# microRNA Regulation of Gamma-herpesvirus Latency and Reactivation

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $426,264

## Abstract

PROJECT SUMMARY
Epstein-Barr virus (EBV) persistently infects >90% of adults worldwide. In individuals with congenital or acquired
immune deficiencies, such as patients undergoing organ transplant or living with HIV/AIDS, life-long persistent
infection can lead to a variety of cancers. Like all herpesviruses, EBV has both a latent and a lytic replication
phase; the ability to switch between these programs is key to long-term viral persistence. Periodically, latent
EBV reactivates to produce infectious virus, which is thought to increase the pool of infected cells and sustain
persistent infection. Molecular mechanisms regulating latency and the switch to lytic replication are not entirely
understood. MicroRNAs (miRNAs) are small, non-coding regulatory RNAs that govern many biological
processes including cell state transitions and the development of immune responses. EBV encodes
evolutionarily conserved viral miRNAs that are active during stages of the viral life cycle when viral proteins are
highly restricted and that can interfere with host signaling pathways and anti-viral defense mechanisms on
multiple levels, leading us postulate that viral miRNAs represent an important part of why host immune responses
fail to clear persistent infection. Despite significant efforts advancing our understanding of EBV miRNA functions,
little is known about their contributions to infection in vivo. Based on preliminary findings, we hypothesize that
EBV miRNAs act as virulence factors and coordinate aspects of latency and reactivation that facilitate virus
persistence within a host. In this project, we will examine regulatory non-coding RNA interactions, asking
specifically how viral and cellular miRNAs cooperatively shape dynamic cell states during EBV infection, and
determine the miRNAs influencing critical decisions that impact virus reactivation. We aim to elucidate the critical
miRNAs and miRNA-mediated mechanisms (targets and pathways) regulating the EBV latent to lytic switch. To
test our hypothesis that viral miRNAs facilitate persistence in vivo, we will leverage the rhesus lymphocryptovirus
model to examine viral miRNA phenotypes in a natural primate host. Studies proposed herein have utility in
developing RNA-based therapeutic strategies against viral disease and important implications for advancing g-
herpesvirus vaccine development.

## Key facts

- **NIH application ID:** 9852590
- **Project number:** 5R01AI143620-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Rebecca L Skalsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $426,264
- **Award type:** 5
- **Project period:** 2019-01-22 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852590

## Citation

> US National Institutes of Health, RePORTER application 9852590, microRNA Regulation of Gamma-herpesvirus Latency and Reactivation (5R01AI143620-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9852590. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*