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

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Foot-and-mouth disease virus (FMDV) leader protease (Lpro) suppresses host innate immunity.
• Understanding host-pathogen interactions is key to controlling viral infections.

Purpose of the Study:

• Identify host factors interacting with FMDV Lpro.
• Elucidate the role of ADNP in FMDV infection and innate immune modulation.

Main Methods:

• Mass spectrometry to identify Lpro interacting proteins.
• In vitro and cell culture assays to confirm Lpro-ADNP binding.
• RNA interference (RNAi) to assess ADNP's role in viral replication.
• Chromatin immunoprecipitation (ChIP) to study protein recruitment to promoters.

Main Results:

• ADNP identified as an Lpro interacting protein.
• Lpro binds ADNP, and ADNP depletion reduces FMDV replication and increases interferon (IFN) and IFN-stimulated gene (ISG) expression.
• FMDV infection recruits ADNP to IFN-α promoter sites.
• Lpro and ADNP form a complex with Brg-1, a chromatin remodeling factor.

Conclusions:

• FMDV Lpro targets ADNP to suppress IFN and ISG expression.
• Lpro modulates ADNP's transcription repressive function, contributing to viral immune evasion.
• This study reveals a novel mechanism of viral immune suppression involving ADNP and Brg-1.