Interaction between FMDV L and transcription factor ADNP is required for optimal viral replication.

The foot-and-mouth disease virus (FMDV) leader protease (L) inhibits host translation and transcription affecting the expression of several factors involved in innate immunity. In this study, we have identified the host transcription factor ADNP (activity dependent neuroprotective protein) as an L interacting protein by mass spectrometry. We show that L can bind to ADNP in vitro and in cell culture. RNAi of ADNP negatively affected virus replication and higher levels of interferon (IFN) and IFN-stimulated gene expression were detected. Importantly, infection with FMDV wild type but not with a virus lacking Lpro (leaderless), induced recruitment of ADNP to IFN-α promoter sites early during infection. Furthermore, we found that L and ADNP are in a protein complex with the ubiquitous chromatin remodeling factor Brg-1. Our results uncover a novel role of FMDV L in targeting ADNP and modulation of its transcription repressive function to decrease the expression of IFN and ISGs.