# Role of FOXK subfamily in KSHV infection

> **NIH NIH F31** · UNIVERSITY OF FLORIDA · 2024 · $44,982

## Abstract

Project Summary
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus with a biphasic lifecycle
associated with several diseases such as Kaposi's sarcoma and primary effusion lymphoma (PEL). It is
primarily spread through saliva making the oral cavity a critical site for initial infection. KSHV encodes an
immediate early virion-associated tegument protein that is vital for efficient lytic reactivation and virus
production. Following up on a proteomics study of KSHV factors in uninfected cells, our coimmunoprecipitation
and imaging analysis in primary effusion lymphoma (PEL) cells during lytic reactivation of KSHV demonstrated
that an immediate early protein of KSHV interacts with host transcription factors, FOXK1 and FOXK2. FOXK1
and FOXK2 belong to the Forkhead family of transcription factors. FOXK1 and FOXK2 are unique as they are
the only Forkhead proteins which carry a Forkhead-associated (FHA) domain. FOXK proteins are ubiquitously
expressed and play a key role in cellular processes such as cell cycle regulation, cancer development, and
autophagy regulation. Their role in KSHV infection is not well understood though. Preliminary data from this
proposal supports a pro-viral role for these host transcription factors during KSHV's lytic cycle. The purpose of
this project is to dissect the importance of the interaction between the immediate early KSHV tegument protein
and FOXK proteins and identify novel targets genome-wide of the immediate early KSHV tegument protein
during reactivation and de novo infection. A combination of genome-wide studies coupled with KSHV mutants
will be used to analyze how the FOXK and immediate early tegument proteins affects KSHV infection. In
summary, I predict that this novel host-pathogen interaction might be engaged by KSHV, in order to promote
its lytic cycle in the oral cavity and beyond, thus by understanding the mechanism, we could uncover future
therapeutic targets. The completion of this project will provide in-depth training in epigenetics, virology and
genomics approaches. These skills will be enhanced in the outstanding research environment provided by the
Oral Biology department at the University of Florida College of Dentistry.

## Key facts

- **NIH application ID:** 10997917
- **Project number:** 1F31DE034303-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Marley Palmer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,982
- **Award type:** 1
- **Project period:** 2024-08-16 → 2027-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997917

## Citation

> US National Institutes of Health, RePORTER application 10997917, Role of FOXK subfamily in KSHV infection (1F31DE034303-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10997917. Licensed CC0.

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