Regulation of STAT signaling in mouse bone marrow derived dendritic cells by respiratory syncytial virus.
Regulation of STAT signaling in mouse bone marrow derived dendritic cells by respiratory syncytial virus.
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通过呼吸合胞病毒衍生的小鼠骨髓中Stat信号的调节。
DOI：
10.1016/j.virusres.2011.01.007
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发表时间：
2011-03
期刊：
影响因子：
5
通讯作者：
Harrod, Kevin S.
中科院分区：
文献类型：
--
作者：
Jie, Zhijun;Dinwiddie, Darrell L.;Senft, Albert P.;Harrod, Kevin S.
关键词：
树突状细胞（dc）作为病毒入侵的门户，以及参与抗病毒宿主反应的强效抗原呈递细胞（APCs）。干扰素（ifn）是在细菌和病毒感染的反应中产生的，并激活先天免疫反应，有效地抵消和清除致病入侵者。呼吸道合胞病毒（RSV）可抑制ifn介导的上皮细胞信号通路；然而，RSV对树突状细胞（dc）中IFN信号的影响尚不清楚。采用不同感染倍数（MOI）对小鼠骨髓源性dc （bmdc）进行模拟或感染RSV 24 h，然后用干扰素-β (IFN-β)、IFN-γ或白细胞介素-10 （IL-10）等不同细胞因子处理。RT-PCR检测RSV非结构蛋白-1 （NS-1）和NS-2的mRNA表达。免疫印迹法检测Janus家族激酶信号转导和转录激活因子（JAK/STAT）信号蛋白的表达。免疫荧光法测定特异性信号蛋白的核定位。感染RSV后，随着MOI的增加，BMDCs中NS-1或NS-2 mRNA的表达量增加，表明BMDCs允许病毒基因表达。对IFN-β信号级联的进一步研究表明，RSV感染增加了BMDCs中STAT1和STAT2的细胞总水平，但破坏了IFN-β依赖性的STAT1和STAT2的磷酸化和核定位。RSV对STAT1和STAT2磷酸化和易位的抑制作用通过UV灭活被消除。相反，RSV不抑制IFN-γ刺激的STAT1磷酸化和核定位。il -10刺激的STAT3磷酸化也不受RSV的影响。除了RSV在上皮细胞中通过降解机制抑制STAT蛋白水平外，这些发现表明RSV还可以通过调节STAT1和STAT2磷酸化和核易位特异性抑制BMDCs中的I型干扰素反应。
Dendritic cells (DCs) act as a portal for virus invasion as well as potent antigen-presenting cells (APCs) involved in the antiviral host response. Interferons (IFNs) are produced in response to bacterial and viral infection and activate innate immune responses to efficiently counteract and remove pathogenic invaders. Respiratory syncytial virus (RSV) could inhibit IFN-mediated signaling pathway in epithelial cells; however, the effects of RSV on IFN signaling in the dendritic cells (DCs) are still unknown. Mouse bone marrow derived DCs (BMDCs) were mock or infected with RSV at different multiplicity of infection (MOI) for 24 h, and then treated with different cytokines such as interferon-β (IFN-β), IFN-γ or interleukin-10 (IL-10). The mRNA expression of RSV nonstructural protein-1 (NS-1) and NS-2 was detected by RT-PCR. The expression of Janus family kinase-signal transducer and activator of transcription (JAK/STAT) signaling proteins was assessed by immunoblotting assays. The nuclear localization of specific signaling proteins was determined by immunofluorescence assay. Increasing amounts of NS-1 or NS-2 mRNA expression in BMDCs were observed with infected RSV at increasing MOI, suggesting BMDCs were permissive for viral gene expression. Further examination of the IFN-β signaling cascade showed RSV infection increased the total cellular levels of STAT1 and STAT2 in BMDCs, but impaired the IFN-β-dependent phosphorylation and nuclear localization of STAT1 and STAT2. The inhibitory effects of RSV on STAT1 and STAT2 phosphorylation and translocation were abolished by UV inactivation. In contrast, RSV did not inhibit the IFN-γ-stimulated STAT1 phosphorylation and nuclear localization. IL-10-stimulated STAT3 phosphorylation was also unaffected by RSV. As well as RSV inhibiting STAT protein levels through degradation mechanisms in epithelial cells, these findings demonstrate that RSV also can specifically inhibit the type I interferon response in BMDCs through regulation of STAT1 and STAT2 phosphorylation and nuclear translocation.
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DOI：
10.1165/rcmb.2008-0229oc
发表时间：
2010-04-01
影响因子：
6.4
作者：
Senft, Albert P.;Taylor, Reed H.;Harrod, Kevin S.
通讯作者：
Harrod, Kevin S.
猿猴病毒 5 的 V 蛋白通过靶向 STAT1 进行蛋白酶体介导的降解来抑制干扰素信号传导
影响因子：
5.4
作者：
Didcock, L;Young, DF;Randall, RE
通讯作者：
Randall, RE
影响因子：
3.7
作者：
Parisien, JP;Lau, JF;Horvath, CM
通讯作者：
Horvath, CM
影响因子：
5.4
作者：
Rodriguez, JJ;Parisien, JP;Horvath, CM
通讯作者：
Horvath, CM
DOI：
10.1165/rcmb.2007-0285oc
发表时间：
2008-06-01
影响因子：
6.4
作者：
Dinwiddie, Darrell L.;Harrod, Kevin S.
通讯作者：
Harrod, Kevin S.