RIOK3 and Its Alternatively Spliced Isoform Have Disparate Roles in the Innate Immune Response to Rift Valley Fever Virus (MP12) Infection.
RIOK3 and Its Alternatively Spliced Isoform Have Disparate Roles in the Innate Immune Response to Rift Valley Fever Virus (MP12) Infection.
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DOI：
10.3390/v14092064
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发表时间：
2022-09-17
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;White LA;Lanchy JM;Lodmell JS
裂谷热病毒（RVFV）是一种致病性人类和牲畜RNA病毒，对公共卫生和生物安全构成重大威胁。在RVFV感染期间，非典型激酶RIOK3在先天免疫应答中起重要作用。尽管其在先天免疫中的确切功能尚未完全了解，但RIOK3已被证明是在上皮细胞中对RVFV产生抗病毒干扰素（IFN）应答所必需的。此外，免疫刺激后RIOK3 mRNA的剪接模式发生了显著变化，RIOK3的优势剪接异构体RIOK3 X2对IFN的应答具有相反的抑制作用。我们发现，虽然RIOK3是重要的负调控这一炎症途径，其选择性剪接亚型，RIOK3 X2，刺激it.Overall，这些数据表明，RIOK3和X2亚型有独特的作用，在单独的先天免疫途径，响应RVFV感染。
Rift Valley fever virus (RVFV) is a pathogenic human and livestock RNA virus that poses a significant threat to public health and biosecurity. During RVFV infection, the atypical kinase RIOK3 plays important roles in the innate immune response. Although its exact functions in innate immunity are not completely understood, RIOK3 has been shown to be necessary for mounting an antiviral interferon (IFN) response to RVFV in epithelial cells. Furthermore, after immune stimulation, the splicing pattern for RIOK3 mRNA changes markedly, and RIOK3′s dominant alternatively spliced isoform, RIOK3 X2, exhibits an opposite effect on the IFN response by dampening it. Here, we further investigate the roles of RIOK3 and its spliced isoform in other innate immune responses to RVFV, namely the NFκB-mediated inflammatory response. We find that while RIOK3 is important for negatively regulating this inflammatory pathway, its alternatively spliced isoform, RIOK3 X2, stimulates it. Overall, these data demonstrate that both RIOK3 and its X2 isoform have unique roles in separate innate immune pathways that respond to RVFV infection.
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