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

Gisselle N Medina1, Giselle M Knudsen2, Alexander L Greninger3

  • 1Plum Island Animal Disease Center (PIADC), North Atlantic Area, Agricultural Research Service US Department of Agriculture, Greenport, NY 11944, USA.

Virology
|February 21, 2017
PubMed

Insights

The foot-and-mouth disease virus leader protease (Lpro) targets the ADNP protein, reducing innate immune responses. This interaction is crucial for viral replication and immune evasion strategies.

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.
Keywords:
ADNPBrg1Chromatin remodelingFMDVIFNInnate immunityL(pro)LeaderRepressorTranscription

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