Informace o publikaci
Transcriptional regulation of Epstein-Barr oncovirus – biophysical implications for Rta-targeted therapy
| Autoři | |
|---|---|
| Rok publikování | 2025 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Epstein–Barr virus (EBV), a common human ?-herpesvirus, is linked to lymphoid and epithelial cancers, mononucleosis, and autoimmune diseases like multiple sclerosis. Central to EBV’s oncogenic repertoire is the Replication and Transcription Activator (Rta), a viral transcription factor that orchestrates the switch from latency to lytic reactivation by binding its cognate Rta Response Element (RRE) on viral DNA and transactivating a cascade of lytic genes. We present a rigorous, quantitative dissection of Rta–DNA interactions, comparing full-length Rta with a variant lacking its intrinsically disordered region. Employing electrophoretic mobility shift assays, fluorescence anisotropy, and microscale thermophoresis, we derive precise binding affinities and stoichiometries with a fluorescently labeled RRE duplex. Integrating bioinformatic predictions, targeted mutagenesis, and high-resolution atomic force microscopy, we map the critical amino acids and domains that drive Rta’s DNA engagement. To link the biophysical mechanism with the cellular impact, we combine immunolocalization in EBV-positive model cells, molecular biology techniques, and structural analyses, revealing Rta’s nuclear distribution and its role in destabilizing the host chromosomal architecture. These insights illuminate how Rta contributes to the genomic chaos underlying EBV-associated pathologies. By elucidating the molecular choreography of Rta–DNA recognition and its influence on chromosomal integrity, our work uncovers new avenues for precision therapies aimed at eliminating EBV-associated diseases. |
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