title: Interaction between FMDV Lproand transcription factor ADNP is required for optimal viral replication.
abstract: The foot-and-mouth disease virus (FMDV) leader protease (Lpro) 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 Lprointeracting protein by mass spectrometry. We show that Lprocan 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 Lproand ADNP are in a protein complex with the ubiquitous chromatin remodeling factor Brg-1. Our results uncover a novel role of FMDV Lproin targeting ADNP and modulation of its transcription repressive function to decrease the expression of IFN and ISGs.
authors.affiliation: Plum Island Animal Disease Center (PIADC), North Atlantic Area, Agricultural Research Service US Department of Agriculture, Greenport, NY 11944, USA.
authors.forename: Gisselle N
authors.initials: GN
authors.lastname: Medina
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA.
authors.forename: Giselle M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Howard Hughes Medical Institute and the Department of Biochemistry & Biophysics, University of California, San Francisco, CA 94158, USA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Greninger
authors.affiliation: Plum Island Animal Disease Center (PIADC), North Atlantic Area, Agricultural Research Service US Department of Agriculture, Greenport, NY 11944, USA; Oak Ridge Institute for Science and Education, PIADC Research Participation Program, Oak Ridge, TN 37831, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Kloc
authors.affiliation: Plum Island Animal Disease Center (PIADC), North Atlantic Area, Agricultural Research Service US Department of Agriculture, Greenport, NY 11944, USA.
authors.forename: Fayna
authors.initials: F
authors.lastname: Díaz-San Segundo
authors.affiliation: Plum Island Animal Disease Center (PIADC), North Atlantic Area, Agricultural Research Service US Department of Agriculture, Greenport, NY 11944, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rieder
authors.affiliation: Plum Island Animal Disease Center (PIADC), North Atlantic Area, Agricultural Research Service US Department of Agriculture, Greenport, NY 11944, USA.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Grubman
authors.affiliation: Howard Hughes Medical Institute and the Department of Biochemistry & Biophysics, University of California, San Francisco, CA 94158, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: DeRisi
authors.affiliation: Plum Island Animal Disease Center (PIADC), North Atlantic Area, Agricultural Research Service US Department of Agriculture, Greenport, NY 11944, USA. Electronic address: teresa.delossantos@ars.usda.gov.
authors.forename: Teresa
authors.initials: T
authors.lastname: de Los Santos
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D006224:Cricetinae; D004265:DNA Helicases / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005536:Foot-and-Mouth Disease / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics; D013058:Mass Spectrometry; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013552:Swine; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: D016898:Interferon-alpha; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D010450:Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: ADNP; Brg1; Chromatin remodeling; FMDV; IFN; Innate immunity; L(pro); Leader; Repressor; Transcription