a 2022

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

BROM, Tomáš; Tomáš JANOVIČ; Martin STOJASPAL; Eliška KŮŘILOVÁ; Simona CHLUDILOVÁ et. al.

Basic information

Original name

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

Authors

BROM, Tomáš; Tomáš JANOVIČ; Martin STOJASPAL; Eliška KŮŘILOVÁ; Simona CHLUDILOVÁ and Ctirad HOFR

Edition

Instruct Biennial Structural Biology Conference, 2022

Other information

Language

English

Type of outcome

Conference abstract

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Czech Republic

Confidentiality degree

is not subject to a state or trade secret

Organization unit

Faculty of Science
Changed: 7/10/2022 11:49, Mgr. Tomáš Brom, Ph.D.

Abstract

In the original language

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)

Links

CZ.02.2.69/0.0/0.0/19_073/0016943, interní kód MU
(CEP code: EF19_073/0016943)
Name: Interní grantová agentura Masarykovy univerzity (Acronym: IGA MU)
Investor: Ministry of Education, Youth and Sports of the CR, Priority axis 2: Development of universities and human resources for research and development
LM2018129, large research infrastructures
Name: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging
Investor: Ministry of Education, Youth and Sports of the CR
LM2018129, large research infrastructures
Name: National research infrastructure for biological and medical imaging
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1556/2021, interní kód MU
Name: Specifický výzkum v oblastech funkční genomiky a proteomiky (Acronym: SV-FGP)
Investor: Masaryk University