# Spatiotemporal Gene Regulation and KSHV Replication

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $359,138

## Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) genomic episomes dynamically move in three-
dimensional (3D) nuclear space to ultimately aggregate in reactivating cells. Cellular RNA polymerase II (RNA
pol II) also translocates onto the aggregated viral genomes, resulting in the formation of viral transcriptional
factories. This previously uncharacterized mechanism represents an additional layer of KSHV gene regulation,
which facilitates the reutilization and repurposing of the limited quantities of cellular RNA pol II for effective viral
gene expression. Understanding this mechanism may allow us to identify new targets to inhibit viral
replication.
 In this application, we propose a comprehensive study to (1) identify the key cellular proteins involved
with viral transcriptional factory structure or function; (2) determine the role of noncoding PAN RNA transcripts
and its genomic region in viral transcriptional factory formation; and (3) visualize the physical assembly of viral
transcriptional factories in the nuclei of reactivated host cells using live 3D fluorescence microscopy. We will
also characterize the molecular architecture of viral transcriptional factories by super-resolution optical
microscopy with correlative electron microscopic imaging. Through this multifaceted approach, we hope to
understand the role of viral transcriptional factories in the amplification of KSHV gene expression, which may in
turn lead to the development of new therapeutic strategies for KSHV-associated malignancies by inhibiting viral
replication. In addition, we expect this investigation will shed light on the spatio-temporal (4D) organization of
the cell nucleome: using KSHV as a well-defined model chromosome that we can readily track in the host cell
nucleus with biochemical and genetic approaches.

## Key facts

- **NIH application ID:** 10436841
- **Project number:** 5R01CA225266-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Yoshihiro Izumiya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $359,138
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436841

## Citation

> US National Institutes of Health, RePORTER application 10436841, Spatiotemporal Gene Regulation and KSHV Replication (5R01CA225266-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10436841. Licensed CC0.

---

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