Disruption of PML-associated nuclear bodies during human cytomegalovirus infection.
PML is a protein associated with discrete spherical structures within the nucleus of normal cells. A defect in PML expression is observed in acute promyelocytic leukaemia as a consequence of a chromosomal translocation involving the genes encoding PML and the alpha retinoic acid receptor (RAR alpha). Disruption of PML bodies also occurs during herpes simplex virus infection after the immediate early protein Vmw110 has become associated with PML bodies. In this study, we followed the fate of PML bodies in human fibroblasts during the course of a human cytomegalovirus (CMV) infection. Disruption of PML bodies was observed to be dependent on de novo CMV gene expression and to occur within 4 h post-infection, concomitant with the onset of CMV IE gene expression. Although a transient increase in the number of PML bodies could be observed in some cells, PML exists predominantly as a diffuse nuclear protein during both the early and late stages of CMV infection. Although the function of PML bodies is still uncertain, their disruption may be important for efficient herpes virus replication.
Kelly
C
C
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Van Driel
R
R
Wilkinson
G W
GW
D016475:3T3 Cells; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002467:Cell Nucleus; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D000071156:Promyelocytic Leukemia Protein; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins
D000914:Antibodies, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D011500:Protein Synthesis Inhibitors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; C070576:PML protein, human; D003513:Cycloheximide; D010746:Phosphonoacetic Acid