TY - JOUR
T1 - 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
AU - Gaudreault, Natasha
AU - Jones, Clinton
N1 - Funding Information:
This research was supported by grants from the USDA and Agriculture and Food Research Initiative Competitive Grants Program ( 08-00891 and 09-01653 ). A grant to the Nebraska Center for Virology (1P20RR15635), in particular the confocal microscopy core facility, also supported certain aspects of these studies. Natasha Gaudreault was partially supported by a fellowship from a Ruth L. Kirschstein National Research Service Award 1 T32 AIO60547 (National Institute of Allergy and Infectious Diseases).
PY - 2011/3
Y1 - 2011/3
N2 - 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 C3HC4 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 C3HC4 zinc RING finger is important for PML degradation. Surprisingly, bICP0 mutants with an intact C3HC4 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.
AB - 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 C3HC4 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 C3HC4 zinc RING finger is important for PML degradation. Surprisingly, bICP0 mutants with an intact C3HC4 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.
KW - BICP0
KW - Bovine herpesvirus 1
KW - PML
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U2 - 10.1016/j.virusres.2010.12.010
DO - 10.1016/j.virusres.2010.12.010
M3 - Article
C2 - 21215282
AN - SCOPUS:79951810405
VL - 156
SP - 17
EP - 24
JO - Virus Research
JF - Virus Research
SN - 0168-1702
IS - 1-2
ER -