EBV Tegument Protein BNRF1 Disrupts DAXX-ATRX to Activate Viral Early Gene Transcription

PLoS Pathogens

Henri-Jacques Delecluse¹  Nadezhda Thikmyanova¹  Paul M. Lieberman²  Jason A. Wojcechowskyj³  Kevin Tsai³ 

[1] Cell and Molecular Biology Program, The University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, United States of America;German Cancer Research Center, ATV-F100, Heidelberg, Germany;The Wistar Institute, Philadelphia, Pennsylvania, United States of America

关键词: Tegument proteins;    Viral gene expression;    B cells;    Nuclear bodies;    Transfection;    Epstein-Barr virus;    293T cells;    Viral replication;   

DOI  :  10.1371/journal.ppat.1002376

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus.

【 授权许可】

CC BY