Essential transcription regulator Rta of Epstein-Barr virus - functional and structural implications for new antiviral strategy

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Authors

BROM Tomáš JANOVIČ Tomáš STOJASPAL Martin KŮŘILOVÁ Eliška CHLUDILOVÁ Simona HOFR Ctirad

Year of publication 2022
Type Conference abstract
MU Faculty or unit

Faculty of Science

Citation
Description The Epstein-Barr virus (EBV) is one of the most common human viruses that infects more than 90% of the world population during their lifetime. EBV causes 200,000 cancer cases per year. EBV is associated with various premalignant lymphoproliferative diseases, including Hodgkin's lymphoma, gastric cancer, and nasopharyngeal carcinoma and is infectious mononucleosis [1]. Besides cancer, infectious mononucleosis and multiple sclerosis are linked to EBV [2, 3].

Replication and transcription activator (Rta) is essential for the EBV life cycle because Rta reactivates lytic phase of EBV from latency. Rta binds to Rta Response Element (RRE) localized on viral DNA and transactivates a series of lytic genes, including the viral lytic gene PAN [4]. Rta has not been structurally characterized yet. Furthermore, no direct homologies were identified compared to other known DNA binding or dimerization motifs [5].

Rta targeting with small molecules presents a new potential approach in the fight against EBV-associated diseases. Thus, a detailed understanding of the Rta structure and oligomeric state is critical for future rational anti-EBV drug design.

We will present the first structural characterization of Rta, Rta interactions with DNA and host proteins along with Rta localization in human cells.

1. Rezk S.A., Zhao X., and Weiss L.M., Epstein-Barr virus (EBV)–associated lymphoid proliferations, Human Pathology, 79, (2018), 18-41. 2. Williams H., Crawford D.H., Epstein-Barr virus: the impact of scientific advances on clinical practice, Blood, 107 (2006), 862–869. 3. Bjornevik, K., Cortese, M., Healy, B.C., Kuhle, J., Mina, M.J., Leng, Y., Elledge, S.J., Niebuhr, D.W., Scher, A.I., Munger, K.L., Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis, Science, 375, (2022), 296-301. 4. Feederle R., and Delecluse H., The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators, The EMBO Journal, 19, (2000), 3080-3089. 5. Necasova I., Stojaspal M., Motycakova E., Brom T., Janovic T., Hofr C., Transcriptional regulators of human oncoviruses: structural and functional implications for anticancer therapy, NAR Cancer, 4, (2022)

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