title: Structural basis underlying viral hijacking of a histone chaperone complex.
abstract: The histone H3.3 chaperone DAXX is implicated in formation of heterochromatin and transcription silencing, especially for newly infecting DNA virus genomes entering the nucleus. Epstein-Barr virus (EBV) can efficiently establish stable latent infection as a chromatinized episome in the nucleus of infected cells. The EBV tegument BNRF1 is a DAXX-interacting protein required for the establishment of selective viral gene expression during latency. Here we report the structure of BNRF1 DAXX-interaction domain (DID) in complex with DAXX histone-binding domain (HBD) and histones H3.3-H4. BNRF1 DID contacts DAXX HBD and histones through non-conserved loops. The BNRF1-DAXX interface is responsible for BNRF1 localization to PML-nuclear bodies typically associated with host-antiviral resistance and transcriptional repression. Paradoxically, the interface is also required for selective transcription activation of viral latent cycle genes required for driving B-cell proliferation. These findings reveal molecular details of virus reprogramming of an antiviral histone chaperone to promote viral latency and cellular immortalization.
authors: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors: Hongda
authors: H
authors: Huang
authors: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors: Zhong
authors: Z
authors: Deng
authors: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors: Olga
authors: O
authors: Vladimirova
authors: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors: Andreas
authors: A
authors: Wiedmer
authors: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors: Fang
authors: F
authors: Lu
authors: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors: Paul M
authors: PM
authors: Lieberman
authors: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors: Dinshaw J
authors: DJ
authors: Patel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D056970:Co-Repressor Proteins; D057809:HEK293 Cells; D004854:Herpesvirus 4, Human / Q000235:genetics*; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D000072417:Protein Domains; D014759:Viral Envelope Proteins / Q000378:metabolism*; D017735:Virus Latency / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D056488:Histone Chaperones; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C062724:P140 protein, Epstein-barr virus; D014759:Viral Envelope Proteins