Genome-Wide Transcriptional Roles of KSHV Viral Interferon Regulatory Factors in Oral Epithelial Cells.
Seung Jin JangNatalie AtyeoMario MietzschMin Y ChaeRobert McKennaZsolt TothBernadett PappPublished in: Viruses (2024)
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.
Keyphrases
- genome wide
- transcription factor
- genome wide identification
- dna binding
- amino acid
- dna methylation
- sars cov
- dendritic cells
- immune response
- copy number
- gene expression
- single cell
- bioinformatics analysis
- signaling pathway
- genome wide analysis
- poor prognosis
- stem cells
- palliative care
- high resolution
- induced apoptosis
- mass spectrometry
- inflammatory response
- pluripotent stem cells
- small molecule
- toll like receptor
- heat shock protein
- bone marrow