# Genome-Wide Transcriptional Roles of KSHV Viral Interferon Regulatory Factors in Oral Epithelial Cells

## TL;DR

This study explores how KSHV's vIRFs affect gene regulation in oral epithelial cells, revealing distinct roles despite structural similarities.

## Contribution

The study identifies distinct gene regulation roles for each KSHV vIRF despite structural homology.

## Key findings

- vIRFs have high structural homology in DNA-binding and IRF association domains despite low sequence similarity.
- Each vIRF regulates distinct sets of KSHV and human genes in epithelial cells.
- The DNA-binding domain of vIRF1 is crucial for regulating its target genes.

## Abstract

The viral interferon regulatory factors (vIRFs) of KSHV are known to dysregulate cell signaling pathways to promote viral oncogenesis and to block antiviral immune responses to facilitate infection. However, it remains unknown to what extent each vIRF plays a role in gene regulation. To address this, we performed a comparative analysis of the protein structures and gene regulation of the four vIRFs. Our structure prediction analysis revealed that despite their low amino acid sequence similarity, vIRFs exhibit high structural homology in both their DNA-binding domain (DBD) and IRF association domain. However, despite this shared structural homology, we demonstrate that each vIRF regulates a distinct set of KSHV gene promoters and human genes in epithelial cells. We also found that the DBD of vIRF1 is essential in regulating the expression of its target genes. We propose that the structurally similar vIRFs evolved to possess specialized transcriptional functions to regulate specific genes.