The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling
Year: 2023
Type: article
Abstract: 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.
Source: Frontiers in Microbiology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,295
Funders: Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades, European Commission, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, Consejo Superior de Investigaciones Científicas, Agencia Estatal de Investigación, National Institute of Allergy and Infectious Diseases, Centro Nacional de Biotecnología, NextGenerationEU
Awards: G1044684712, G1105844351, G1175115578, G1255325603, G1455481585, G210041235, G2262748287, G2365329623, G2390397592, G2551911579, G2601397997, G2745972340, G2795468041, G2840684682, G2968944366, G300979063, G34346518, G3480869486, G3681454997, G4042783231, G425668148, Dynamics of the protective vaccine-induced human influenza neuraminidase B cell response, G488842982, G491712853, G5080475149, G5099673792, G5132640529, G5195188938, G5404395142, G586857820, G624877701, G6326031618, G6526903474, The origin and future protective activity of SARS-CoV-2 RBD specific neutralizing antibodies, G7084143925, G7685134749, G7731791180, G7805626310, G7811397228, G7863371703, G8497050386, G8764595522
OpenAlex ID: W4367320271