Transcriptional regulation of Epstein-Barr oncovirus –
biophysical implications for Rta-targeted therapy

a 2025

Transcriptional regulation of Epstein-Barr oncovirus – biophysical implications for Rta-targeted therapy

BROM, Tomáš; Pavel VEVERKA; Jarmila MLČOUŠKOVÁ; Eva POSPÍŠILOVÁ; Tereza PAŘÍKOVÁ et al.

Základní údaje

Originální název

Transcriptional regulation of Epstein-Barr oncovirus – biophysical implications for Rta-targeted therapy

Autoři

BROM, Tomáš ; Pavel VEVERKA; Jarmila MLČOUŠKOVÁ; Eva POSPÍŠILOVÁ; Tereza PAŘÍKOVÁ a Ctirad HOFR

Vydání

4th Chromosomal Instability as a Driver of Human Disease Conference, 2025

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10608 Biochemistry and molecular biology

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

EBV; Rta

Změněno: 2. 2. 2026 13:59, Mgr. Tomáš Brom, Ph.D.

Anotace

V originále

Epstein–Barr virus (EBV), a common human γ-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.

Návaznosti

GA23-05241S, projekt VaV

Název: Regulace transkripce onkoviru Epstein–Barrové – biofyzikální implikace pro léčbu cílenou na transkripční regulátor Rta

Investor: Grantová agentura ČR, Regulace transkripce Epstein–Barr viru – biofyzikální implikace pro molekulární léčbu cílenou na transkripční regulátor Rta

Citovat

BROM, Tomáš; Pavel VEVERKA; Jarmila MLČOUŠKOVÁ; Eva POSPÍŠILOVÁ; Tereza PAŘÍKOVÁ a Ctirad HOFR. Transcriptional regulation of Epstein-Barr oncovirus – biophysical implications for Rta-targeted therapy. In 4th Chromosomal Instability as a Driver of Human Disease Conference. 2025.

@proceedings{2552017,
   author = {Brom, Tomáš and Veverka, Pavel and Mlčoušková, Jarmila and Pospíšilová, Eva and Paříková, Tereza and Hofr, Ctirad},
   booktitle = {4th Chromosomal Instability as a Driver of Human Disease Conference},
   keywords = {EBV; Rta},
   language = {eng},
   title = {Transcriptional regulation of Epstein-Barr oncovirus – biophysical implications for Rta-targeted therapy},
   url = {https://fusion-conferences.com/conference/184},
   year = {2025}
}

TY  - CONF
ID  - 2552017
AU  - Brom, Tomáš - Veverka, Pavel - Mlčoušková, Jarmila - Pospíšilová, Eva - Paříková, Tereza - Hofr, Ctirad
PY  - 2025
TI  - Transcriptional regulation of Epstein-Barr oncovirus – biophysical implications for Rta-targeted therapy
KW  - EBV
KW  - Rta
UR  - https://fusion-conferences.com/conference/184
N2  - Epstein–Barr virus (EBV), a common human γ-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.
ER  -

BROM, Tomáš; Pavel VEVERKA; Jarmila MLČOUŠKOVÁ; Eva POSPÍŠILOVÁ; Tereza PAŘÍKOVÁ a Ctirad HOFR. Transcriptional regulation of Epstein-Barr oncovirus – biophysical implications for Rta-targeted therapy. In \textit{4th Chromosomal Instability as a Driver of Human Disease Conference}. 2025.

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