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Manipulation of Promyelocytic Leukemia Protein Nuclear Bodies by Marek's Disease Virus Encoded US3 Protein Kinase.

ABSTRACT: Promyelocytic leukemia protein nuclear bodies (PML-NBs) are dynamic nuclear structures, shown to be important for herpesvirus replication; however, their role in regulating Marek's disease virus (MDV) infection has not been studied. MDV is an oncogenic alphaherpesvirus that causes lymphoproliferative disease in chickens. MDV encodes a US3 serine/threonine protein kinase that is important for MDV replication and gene expression. In this study, we studied the role of MDV US3 in regulating PML-NBs. Using an immunofluorescence assay, we found that MDV US3 disrupts PML and SP100 in a kinase dependent manner. In addition, treatment with MG-132 (a proteasome inhibitor) could partially restore the levels of PML and SP100, suggesting that a cellular proteasome dependent degradation pathway is involved in MDV US3 induced disruption of PML and SP100. These findings provide the first evidence for the interplay between MDV proteins and PML-NBs.

SUBMITTER: Liao Y

PROVIDER: S-EPMC8066686 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The alphaherpesvirus serine/threonine kinase us3 disrupts promyelocytic leukemia protein nuclear bodies.

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Amyloid precursor protein elevates fusion of promyelocytic leukemia nuclear bodies in human hippocampal areas with high plaque load.

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Identifying chromatin associations with promyelocytic leukemia nuclear bodies using immunoTRAP

Project description:Studies using fluorescence in situ hybridization (FISH) have attempted to determine whether specific gene loci associate with promyelocytic leukemia nuclear bodies (PML NBs). Two drawbacks accompany this approach; the lack of spatial resolution inherent with the technique, and the a priori basis for selecting which genes to probe. To overcome these limitations, we developed a technique, which we call immunoTRAP, which purifies the DNA contacting PML NBs at molecular dimensions. When we combined the immunoTRAP technique with immunoFISH and microarray analysis, not only did we verify a TP53-PML NB association, but were able also to identify novel locus associations such as PML, ABCA7, and TFF1. In addition, we observed that these associations are cell type specific, and induction of significantly higher levels of PML gene expression, as well as other physiological changes brought about by interferon treatment, can lead to a physical association of the PML gene with PML NBs in normal human fibroblasts. Thus, immunoTRAP is a technique capable of identifying the chromatin associations around nuclear subcompartments and is amenable for further downstream applications such as microarray analysis or deep sequencing.

2013-03-28 | GSE40554 | GEO

The Role of the Equine Herpesvirus Type 1 (EHV-1) US3-Encoded Protein Kinase in Actin Reorganization and Nuclear Egress.

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