野生型和突变型甲病毒感染小鼠成纤维细胞后α/β干扰素诱导的特征

Characteristics of alpha/beta interferon induction after infection of murine fibroblasts with wild-type and mutant alphaviruses.

作者信息

Burke Crystal W, Gardner Christina L, Steffan Joshua J, Ryman Kate D, Klimstra William B

机构信息

Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.

出版信息

Virology. 2009 Dec 5;395(1):121-32. doi: 10.1016/j.virol.2009.08.039. Epub 2009 Sep 25.

We examined the characteristics of interferon alpha/beta (IFN-alpha/beta) 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-alpha/beta. In contrast, infection of MEFs with multiple alphaviruses failed to elicit detectable IFN-alpha/beta. In more detailed studies, Sindbis virus (SINV) infection caused dimerization and nuclear migration of IRF3, but minimal IFN-beta 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 shutoff induced IFN-alpha/beta in the MEF cultures dependent upon the activities of the TBK1 IRF3 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 IRF3 activation but also may avoid detection by host PRRs early after infection.

我们检测了甲型病毒或对照仙台病毒（SeV）感染小鼠成纤维细胞（MEF）后干扰素α/β（IFN-α/β）诱导的特征。正如预期的那样，野生型（wt）MEF感染SeV导致IRF3强烈二聚化并产生高水平的IFN-α/β。相比之下，多种甲型病毒感染MEF未能引发可检测到的IFN-α/β。在更详细的研究中，辛德毕斯病毒（SINV）感染导致IRF3二聚化和核迁移，但IFN-β启动子活性极低，尽管令人惊讶的是，感染早期的细胞对其他刺激产生IFN的能力正常。一种在宿主大分子合成关闭方面有缺陷的SINV突变体在MEF培养物中诱导IFN-α/β，这依赖于TBK1 IRF3激活激酶以及宿主模式识别受体（PRR）PKR和MDA5的活性，但不依赖于RIG-I。这些结果表明，野生型甲型病毒在IRF3激活后拮抗IFN诱导，但也可能在感染早期避免被宿主PRR检测到。