) - fatty liver , inflammation , chemistry , fatty acid , biology , microbiology and biotechnology , biochemistry , medicine , immunology , disease
The protein level of human hepatitis B virus ( HBV ) in infection is variable, depending on patient context. We previously reported that HBV X protein ( HB x) induces hepatic lipid accumulation and inflammation. Here, we show that abnormal levels of hepatic fatty acids increase HB x protein stability during HBV expression, resulting in the potentiation of HB x‐induced inflammation. Reactive oxygen species, Ca 2+ signaling and expression levels of various lipid metabolic genes were investigated in HB x‐expressing cells and in HB x transgenic mice. Fatty acids, including palmitate, stearate and oleate, increased HB x protein stability by preventing proteasome‐dependent degradation. Hepatic inflammation induced by a high fat diet ( HFD ) and HB x was measured based on the expression of interleukin–6 and tumor necrosis factor α. In addition, the protein level of HB x increased in HFD – HB x transgenic mice. Reactive oxygen species production and intracellular Ca 2+ signal activation play critical roles in fatty‐acid‐induced HB x stabilization. Abnormal levels of hepatic fatty acids resulted in synergistic induction of HB x protein and liver inflammatory gene expression through HB x protein stabilization. These results indicate that different fatty acid levels in the liver might affect HBV ‐induced pathogenesis.