ANXA1促进Ⅰ型干扰素表达抑制口蹄疫病毒的复制

Annexin-1 promotes type I interferon production and inhibits foot-and-mouth disease virus replication

摘要:

[目的]研究膜联蛋白A1（Annexin A1，ANXA1）对I型干扰素（I-IFN）表达及口蹄疫病毒（FMDV）复制的影响。[方法]开展过表达及Knockdown实验，检测ANXA1对FMDV复制的影响。利用双荧光素酶报告系统检测ANXA1对ISRE和IFN-β启动子元件活化的影响。双荧光素酶报告系统鉴定ANXA1调控I-IFN通路活化靶分子。Western blotting检测ANXA1对干扰素调解因子3（IRF3）磷酸化的影响。Real-time PCR检测ANXA1对干扰素刺激基因（ISGs）的影响。[结果]过表达ANXA1显著抑制FMDV的复制；下调ANXA1表达促进FMDV复制（P<0.01或P<0.05）；ANXA1促I型干扰素通路活化，呈现剂量依赖性（P<0.01）。ANXA1显著增强IRF3的磷酸化，促进ISGs的表达（P<0.01或P<0.05）。[结论]ANXA1促进I-IFN表达，抑制FMDV的复制。

Abstract:

[Objective] We studied the regulatory effect of Annexin-1(ANXA1) on type I interferon (I-IFN) production and foot-and-mouth disease virus (FMDV) replication.[Methods] We used overexpression and knockdown assays to determine the role of ANXA1 in FMDV-infected cells.Then we evaluated the influence of ANXA1 on ISRE and IFN-β promoter activation by dual luciferase reporter assays.To confirm the regulatory role of ANXA1 on type I IFN pathway,IFN regulatory factor 3(IRF3) phosphorylation was detected by Western blotting.Expression of interferon-stimulated genes (ISGs) was measured by RT-PCR to investigate the effect of ANXA1 on ISGs expression.[Results] Overexpression of ANXA1 significantly suppressed FMDV replication and knockdown of ANXA1 expression enhanced virus replication,showing an antiviral role of ANXA1 in FMDV-infected cells (P<0.01 or P<0.05).ANXA1 promoted the activation of type I IFN pathway in a dose-dependent manner.Overexpression of ANXA1 enhanced IRF3 phosphorylation and ISGs expression (P<0.01 or P<0.05).[Conclusion] ANXA1 enhances type I IFN production and suppresses FMDV replication.