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

Autor:	Rivero V; Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain., Carrión-Cruz J; Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain., López-García D; Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain., DeDiego ML; Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2024 Oct 04; Vol. 14, pp. 1470924. Date of Electronic Publication: 2024 Oct 04 (Print Publication: 2024).
DOI:	10.3389/fcimb.2024.1470924
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Rivero, Carrión-Cruz, López-García and DeDiego.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu