Characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses.
Characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses.
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DOI：
10.1016/j.virol.2009.08.039
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发表时间：
2009-12-05
期刊：
影响因子：
3.7
通讯作者：
Klimstra, William B.
中科院分区：
文献类型：
--
作者：
Burke, Crystal W.;Gardner, Christina L.;Steffan, Joshua J.;Ryman, Kate D.;Klimstra, William B.
我们检测了α病毒和对照仙台病毒感染小鼠成纤维细胞后干扰素α/β(干扰素-α/β)的诱导特性。正如预期的那样，野生型MEF的SeV感染导致了IRF3的强烈二聚化和高水平的干扰素-α/β的产生。相比之下，感染多种甲型病毒的MEF未能诱导出可检测到的干扰素-α/β。在更详细的研究中，辛德比斯病毒感染引起了IRF3的二聚化和核迁移，但干扰素-β启动子活性很低，尽管令人惊讶的是，感染细胞在感染后早期就能通过其他刺激产生干扰素。宿主大分子合成缺陷的SINV突变体在MEF培养中诱导的干扰素-α/β依赖于TBK1IRF-3激活激酶和宿主模式识别受体(PRR)PKR和MDA5的活性，而不是RIG-I。这些结果表明，野生型甲型病毒在IRF-3激活后拮抗干扰素的诱导，但也可能在感染后早期避开宿主PRRs的检测。
We examined the characteristics of interferon alpha/beta (IFN-α/β) induction after alphavirus or control Sendai virus (SeV) infection of murine fibroblasts (MEFs). As expected, SeV infection of wild-type (wt) MEFs resulted in strong dimerization of IRF3 and the production of high levels of IFN-α/β. In contrast, infection of MEFs with multiple alphaviruses failed to elicit detectable IFN-α/β. In more detailed studies, Sindbis virus (SINV) infection caused dimerization and nuclear migration of IRF3, but minimal IFN-β promoter activity although surprisingly, the infected cells were competent for IFN production by other stimuli early after infection. A SINV mutant defective in host macromolecular synthesis shut-off induced IFN-α/β in the MEF cultures dependent upon the activities of the TBK1 IRF-3 activating kinase and host pattern recognition receptors (PRRs) PKR and MDA5 but not RIG-I. These results suggest that wild type alphaviruses antagonize IFN induction after IRF-3 activation but also may avoid detection by host PRRs early after infection.
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DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
影响因子：
6.2
作者：
Carpentier, Pamela A.;Williams, Bryan R.;Miller, Stephen D.
通讯作者：
Miller, Stephen D.
影响因子：
5.4
作者：
Gilfoy, Felicia D.;Mason, Peter W.
通讯作者：
Mason, Peter W.
影响因子：
5.4
作者：
Garmashova, Natalia;Gorchakov, Rodion;Frolov, Ilya
通讯作者：
Frolov, Ilya
影响因子：
3.7
作者：
Gardner, Christina L.;Yin, Jun;Burke, Crystal W.;Klimstra, William B.;Ryman, Kate D.
通讯作者：
Ryman, Kate D.