PMID:16873256

Citation	Everett, RD, Rechter, S, Papior, P, Tavalai, N, Stamminger, T and Orr, A (2006) PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0. J. Virol. 80:7995-8005
Abstract	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.
Links	PubMed PMC1563828 Online version:10.1128/JVI.00734-06
Keywords	Adaptor Proteins, Signal Transducing/analysis; Adaptor Proteins, Signal Transducing/metabolism; Antigens, Nuclear/analysis; Antigens, Nuclear/metabolism; Autoantigens/analysis; Autoantigens/metabolism; Fibroblasts/chemistry; Fibroblasts/metabolism; Gene Expression; Gene Expression Regulation, Viral; Genome, Viral; Herpesvirus 1, Human/genetics; Herpesvirus 1, Human/metabolism; Humans; Immediate-Early Proteins/analysis; Immediate-Early Proteins/genetics; Immediate-Early Proteins/metabolism; Neoplasm Proteins/antagonists & inhibitors; Neoplasm Proteins/genetics; Neoplasm Proteins/physiology; Nuclear Proteins/analysis; Nuclear Proteins/antagonists & inhibitors; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; RNA, Small Interfering/genetics; Transcription Factors/antagonists & inhibitors; Transcription Factors/genetics; Transcription Factors/physiology; Tumor Suppressor Proteins/antagonists & inhibitors; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/physiology; Ubiquitin-Protein Ligases/analysis; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PML	involved_in	GO:0002230: positive regulation of defense response to virus by host	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

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