# EBV infection control by RNA surveillance

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2020 · $1,250

## Abstract

PROJECT SUMMARY
 Both establishment of latency by Epstein–Barr virus (EBV) and the virus’ ability to
reactivate are prerequisites for EBV-associated diseases including B cell- and epithelial cell-
derived malignancies. Yet, large gaps in knowledge about the host cell-intrinsic factors that
regulate the establishment and maintenance of EBV latency and the life cycle of EBV overall
exist.
 Among the host innate immune/intrinsic mechanisms that are critical for controlling virus
replication are several RNA surveillance pathways, most prominently the ones initiated by
intracellular RNA sensors, such as RIG-I-like receptors, that induce interferon-mediated antiviral
responses. Another important eukaryotic RNA surveillance pathway is the nonsense-mediated
mRNA decay (NMD) pathway which recognizes and rapidly degrades certain RNAs. Whereas
the role of the NMD machinery in the regulation of cellular processes has been well defined,
significantly less is known about the relevance of NMD-mediated RNA decay in controlling virus
replication. Intriguingly, a series of recent studies demonstrated that the NMD pathway is critical
for restricting the replication of several RNA viruses; however, whether NMD-mediated RNA
decay plays a role in controlling the life cycle of DNA viruses, and in particular gamma-
herpesviruses such as EBV, is currently unknown.
 The long-term goal of this study is to understand the physiological relevance of the NMD
RNA surveillance machinery in controlling the EBV life cycle (Aim 1). We will utilize molecular
and biochemical assays combined with next-generation RNA sequencing to determine the
precise RNAs targeted by the NMD machinery in EBV-infected cells, and further elucidate the
role of degradation of these RNAs in controlling EBV latent infection and reactivation in various
relevant cell types (Aim 2). Finally, we will determine the role of NMD-mediated RNA
surveillance in EBV-induced oncogenesis (Aim 3).
 The research proposed in this application is innovative because it investigates the role of
a novel intrinsic host mechanism in EBV infection control and EBV-induced tumorigenesis.
Furthermore, the proposed studies are important as they will significantly expand our knowledge
about host regulation of EBV infection and likely guide the design of novel therapeutic
strategies.

## Key facts

- **NIH application ID:** 9968027
- **Project number:** 5R21AI148082-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Michaela Ulrike Gack
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,250
- **Award type:** 5
- **Project period:** 2019-07-01 → 2020-07-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968027

## Citation

> US National Institutes of Health, RePORTER application 9968027, EBV infection control by RNA surveillance (5R21AI148082-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9968027. Licensed CC0.

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