程序性细胞死亡因子10抑制Ⅰ型干扰素表达并促进FMDV复制

Programmed Cell Death Factor 10 Inhibits TypeⅠInterferon Expression and Promotes the Replication of Foot-and-mouth Disease Virus

旨在探究宿主蛋白程序性细胞死亡因子10(programmed cell death factor 10,PDCD10)通过抑制Ⅰ型干扰素表达进而促进口蹄疫病毒(foot-and-mouth disease virus,FMDV)的复制。首先,本研究验证了过表达和沉默PDCD10对FMDV复制的影响,接着利用双荧光素酶报告系统探究PDCD10对Ⅰ型干扰素信号通路活化的影响,最后,利用实时荧光定量PCR探究PDCD10对Ⅰ型干扰素通路下游刺激基因(IFN-stimulated genes,ISGs)转录的影响。结果表明,过表达PDCD10显著促进FMDV的复制,沉默PDCD10显著抑制FMDV的复制。与对照相比,过表达PDCD10后感染仙台病毒(Sendai virus,SeV)的细胞培养液上清液显著促进FMDV复制,进一步,PDCD10显著抑制SeV诱导的IFN-β启动子以及NF-κB的激活且呈剂量依赖性,并且PDCD10负调控Ⅰ型干扰素通路信号分子转录,最后还发现PDCD10负调控Ⅰ型干扰素下游ISGs转录。本研究结果为深入探究PDCD10在抗病毒天然免疫中的作用积累了资料。

The purpose of this study is to explore how the host protein programmed cell death factor 10(PDCD10)can inhibit the expression of typeⅠinterferon to promote the replication of foot-and-mouth disease virus(FMDV).First,this study verified the effect of overexpression and silencing of PDCD10 on FMDV replication.Secondly,the dual-luciferase reporter system was used to explore the effect of PDCD10 on the activation of typeⅠinterferon signaling pathway.Finally,real-time fluorescent quantitative PCR was used to explore the effect of PDCD10 on the transcription of stimulating genes downstream of the typeⅠinterferon pathway.The results showed that overexpression of PDCD10 significantly promoted FMDV replication while silencing PDCD10 significantly inhibited FMDV replication.Compared with the control,the cell culture supernatant infected with Sendai virus(SeV)after overexpression of PDCD10 significantly promoted FMDV replication.Furthermore,PDCD10 significantly inhibited the activation of IFN-βpromoter and NF-κB induced by SeV in a dose-dependent manner,and PDCD10 negatively regulated the transcription of typeⅠinterferon pathway signal molecules.Finally,it was found that PDCD10 negatively regulated the transcription of ISGs downstream of typeⅠinterferon.The results of this study have accumulated data for the in-depth exploration of the role of PDCD10 in antiviral innate immunity.