Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI

PLoS Pathogens

Lisa Marcinowski¹  Zsolt Ruzsics¹  Peter Wimmer²  Sabrina Schreiner²  Peter Groitl²  Thomas Dobner²  Guillaume Bossis³  Ruben Martinez⁴  Remi Vaillant⁴  Harald Wodrich⁴  Fabienne Rayne⁴  Thomas Sternsdorf⁵ 

[1] Gene Center Munich, Ludwig-Maximilian University, Munich, Munich, Germany;Heinrich–Pette–Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany;Institut Génétique Moléculaire de Montpellier, Université Montpellier 1, Université Montpellier 2, IGMM CNRS UMR 5535, Montpellier, France;Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université Bordeaux SEGALEN, Bordeaux, France;Research Institute, Children's Cancer Center, Hamburg, Germany

关键词: Viral packaging;    Gene expression;    Viral replication;    DNA transcription;    Tegument proteins;    Viral gene expression;    Viral genomics;    Viral genome;   

DOI  :  10.1371/journal.ppat.1002549

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents viral gene expression through the assembly of repressive chromatin remodeling complexes targeting incoming viral genomes. However, it has remained unclear how initial transcriptional activation of the adenoviral genome is achieved. Here we show that Daxx mediated repression of the immediate early Ad E1A promoter is efficiently counteracted by the capsid protein VI. This requires a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses were also shown to activate the Ad E1A promoter independent of Ad gene expression and support virus replication. Our results show how Ad entry is connected to transcriptional activation of their genome in the nucleus. Our data further suggest a common principle for genome activation of DNA viruses by counteracting Daxx related repressive mechanisms through virion proteins.

【 授权许可】

CC BY