# Gene regulatory role of vIRF1 in KSHV infection

> **NIH NIH F30** · UNIVERSITY OF FLORIDA · 2022 · $45,319

## Abstract

Abstract
Infection of humans by the oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) starts in the oral cavity
by replicating in oral epithelial cells. Regulation of lytic KSHV infection of the oral epithelium is still poorly
understood, which hampers the development of effective antiviral therapies to block KSHV transmission. One of
the unique features of KSHV is that it encodes four different viral interferon regulatory factors (vIRFs), which are
homologous with cellular interferon regulatory factors (IRFs). One of them is vIRF1, which is expressed the
earliest and at the highest level during KSHV infection and is used by KSHV to control many different aspects of
the pathogenesis such as blocking antiviral response or stimulating oncogenesis and the growth of infected cells.
While the function of vIRF1 in the inhibition of different immune response signaling pathways have been studied
in detail, the transcriptional function of vIRF1 in the regulation of both KSHV and host cellular genes that are
important in viral pathogenesis is still poorly understood. vIRF1 is 449 amino acid long protein. It has a putative
DNA-binding domain (DBD), which also contains a nuclear localization signal (NLS), and it has a C-terminal IRF
interaction domain (IAD). My preliminary experiments revealed that the DNA-binding domain (DBD) of vIRF1 is
required for vIRF1-mediated host and viral gene induction, indicating vIRF1 induces both viral and host genes
by binding to their promoters. Our research group has also identified the viral and host proteins interacting with
vIRF1 by protein complex purification. This revealed the interaction of vIRF1 with histone acetyltransferases
(HATs) that often serve as co-factors for various DNA-binding transcription factors in gene induction. I
hypothesize that vIRF1 can bind to specific host and viral promoters and uses HATs to induce their
corresponding genes to enhance the lytic KSHV infection in oral epithelial cells. I propose two specific aims to
test my hypothesis. Aim 1 focuses on identifying the host genes that are directly targeted by vIRF1 in the absence
of the other vIRFs in KSHV-infected oral epithelial cells. Aim 2 is to determine the vIRF1 response element in
vIRF1 target KSHV promoters that is required for vIRF1-mediated promoter activation. The completion of this
project will provide in-depth training in virology, epigenetics and genomics approaches as these methods will be
used to elucidate this critical host pathogen interactions. The Comprehensive Training Program in Oral Biology
at the University of Florida College of Dentistry will provide me an outstanding environment to prepare me for a
career as a dentist scientist by providing personalized mentorship and excellent clinical and research training.

## Key facts

- **NIH application ID:** 10464138
- **Project number:** 1F30DE031956-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Seung Jin Jang
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $45,319
- **Award type:** 1
- **Project period:** 2022-08-16 → 2024-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464138

## Citation

> US National Institutes of Health, RePORTER application 10464138, Gene regulatory role of vIRF1 in KSHV infection (1F30DE031956-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464138. Licensed CC0.

---

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