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Updated: Jun 10, 2026
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Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
Epstein-Barr virus LF2 protein regulates viral replication by altering Rta subcellular localization
Andreas M F Heilmann1, Michael A Calderwood, Eric Johannsen
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Journal of Virology
|July 16, 2010
Summary
The Epstein-Barr virus (EBV) protein LF2 binds to Rta, relocating it outside the nucleus to inhibit viral replication. This mechanism controls the switch from latent to lytic EBV infection.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Epstein-Barr virus (EBV) lytic replication is regulated by viral transactivators Zta and Rta.
- The EBV protein LF2 was previously shown to inhibit Rta activity and block viral replication.
- LF2 also induces SUMO2/3 modification of Rta.
Purpose of the Study:
- To investigate the mechanism by which LF2 inhibits Rta activity and blocks EBV replication.
- To determine the role of Rta sumoylation and relocalization in LF2-mediated repression.
Main Methods:
- Coexpression studies in cell lines.
- Mapping of LF2 binding site on Rta using amino acid sequences.
- Mutational analysis of LF2.
- Analysis of viral gene expression (BLRF2, BMRF1) in different EBV-infected cell lines.
Main Results:
- LF2 sequesters Rta to the extranuclear cytoskeleton, inhibiting Rta promoter activation and EBV replication.
- LF2 binds Rta between amino acids 476-519, critical for Rta relocalization and repression.
- Rta redistribution is essential for repression, as demonstrated by mutational analysis of LF2.
- Rta localization changes during replication in LF2-positive cells (P3HR1) but not LF2-negative cells (B95-8).
- BLRF2 expression is reduced in P3HR1 cells, correlating with decreased Rta activity.
Conclusions:
- LF2 regulates EBV replication by binding to Rta and sequestering it outside the nucleus.
- This mechanism is crucial for controlling the switch between EBV latent and lytic infection stages.
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