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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Functional interactions between the Epstein-Barr virus BZLF1 protein and the promyelocytic leukemia protein
Brandy L Bowling1, Amy L Adamson
1Department of Biology, University of North Carolina at Greensboro, Greensboro, NC 27402, USA.
Abstract:
The Epstein-Barr virus immediate-early protein BZLF1 (Z) has been shown to alter the cellular localization of the promyelocytic leukemia (PML) protein. PML has important implications for growth control, apoptosis, anti-viral effects and many more processes. Here we further examined the relationship between PML and the Epstein-Barr virus Z protein. We examined the effect of Z expression on PML protein levels, and the effect of increased PML protein levels on Z-mediated dispersion of PML bodies. We found that increased levels of PML protein, such as through interferon treatment, were able to suppress Z-mediated PML body dispersion. We also studied the consequences of PML dispersion by Z, by examining p21 transactivation, A20 transactivation, and MHC Class I presentation levels in Z-expressing cells. We found that, while Z-mediated dispersion of PML did not affect MHC Class I presentation, it did alter p21 and A20 expression. In addition, we found that increased levels of PML were able to prevent Z protein binding to mitotic chromosomes. Our work implies that the balance of PML and Z levels in cells may affect how each protein functions.
Insights
Epstein-Barr virus Z protein alters promyelocytic leukemia (PML) protein bodies. Increased PML levels suppress Z-mediated dispersion and prevent Z binding to mitotic chromosomes, impacting cellular functions.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- The Epstein-Barr virus immediate-early protein BZLF1 (Z) interacts with the promyelocytic leukemia (PML) protein.
- PML is crucial for cellular processes including growth control, apoptosis, and antiviral responses.
- Understanding the interplay between Z and PML is vital for comprehending viral pathogenesis and cellular regulation.
Purpose of the Study:
- To investigate the reciprocal effects of Epstein-Barr virus Z protein and PML protein levels.
- To determine how Z expression impacts PML protein levels and PML body integrity.
- To analyze the functional consequences of Z-mediated PML body dispersion on cellular processes.
Main Methods:
- Expression of Z protein in cells.
- Interferon treatment to increase PML protein levels.
- Analysis of PML body localization and dispersion.
- Assessment of p21 and A20 transactivation.
- Evaluation of MHC Class I presentation levels.
- Investigation of Z protein binding to mitotic chromosomes.
Main Results:
- Increased PML protein levels, induced by interferon, suppressed Z-mediated PML body dispersion.
- Z-mediated PML dispersion altered p21 and A20 expression but did not affect MHC Class I presentation.
- Elevated PML levels prevented Z protein binding to mitotic chromosomes.
Conclusions:
- The balance between PML and Z protein levels critically influences their respective functions.
- PML acts as a suppressor of Z-mediated cellular alterations.
- This interaction provides insights into Epstein-Barr virus replication strategies and host cell manipulation.
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