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Front Cell Infect Microbiol
. 2024 Oct 4:14:1470924.
doi: 10.3389/fcimb.2024.1470924. eCollection 2024. The IFN-induced protein IFI27 binds MDA5 and counteracts its activation after SARS-CoV-2 infection
Vanessa Rivero 1 , Julia Carrión-Cruz 1 , Darío López-García 1 , Marta L DeDiego 1
Affiliations
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; RIG-I-like receptors; SARS-CoV-2; inflammation; innate immune responses; innate immunity; interferon.
. 2024 Oct 4:14:1470924.
doi: 10.3389/fcimb.2024.1470924. eCollection 2024. The IFN-induced protein IFI27 binds MDA5 and counteracts its activation after SARS-CoV-2 infection
Vanessa Rivero 1 , Julia Carrión-Cruz 1 , Darío López-García 1 , Marta L DeDiego 1
Affiliations
- PMID: 39431052
- PMCID: PMC11486742
- DOI: 10.3389/fcimb.2024.1470924
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; RIG-I-like receptors; SARS-CoV-2; inflammation; innate immune responses; innate immunity; interferon.