中科院微生物所劉文軍課題組近期研究發(fā)現(xiàn),，宿主細(xì)胞因子CypA能夠與流感病毒的M1蛋白相互作用并抑制流感病毒的早期復(fù)制。該研究結(jié)果發(fā)表在Cellular Microbiology雜志上,。
研究病毒與宿主的相互作用,，對于深入了解病毒的致病機(jī)理從而尋找合適的抗病毒方案具有非常重要的理論意義和實(shí)際應(yīng)用價值。禽流感病毒的M1蛋白是流感病毒粒子中含量最豐富也是相對比較保守的蛋白,，它在流感病毒的復(fù)制過程中起著非常重要的作用,。宿主細(xì)胞因子CypA是擁有肽基脯氨酸順反異構(gòu)酶活性的多功能蛋白家族的一員，它參與多種病毒的復(fù)制,，如HIV-1,VSV, VV, HCV等,。
劉文軍課題組的研究結(jié)果表明，宿主蛋白CypA能夠在病毒復(fù)制過程中整合到流感病毒粒子中,，作為一種限制性因子與流感病毒的M1蛋白發(fā)生相互作用,，阻礙M1蛋白從細(xì)胞質(zhì)輸入到細(xì)胞核中,，從而起到抑制病毒復(fù)制的作用。進(jìn)一步的研究還表明,，CypA在細(xì)胞中的表達(dá)水平升高會降低細(xì)胞的易染性,。因此，CypA是流感病毒的一種抑制性因子,。該研究為闡明流感病毒跨種間傳播的分子機(jī)制及抗流感病毒藥物設(shè)計奠定了理論基礎(chǔ),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
