Mallard ILF2 negatively regulates type I IFN production through autophagy-lysosome-dependent degradation of IRF7.

Abstract

Interleukin enhancer-binding factor 2 (ILF2) has been reported to act as either a positive or negative regulator of viral infection by directly affecting viral RNA replication. In this study, mallard ILF2 was found to impair type I IFN production, thereby facilitating the replication of duck Tembusu virus (DTMUV). The overexpression of ILF2 in duck embryo fibroblast (DEF) cells resulted in suppression of polyI: C- and DTMUV-induced production of three type I interferons (IFNs), IFN-α, IFN-β, IFN-κ-like, whereas the knockdown of ILF2 expression in DEF cells enhanced type I IFN production and inhibited DTMUV infection. It is also found that the zinc finger-related domain (DZF) of ILF2 interacts with the IRF association domain (IAD) of IRF7, and ILF2 may cause autophagic degradation of IRF7 at the protein level. Furthermore, ILF2 was found to interact also with Beclin1, and Beclin1 is necessary for ILF2-induced IRF7 degradation as ILF2-induced IRF7 degradation was significantly restored after knockdown of Beclin1. These results provide obvious evidence that ILF2 recruits Beclin1 to degrade IRF7, resulting in the suppression of type I IFN production in DEF cells.