Determining the Significance of BORF2 Interaction with A3B and p53 in EBV Infection
Bibliographic record
Abstract
Epstein-Barr virus (EBV) is a human herpesvirus that infects over 90% of the world's population and is a causative agent of several types of cancers. EBV establishes lifelong infection in the host by alternating between latent and lytic infection. During the lytic phase of infection, the virus produces a cascade of ~70 proteins, many of which function to manipulate cellular processes to enable efficient production of virions. However, the functions of many of these proteins are poorly understood. In this study, I identified novel functions of the EBV lytic protein BORF2, that interacts with the cellular proteins APOBEC3B (A3B) and p53. A3B is a member of the APOBEC3 family of cytidine deaminases, which play a critical role in innate immune defense against viral infections by inducing hypermutation of viral genomes. p53 is a tumor suppressor protein that regulates the cell cycle and plays a critical role in G1/S arrest. Using affinity purification mass spectrometry (AP-MS), our lab discovered that BORF2 interacts with A3B and p53. I confirmed this interaction through proteomic and fluorescent microscopy experiments. My results also showed that BORF2 protects the viral genome by sequestering A3B away from the EBV replication compartment. Furthermore, we collaborated with the Harris lab at the University of Minnesota to perform infection assays which showed that BORF2 protects the EBV genome from A3B mutations. We also found that the interaction between BORF2 and A3B is conserved in KSHV with its viral protein ORF61, homologue of BORF2. In addition to its interaction with A3B, I showed that BORF2 induces p53 independently of A3B binding. My immunofluorescence microscopy experiments revealed that p53 bodies were juxtaposed to and not co-localized with BORF2-A3B bodies. However, in the absence of A3B, p53 co-localized with BORF2. My results suggest that A3B outcompetes p53 for the interaction with BORF2, leading us to propose a competition model where BORF2 can only induce G1/S through a p53-dependent manner in cells that express A3B. Therefore, my research has provided new insights into the mechanisms by which EBV protects its genome from A3B mutagenesis and contributes to G1/S arrest. The discovery of the mechanism by which EBV neutralizes A3B may provide opportunities for the development of therapeutic approaches against EBV as well as A3B-induced cancers.
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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) | 0.001 | 0.000 |
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".