The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling
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 cytokin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1176177/full |
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| author | Laura Villamayor Darío López-García Vanessa Rivero Luis Martínez-Sobrido Aitor Nogales Marta L. DeDiego |
| author_facet | Laura Villamayor Darío López-García Vanessa Rivero Luis Martínez-Sobrido Aitor Nogales Marta L. DeDiego |
| author_sort | Laura Villamayor |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:32:58Z |
| format | Article |
| id | doaj.art-119c2ee2587f4ecc8ad9ed9a98aa29f0 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-09T15:32:58Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-119c2ee2587f4ecc8ad9ed9a98aa29f02023-04-28T05:13:34ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-04-011410.3389/fmicb.2023.11761771176177The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signalingLaura Villamayor0Darío López-García1Vanessa Rivero2Luis Martínez-Sobrido3Aitor Nogales4Marta L. DeDiego5Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, SpainDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, SpainDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, SpainTexas Biomedical Research Institute, San Antonio, TX, United StatesCenter for Animal Health Research, CISA-INIA-CSIC, Madrid, SpainDepartment of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, SpainThe 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1176177/fullIFI27innate immune responsesinterferoninflammationinfluenzaSARS-CoV-2 |
| spellingShingle | Laura Villamayor Darío López-García Vanessa Rivero Luis Martínez-Sobrido Aitor Nogales Marta L. DeDiego The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling Frontiers in Microbiology IFI27 innate immune responses interferon inflammation influenza SARS-CoV-2 |
| title | The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling |
| title_full | The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling |
| title_fullStr | The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling |
| title_full_unstemmed | The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling |
| title_short | The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling |
| title_sort | ifn stimulated gene ifi27 counteracts innate immune responses after viral infections by interfering with rig i signaling |
| topic | IFI27 innate immune responses interferon inflammation influenza SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1176177/full |
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