title: Regulation of promyelocytic leukemia (PML) protein levels and cell morphology by bovine herpesvirus 1 infected cell protein 0 (bICP0) and mutant bICP0 proteins that do not localize to the nucleus.
abstract: BHV-1 is an important pathogen of cattle. The infected cell protein 0 (bICP0) encoded by BHV-1 is an important regulatory protein because it is constitutively expressed and can activate all viral promoters. The mechanism by which bICP0 activates viral promoters is not well understood because bICP0 does not appear to be a sequence specific binding protein. A C(3)HC(4) zinc RING (really interesting novel gene) motif at the N-terminus of bICP0 has E3 ubiquitin ligase activity, which is important for activating viral gene expression and inhibiting interferon dependent transcription. Like other alpha-herpesvirinae ICP0 homologues, bICP0 is associated with promyelocytic leukemia (PML) protein-containing nuclear domains. During productive infection of cultured cells, BHV-1 induces degradation of the PML protein, which correlates with efficient productive infection. In this study, we demonstrated that a plasmid expressing bICP0 reduces steady state levels of the PML protein, and the C(3)HC(4) zinc RING finger is important for PML degradation. Surprisingly, bICP0 mutants with an intact C(3)HC(4) zinc RING finger that lack a nuclear localization signal also reduces steady PML protein levels. In addition, mutant bICP0 proteins that primarily localize to the cytoplasm induced morphological changes in transfected cells. During productive infection, bICP0 was detected in the cytoplasm of low-passage bovine kidney, but not established bovine kidney cells. These studies demonstrated that bICP0, even when not able to efficiently localize to the nucleus, was able to induce degradation of the PML protein and alter the morphology of transfected cells.
authors.affiliation: School of Biological Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, United States.
authors.forename: Natasha
authors.initials: N
authors.lastname: Gaudreault
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D000818:Animals; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006566:Herpesviridae Infections / Q000473:pathology*; D007242:Herpesvirus 1, Bovine / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011817:Rabbits; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C086729:bICP0 protein, Bovine herpesvirus 1; D046988:Proteasome Endopeptidase Complex