Identification of Epstein-Barr virus BORF2 sequences required for APOBEC3B relocalization
Bibliographic record
Abstract
Epstein-Barr virus (EBV) is a common herpesvirus that establishes lifetime infections in most people worldwide. To protect the lytically replicating EBV genomes from mutation, the EBV BORF2 protein relocalizes the APOBEC3B cytosine deaminase out of the nucleus, sequestering it in cytoplasmic bodies. This property is conserved in BORF2 homologs in other herpesviruses, including Kaposi's sarcoma-associated herpesvirus ORF61 and herpes simplex virus 1 UL39. Here, we show that a motif conserved in these three proteins (IPAM) is critical for interactions with and relocalization of APOBEC3B. However, the properties of the cytoplasmic bodies formed by BORF2, ORF61, and UL39 differ in that only BORF2 requires APOBEC3B to form cytoplasmic bodies, and only UL39 bodies have properties of aggresomes. We also found that a SUMO-modified site in BORF2 (K741) plays an important role in the formation of bodies with endogenous APOBEC3B, both when expressed on its own and in the context of EBV infection. Additionally, nuclear BORF2-APOBEC3B bodies that formed in early lytic infection contained SUMO, suggesting the importance of SUMOylation in the sequestration of APOBEC3B. Our study provides insights into the mechanisms herpesviruses use to disable APOBEC3B and protect their replicating DNA genomes from undesired editing.IMPORTANCEHerpesviruses must protect their replicating DNA genomes from mutation by APOBEC3B, which they do by relocalizing APOBEC3B from the nucleus into cytoplasmic bodies. This is mediated by Epstein-Barr virus BORF2 and its homologs in Kaposi's sarcoma-associated herpesvirus (ORF61) and herpes simplex virus 1 (UL39). We have shown that a conserved motif in these proteins is critical for this function, and that a SUMO-modified site in BORF2 also plays an important role. This work provides insight into the mechanisms by which BORF2 and its homologs sequester and relocalize APOBEC3B, which is important for maintaining the integrity and infectivity of the respective herpesviruses.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".