Interferon alpha-inducible protein 6 (IFI6) and IFI27 may regulate the intensity of innate immune responses induced after viral infections in cell cultures and in vivo (Villamayor L, López-García D et al., 2023; Villamayor L, Rivero V et al., 2023; Rivero V et al., 2024). The molecular mechanism likely involves the interaction of IFI6 or IFI27 with dsRNAs and pattern recognition receptors such as DDX58 (RIG-I) and IFIH1 (MDA5), impairing the receptor activation by viral RNA (Villamayor L, López-García D et al., 2023; Villamayor L, Rivero V et al., 2023). In addition, some studies suggest that IFI6 and IFI27 modulate cellular responses, such as programmed cell death, to influence the balance between immune response and cellular damage caused by microbial infection or by health conditions associated with cancer (Gytz H et al., 2017; Wang H et al., 2018).
This Reactome event shows interaction between the outer mitochondrial membrane (OMM)-bound IFI6, IFI27 and cytosolic DDX58 (RIG-I) in the presence of viral RNA. However, IFI6 is primarily localized in the inner mitochondrial membrane (Cheriyath V et al., 2018; Liu Z et al., 2020). Further clarifications are needed for this interaction.
