Replication and transcription regulator Rta of Epstein-Barr virus - functional and structural implications for new antiviral strategy
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| Year of publication | 2025 |
| Type | Conference abstract |
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| Description | The Epstein-Barr virus (EBV) is one of the most prevalent human viruses, infecting over 90% of the global population over the course of a lifetime. EBV is implicated in approximately 200 000 cancer cases annually and is associated with various premalignant lymphoproliferative disorders, including Hodgkin's lymphoma, gastric carcinoma, and nasopharyngeal carcinoma. Beyond its oncogenic potential, EBV has been linked to infectious mononucleosis and multiple sclerosis. The replication and transcription activator (Rta) is a key regulator of the EBV life cycle, as Rta mediates the transition from latency to the lytic phase. Rta functions as a transcriptional activator by binding to the Rta Response Element (RRE) on viral DNA, thereby initiating the expression of lytic genes, including the viral gene PAN. Despite Rta functional significance, the structural properties of Rta remain uncharacterized, and no sequence homology has been identified between Rta and known DNA-binding or dimerization motifs. In this study, we employed an interdisciplinary approach to elucidate the functional and structural properties of Rta. We characterized the biophysical attributes of Rta DNA-binding domain and examined Rta oligomerization. Additionally, we investigated the structural features of the DNA-binding domain and quantified Rta binding affinity for a DNA sequence containing the RRE motif. In parallel, we analyzed Rta function in a human cell line, focusing on Rta nuclear localization and sequestration from nucleoli. Targeting Rta with small-molecule inhibitors represents a promising strategy for therapeutic intervention in EBV-associated diseases. Thus, a comprehensive understanding of Rta’s structural organization and oligomeric state is crucial for the rational design of novel antiviral agents. |
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