Alternative Splicing of RIOK3 Engages the Noncanonical NFκB Pathway during Rift Valley Fever Virus Infection.
Alternative Splicing of RIOK3 Engages the Noncanonical NFκB Pathway during Rift Valley Fever Virus Infection.
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DOI：
10.3390/v15071566
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发表时间：
2023-07-18
期刊：
影响因子：
--
通讯作者：
Lodmell JS
中科院分区：
文献类型：
--
作者：
Bisom TC;Smelser H;Lanchy JM;Lodmell JS
虽然非典型的NFκB通路最初被认为是促进淋巴器官发生的细胞通路，但在过去的20年里，它在先天免疫中的作用已经得到了更多的认识。特别是，非典型的NFκB通路已被发现在感染期间被一些RNA病毒激活甚至利用。有趣的是，这一途径的激活已被证明在破坏1型干扰素（IFN）的转录中起作用，这就解释了为什么这种反应可以被一些病毒所利用。裂谷热病毒（RVFV）是一种三节段双义RNA病毒，对家畜和人类健康构成相当大的威胁。在此之前，我们发现非典型激酶RIOK3对人类上皮细胞感染RVFV时产生IFN反应很重要，并且在感染RVFV （MP12菌株）后不久，RIOK3 mRNA被选择性地拼接到其X2亚型上，该亚型编码截断的RIOK3蛋白。RIOK3 mRNA的选择性剪接对IFN反应有抑制作用，但也刺激nfκ b介导的炎症反应。在这里，我们证明了RIOK3 mRNA的选择性剪接与非典型NFκB通路的激活有关，并表明RVFV （MP12）选择了这一途径来增强病毒在感染期间的成功。
Although the noncanonical NFκB pathway was originally identified as a cellular pathway contributing to lymphoid organogenesis, in the past 20 years, its involvement in innate immunity has become more appreciated. In particular, the noncanonical NFκB pathway has been found to be activated and even exploited by some RNA viruses during infection. Intriguingly, activation of this pathway has been shown to have a role in disrupting transcription of type 1 interferon (IFN), suggesting a rationale for why this response could be co-opted by some viruses. Rift Valley fever virus (RVFV) is a trisegmented ambisense RNA virus that poses a considerable threat to domestic livestock and human health. Previously, we showed the atypical kinase RIOK3 is important for mounting an IFN response to RVFV infection of human epithelial cells, and shortly following infection with RVFV (MP12 strain), RIOK3 mRNA is alternatively spliced to its X2 isoform that encodes a truncated RIOK3 protein. Alternative splicing of RIOK3 mRNA has an inhibitory effect on the IFN response but also stimulates an NFκB-mediated inflammatory response. Here, we demonstrate alternative splicing of RIOK3 mRNA is associated with activation of the noncanonical NFκB pathway and suggest this pathway is co-opted by RVFV (MP12) to enhance viral success during infection.
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DOI：
10.3390/v14092064
发表时间：
2022-09-17
期刊：
Viruses
影响因子：
--
作者：
Bisom TC;White LA;Lanchy JM;Lodmell JS
通讯作者：
Lodmell JS
影响因子：
32.4
作者：
Dejardin, E;Droin, NM;Green, DR
通讯作者：
Green, DR
影响因子：
5.4
作者：
Billecocq, A;Spiegel, M;Haller, O
通讯作者：
Haller, O
影响因子：
64.5
作者：
BAEUERLE, PA;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
2.7
作者：
Adams, Michael J.;Lefkowitz, Elliot J.;Davison, Andrew J.
通讯作者：
Davison, Andrew J.