PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0.
Promyelocytic leukemia (PML) nuclear bodies (also known as ND10) are nuclear substructures that contain several proteins, including PML itself, Sp100, and hDaxx. PML has been implicated in many cellular processes, and ND10 are frequently associated with the replicating genomes of DNA viruses. During herpes simplex virus type 1 (HSV-1) infection, the viral regulatory protein ICP0 localizes to ND10 and induces the degradation of PML, thereby disrupting ND10 and dispersing their constituent proteins. ICP0-null mutant viruses are defective in PML degradation and ND10 disruption, and concomitantly they initiate productive infection very inefficiently. Although these data are consistent with a repressive role for PML and/or ND10 during HSV-1 infection, evidence in support of this hypothesis has been inconclusive. By use of short interfering RNA technology, we demonstrate that depletion of PML increases both gene expression and plaque formation by an ICP0-negative HSV-1 mutant, while having no effect on wild-type HSV-1. We conclude that PML contributes to a cellular antiviral repression mechanism that is countered by the activity of ICP0.
Everett
Roger D
RD
MRC Virology Unit, Church Street, Glasgow G11 5JR, Scotland, United Kingdom. r.everett@mrcvu.gla.ac.uk
Rechter
Sabine
S
Papior
Peer
P
Tavalai
Nina
N
Stamminger
Thomas
T
Orr
Anne
A
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000378:metabolism; D034961:Antigens, Nuclear / Q000032:analysis / Q000378:metabolism; D001324:Autoantigens / Q000032:analysis / Q000378:metabolism; D056970:Co-Repressor Proteins; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D034961:Antigens, Nuclear; D001324:Autoantigens; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D017874:Immediate-Early Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C066642:SP100 protein, human; C070576:PML protein, human; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1