# A dual role for APOBEC counteraction in EBV infection

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2021 · $8,207

## Abstract

A Dual Role for APOBEC Counteraction in EBV Infection
ABSTRACT
 Epstein-Barr Virus (EBV) is an oncogenic virus responsible for ~200,000 new cases of cancer each year.
EBV-associated cancers include a highly aggressive type of nasopharyngeal carcinoma (NPC) that is endemic
to regions of SE Asia. Studies on EBV biology and NPC pathogenesis have failed to establish a mechanistic
explanation for why people in these geographic areas have a 50-fold increase in EBV-positive NPC in
comparison to Western countries. A major requirement for the development of this malignancy is overcoming
the growth arrest induced by EBV infection in epithelial cells, thereby allowing longer-term virus persistence.
Thus, it is possible that genetic alterations in SE Asians may promote cell cycle progression and favor the
development of NPC. Our lab has recently discovered a novel role for the EBV protein BORF2, which had
previously been implicated in causing growth arrest during lytic infection. We found that BORF2 mediates
evasion of intracellular immunity by directly binding to the antiviral DNA deaminase APOBEC3B (A3B). This
interaction causes both proteins to relocalize to cytoplasmic aggregates and effectively protects the viral genome
from A3B-catalyzed mutation. In independent work, we have also shown that A3B binds the cyclin-dependent
kinase CDK4. Taken together, these studies lead me to hypothesize a dual role for BORF2 in nasopharyngeal
epithelial cells – protecting the EBV genome from deamination by A3B and promoting cell cycle arrest through
simultaneous sequestration of CDK4. This hypothesis will be tested through two Specific Aims. The first will
focus on fully characterizing the BORF2-A3B interaction through genetic, biochemical, and cell biological studies.
The second will determine the role of the BORF2-A3B interaction in causing cell cycle arrest and promoting EBV
lytic infection. In this aim I will also analyze genomic datasets to determine whether a SE Asia-biased A3B-
deletion allele predisposes to NPC. These studies will elucidate the mechanism through which BORF2
relocalizes A3B to avoid restriction, as well as reveal a novel role for this interaction in cell cycle modulation. A
clear delineation of these molecular mechanisms will advance knowledge and aid in the development of
therapies to EBV infection. Equally important, defining a role for this interaction in shaping EBV infection
trajectories may establish a geographically-biased A3B deletion allele as an NPC susceptibility marker.

## Key facts

- **NIH application ID:** 10233460
- **Project number:** 1F31AI161910-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sofia Moraes
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,207
- **Award type:** 1
- **Project period:** 2021-07-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233460

## Citation

> US National Institutes of Health, RePORTER application 10233460, A dual role for APOBEC counteraction in EBV infection (1F31AI161910-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10233460. Licensed CC0.

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