期刊论文详细信息
Frontiers in Microbiology
The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling
Microbiology
Aitor Nogales1  Laura Villamayor2  Darío López-García2  Marta L. DeDiego2  Vanessa Rivero2  Luis Martínez-Sobrido3 
[1] Center for Animal Health Research, CISA-INIA-CSIC, Madrid, Spain;Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain;Texas Biomedical Research Institute, San Antonio, TX, United States;
关键词: IFI27;    innate immune responses;    interferon;    inflammation;    influenza;    SARS-CoV-2;    virus-host interactions;   
DOI  :  10.3389/fmicb.2023.1176177
 received in 2023-02-28, accepted in 2023-04-13,  发布年份 2023
来源: Frontiers
PDF
【 摘 要 】

The recognition of viral nucleic acids by host pattern recognition receptors (PRRs) is critical for initiating innate immune responses against viral infections. These innate immune responses are mediated by the induction of interferons (IFNs), IFN-stimulated genes (ISGs) and pro-inflammatory cytokines. However, regulatory mechanisms are critical to avoid excessive or long-lasting innate immune responses that may cause detrimental hyperinflammation. Here, we identified a novel regulatory function of the ISG, IFN alpha inducible protein 27 (IFI27) in counteracting the innate immune responses triggered by cytoplasmic RNA recognition and binding. Our model systems included three unrelated viral infections caused by Influenza A virus (IAV), Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), and Sendai virus (SeV), and transfection with an analog of double-stranded (ds) RNA. Furthermore, we found that IFI27 has a positive effect on IAV and SARS-CoV-2 replication, most likely due to its ability to counteract host-induced antiviral responses, including in vivo. We also show that IFI27 interacts with nucleic acids and PRR retinoic acid-inducible gene I (RIG-I), being the interaction of IFI27 with RIG-I most likely mediated through RNA binding. Interestingly, our results indicate that interaction of IFI27 with RIG-I impairs RIG-I activation, providing a molecular mechanism for the effect of IFI27 on modulating innate immune responses. Our study identifies a molecular mechanism that may explain the effect of IFI27 in counterbalancing innate immune responses to RNA viral infections and preventing excessive innate immune responses. Therefore, this study will have important implications in drug design to control viral infections and viral-induced pathology.

【 授权许可】

Unknown   
Copyright © 2023 Villamayor, López-García, Rivero, Martínez-Sobrido, Nogales and DeDiego.

【 预 览 】
附件列表
Files Size Format View
RO202310109317187ZK.pdf 10301KB PDF download
  文献评价指标  
  下载次数:9次 浏览次数:0次