Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3.
Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3.
复制标题
DOI：
10.1038/srep06006
复制
发表时间：
2014-08-08
影响因子：
4.6
通讯作者：
Nishida N
中科院分区：
文献类型：
--
作者：
Homma T;Ishibashi D;Nakagaki T;Fuse T;Sano K;Satoh K;Atarashi R;Nishida N
作为对各种病毒入侵的快速反应，干扰素调节因子-3(IRF-3)最初被磷酸化激活，并在大多数细胞类型中主要上调I型干扰素(IFN-I)。我们先前报道，依赖于IRF-3的宿主先天免疫反应部分干扰了Pron的感染。在这里，我们发现稳定的Pron感染抑制了IRF-3基因的表达。病毒感染细胞经抗病毒药物处理后，IRF-3基因启动子活性下降的现象明显恢复，提示病毒感染直接影响IRF-3转录调控。我们利用荧光素酶报告系统进一步研究了小鼠IRF-3 5‘-侧翼区的启动子活性，发现-119到-1核苷酸是启动子活性所必需的。在这个区域内，Oct-1结合位点的突变显著降低了启动子的活性，染色质免疫沉淀(ChIP)实验表明Oct-1确实与该区域结合。此外，OCT-1的过表达增加了IRF-3的启动子活性。有趣的是，与未感染组相比，感染普恩病毒的细胞和小鼠大脑中的Oct-1蛋白显著减少。综上所述，我们得出结论：Pron感染可以干扰Oct-1的功能，导致IRF-3的下调。
As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3.
登录
查看更多内容
影响因子：
64.8
作者：
Moreno, Julie A.;Radford, Helois;Peretti, Diego;Steinert, Joern R.;Verity, Nicholas;Martin, Maria Guerra;Halliday, Mark;Morgan, Jason;Dinsdale, David;Ortori, Catherine A.;Barrett, David A.;Tsaytler, Pavel;Bertolotti, Anne;Willis, Anne E.;Bushell, Martin;Mallucci, Giovanna R.
通讯作者：
Mallucci, Giovanna R.
对prion感染的独立于MyD88的先天免疫反应的保护作用。
影响因子：
2.3
作者：
Ishibashi D;Atarashi R;Nishida N
通讯作者：
Nishida N
影响因子：
5.4
作者：
Doehle, Brian P.;Hladik, Florian;Gale, Michael, Jr.
通讯作者：
Gale, Michael, Jr.
影响因子：
3.1
作者：
Lowther, WJ;Moore, PA;Pitha, PM
通讯作者：
Pitha, PM
影响因子：
9.9
作者：
Hwang, Daehee;Lee, Inyoul Y.;Yoo, Hyuntae;Gehlenborg, Nils;Cho, Ji-Hoon;Petritis, Brianne;Baxter, David;Pitstick, Rose;Young, Rebecca;Spicer, Doug;Price, Nathan D.;Hohmann, John G.;DeArmond, Stephen J.;Carlson, George A.;Hood, Leroy E.
通讯作者：
Hood, Leroy E.