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Disruption of PML-associated nuclear bodies during human cytomegalovirus infection
C Kelly1, R Van Driel, G W Wilkinson
1Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Abstract:
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.
Insights
Human cytomegalovirus (CMV) infection disrupts promyelocytic leukemia (PML) bodies in fibroblasts. This disruption depends on new CMV gene expression and may aid herpesvirus replication.
Area of Science:
- Cell Biology
- Virology
- Molecular Biology
Background:
- Promyelocytic leukemia (PML) protein forms nuclear bodies in normal cells.
- PML defects are linked to acute promyelocytic leukemia and herpes simplex virus infections.
- The function of PML bodies remains largely unknown.
Purpose of the Study:
- To investigate the impact of human cytomegalovirus (CMV) infection on PML bodies in human fibroblasts.
- To determine the timing and dependency of PML body disruption during CMV infection.
Main Methods:
- Observation of PML body dynamics in human fibroblasts.
- Correlation of PML body changes with CMV gene expression, specifically immediate early (IE) genes.
Main Results:
- CMV infection leads to the disruption of PML bodies within 4 hours post-infection.
- PML body disruption is dependent on de novo CMV gene expression.
- PML protein appears as a diffuse nuclear component during early and late stages of CMV infection.
Conclusions:
- CMV infection significantly alters PML body structure.
- The disruption of PML bodies by CMV is linked to the onset of viral gene expression.
- PML body disruption might be crucial for efficient herpesvirus replication.