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Identification of Epstein-Barr virus BORF2 sequences required for APOBEC3B relocalization.
Farren Clark1, Michael A Carpenter2, Reuben S Harris2
1Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Journal of Virology
|August 21, 2025
Summary
Herpesviruses like EBV use the BORF2 protein to move APOBEC3B out of the nucleus, protecting viral DNA from mutation. A conserved motif and SUMOylation are key to this process.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Epstein-Barr virus (EBV) establishes lifelong infections and must protect its replicating DNA from host APOBEC3B deaminase.
- Herpesviruses employ viral proteins to counteract APOBEC3B, a host factor that mutates viral DNA.
Purpose of the Study:
- To investigate the conserved mechanisms herpesviruses use to sequester APOBEC3B.
- To identify the viral protein motifs and modifications involved in APOBEC3B relocalization and cytoplasmic body formation.
Main Methods:
- Analysis of conserved motifs (IPAM) in EBV BORF2, KSHV ORF61, and HSV-1 UL39.
- Investigating the role of a SUMO-modified site (K741) in BORF2.
- Characterizing cytoplasmic body formation and properties in the presence of viral proteins and APOBEC3B.
Main Results:
- A conserved IPAM motif is critical for BORF2, ORF61, and UL39 interaction with and relocalization of APOBEC3B.
- BORF2-induced cytoplasmic bodies require APOBEC3B, while UL39 bodies exhibit aggresome-like properties.
- SUMOylation at BORF2 K741 is important for cytoplasmic body formation with APOBEC3B, including in EBV-infected cells.
Conclusions:
- Herpesviruses utilize conserved protein motifs to disable APOBEC3B, safeguarding their genomes.
- SUMOylation of BORF2 plays a significant role in sequestering APOBEC3B into cytoplasmic bodies.
- Understanding these mechanisms is crucial for maintaining herpesvirus integrity and infectivity.
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