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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1470924

The IFN-induced protein IFI27 binds MDA5 and counteracts its activation after SARS-CoV-2 infection

Provisionally accepted
Vanessa Rivero Vanessa Rivero Julia Carrion-Cruz Julia Carrion-Cruz Darío López-García Darío López-García Marta L. De Diego Marta L. De Diego *
  • National Center for Biotechnology, Spanish National Research Council (CSIC), Madrid, Spain

The final, formatted version of the article will be published soon.

    Innate immune responses are induced after viral infections, being these responses essential to establish an antiviral response in the host. The RIG-I-like receptors (RLRs), RIG-I and MDA5 are pivotal for virus detection by recognizing viral RNAs in the cytoplasm of infected cells, initiating these responses. However, since excessive responses can have a negative effect on the host, regulatory feedback mechanisms are needed. In this work, we describe that IFN alpha-inducible protein 27 (IFI27) co-immunoprecipitates with melanoma differentiation-associated protein 5 (MDA5), being this interaction likely mediated by RNAs.In addition, by using IFI27 overexpression, knock-out, and knock-down cells, we show that IFI27 inhibits MDA5 oligomerization and activation, counteracting the innate immune responses induced after SARS-CoV-2 infections or after polyinosinic-polycytidylic acid (poly(I:C)) transfection. Furthermore, our data indicate that IFI27 competes with MDA5 for poly(I:C) binding, providing a likely explanation for the effect of IFI27 in inhibiting MDA5 activation. This new function of IFI27 could be used to design target-driven compounds to treat diseases associated with an exacerbated induction of innate immune responses, such as those induced by SARS-CoV-2.

    Keywords: IFI27, MDA5, Innate immune responses, interferon, Inflammation, SARS-CoV-2, innate immunity, RIG-I-like receptors

    Received: 26 Jul 2024; Accepted: 06 Sep 2024.

    Copyright: © 2024 Rivero, Carrion-Cruz, López-García and L. De Diego. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Marta L. De Diego, National Center for Biotechnology, Spanish National Research Council (CSIC), Madrid, Spain

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