[转移贴]复旦发了一篇JV:关于HBV SHBs与cyclophilin A的相互作用及其意义

cao1976

原贴由yaoming发表于 2010-1-26 23:45


大陆在HBV领域以前一发表过5篇JV，
复旦大学医学院分子病毒学重点实验室最近又发了一篇：

标题：Hepatitis B surface antigen interacts and promotes cyclophilin A secretion: possible link to pathogenesis of HBV infection

作者：Xiaochen Tian, Chao Zhao, Hongguang Zhu, Weimin She, Jiming Zhang, Jing Liu, Lanjuan Li, Shusen Zheng, Yu-Mei Wen, and Youhua Xie

摘要：Cyclophilin A (CypA), predominantly located intracellularly, is a multi-functional protein. We previously reported decreased CypA levels in hepatocytes of transgenic mice expressing hepatitis B virus (HBV) surface antigen (HBsAg). In this study, we found that expression of HBV small surface protein (SHBs) in human hepatoma cell lines specifically triggered CypA secretion, while SHBs added extracellularly to culture medium did not. Moreover, CypA secretion was not promoted by the expression of a secretion deficient SHBs mutant, suggesting a close association between secretion of CypA and SHBs. Interaction between CypA and SHBs was observed using co-immunoprecipitation and GST pull-down assays. Hydrodynamic injection of the SHBs expression construct into C57BL/6J mice resulted in increased serum CypA levels and ALT/AST levels as well as the infiltration of inflammatory cells surrounding SHBs-positive hepatocytes. The inflammatory response and serum ALT/AST level were reduced when the chemotactic effect of CypA was inhibited by cyclosporine A (CsA) and anti-CD147 antibody. Furthermore, higher serum CypA levels were detected in chronic hepatitis B patients than healthy individuals. In HBV patients who had received liver transplatation, serum CypA levels declined dramatically following the loss of HBsAg as a consequence of liver transplantation. Taken together, these results indicate that expression and secretion of SHBs can promote CypA secretion, which may contribute to the pathogenesis of HBV infection.

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