title: PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication.
abstract: Intrinsic antiviral resistance mediated by constitutively expressed cellular proteins is one arm of defence against virus infection. Promyelocytic leukaemia nuclear bodies (PML-NBs, also known as ND10) contribute to host restriction of herpes simplex virus type 1 (HSV-1) replication via mechanisms that are counteracted by viral regulatory protein ICP0. ND10 assembly is dependent on PML, which comprises several different isoforms, and depletion of all PML isoforms decreases cellular resistance to ICP0-null mutant HSV-1. We report that individual expression of PML isoforms I and II partially reverses the increase in ICP0-null mutant HSV-1 plaque formation that occurs in PML-depleted cells. This activity of PML isoform I is dependent on SUMO modification, its SUMO interaction motif (SIM), and each element of its TRIM domain. Detailed analysis revealed that the punctate foci formed by individual PML isoforms differ subtly from normal ND10 in terms of composition and/or Sp100 modification. Surprisingly, deletion of the SIM motif from PML isoform I resulted in increased colocalisation with other major ND10 components in cells lacking endogenous PML. Our observations suggest that complete functionality of PML is dependent on isoform-specific C-terminal sequences acting in concert.
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Church Street, Glasgow G11 5JR, Scotland, UK.
authors.forename: Delphine
authors.initials: D
authors.lastname: Cuchet
authors.forename: Amanda
authors.initials: A
authors.lastname: Sykes
authors.forename: Armel
authors.initials: A
authors.lastname: Nicolas
authors.forename: Anne
authors.initials: A
authors.lastname: Orr
authors.forename: Jill
authors.initials: J
authors.lastname: Murray
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Sirma
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
authors.forename: Alexander
authors.initials: A
authors.lastname: Bartelt
authors.forename: Roger D
authors.initials: RD
authors.lastname: Everett
mesh_terms: D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1