中科院微生物所刘文军课题组近期研究发现，宿主细胞因子CypA能够与流感病毒的M1蛋白相互作用并抑制流感病毒的早期复制。该研究结果发表在Cellular Microbiology杂志上。
研究病毒与宿主的相互作用，对于深入了解病毒的致病机理从而寻找合适的抗病毒方案具有非常重要的理论意义和实际应用价值。禽流感病毒的M1蛋白是流感病毒粒子中含量最丰富也是相对比较保守的蛋白，它在流感病毒的复制过程中起着非常重要的作用。宿主细胞因子CypA是拥有肽基脯氨酸顺反异构酶活性的多功能蛋白家族的一员，它参与多种病毒的复制，如HIV-1,VSV, VV, HCV等。
刘文军课题组的研究结果表明，宿主蛋白CypA能够在病毒复制过程中整合到流感病毒粒子中，作为一种限制性因子与流感病毒的M1蛋白发生相互作用，阻碍M1蛋白从细胞质输入到细胞核中，从而起到抑制病毒复制的作用。进一步的研究还表明，CypA在细胞中的表达水平升高会降低细胞的易染性。因此，CypA是流感病毒的一种抑制性因子。该研究为阐明流感病毒跨种间传播的分子机制及抗流感病毒药物设计奠定了理论基础。（生物谷Bioon.com）
生物谷推荐原始出处：
Cellular Microbiology Volume 11 Issue 5, Pages 730 - 741 DOI：10.1111/j.1462-5822.2009.01286.x
Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication
Xiaoling Liu, 1,2 Lei Sun, 1 Maorong Yu, 1,2 Zengfu Wang, 1,2 Chongfeng Xu, 1,2 Qinghua Xue, 1,2 Ke Zhang, 1,2 Xin Ye, 3 Yoshihiro Kitamura 4 and Wenjun Liu 1,2,4 *
1 Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
2 Graduate University of Chinese Academy of Sciences, Beijing 100101, China.
3 Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
4 China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
ABSTRACT
Influenza A virus matrix protein (M1) is the most abundant conservative protein that regulates the replication, assembly and budding of the viral particles upon infection. Several host cell factors have been determined to interact with M1 possibly in regulating influenza virus replication. By yeast two-hybrid screening, the isomerase cyclophilin A (CypA) was identified to interact with the M1 protein. CypA specifically interacted with M1 both in vitro and in vivo. The mutagenesis results showed CypA bound to the functional middle (M) domain of M1. The depletion of endogenous CypA by RNA interference resulted in the increase of influenza virus infectivity while overexpression of CypA caused decreasing the infectivity in affected cells. The immunofluorescence assays indicated that overexpressed CypA deduced the infectivity and inhibited the translocation of M1 protein into the nucleus while did not affect nucleoprotein entering the nucleus. Further studies indicated that overexpression of CypA significantly increased M1 self-association. Western blot with purified virions confirmed that CypA was encapsidated within the virus particle. These results together indicated that CypA interacted with the M1 protein and affected the early stage of the viral replication.
