title: The alphaherpesvirus serine/threonine kinase us3 disrupts promyelocytic leukemia protein nuclear bodies.
abstract: Us3, a serine/threonine kinase encoded by all alphaherpesviruses, plays diverse roles during virus infection, including preventing virus-induced apoptosis, facilitating nuclear egress of capsids, stimulating mRNA translation and promoting cell-to-cell spread of virus infection. Given this diversity, the full spectrum of Us3 function may not yet be recognized. We noted, in transiently transfected cells, that herpes simplex virus type 2 (HSV-2) Us3 disrupted promyelocytic leukemia protein nuclear bodies (PML-NBs). However, PML-NB disruption was not observed in cells expressing catalytically inactive HSV-2 Us3. Analysis of PML-NBs in Vero cells transfected with pseudorabies virus (PRV) Us3 and those in Vero cells infected with Us3-null or -repaired PRV strains indicated that PRV Us3 expression also leads to the disruption of PML-NBs. While loss of PML-NBs in response to Us3 expression was prevented by the proteasome inhibitor MG132, Us3-mediated degradation of PML was not observed in infected cells or in transfected cells expressing enhanced green fluorescent protein (EGFP)-tagged PML isoform IV. These findings demonstrate that Us3 orthologues derived from distantly related alphaherpesviruses cause a disruption of PML-NBs in a kinase- and proteasome-dependent manner but, unlike the alphaherpesvirus ICP0 orthologues, do not target PML for degradation.
authors.affiliation: Department of Microbiology and Immunology, Queen's University, Ontario, Canada.
authors.forename: Masany
authors.initials: M
authors.lastname: Jung
authors.forename: Renée L
authors.initials: RL
authors.lastname: Finnen
authors.forename: Casey E
authors.initials: CE
authors.lastname: Neron
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Banfield
mesh_terms: D000818:Animals; D002460:Cell Line; D018258:Herpesvirus 2, Human / Q000201:enzymology*; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C070576:PML protein, human; D017346:Protein Serine-Threonine Kinases; C084395:US3 protein, Human herpesvirus 2