A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation

PLoS Pathogens

Wilhelm Ching¹  Emre Koyuncu¹  Sonia Singh¹  Thomas Dobner¹  Thomas Speiseder¹  Barbara Hartl¹  Elisabeth Kremmer²  Christina Arbelo-Roman³  Chris Meier³ 

[1] Department of Molecular Virology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany;Institute for Molecular Immunology, Helmholtz Centre Munich, Munich, Germany;Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Hamburg, Germany

关键词: Adenoviruses;    Viral replication;    Transfection;    Cell fusion;    DNA-binding proteins;    Glutathione chromatography;    Cell staining;    Cell growth;   

DOI  :  10.1371/journal.ppat.1003273

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Adenoviral replication depends on viral as well as cellular proteins. However, little is known about cellular proteins promoting adenoviral replication. In our screens to identify such proteins, we discovered a cellular component of the ubiquitin proteasome pathway interacting with the central regulator of adenoviral replication. Our binding assays mapped a specific interaction between the N-terminal domains of both viral E1B-55K and USP7, a deubiquitinating enzyme. RNA interference-mediated downregulation of USP7 severely reduced E1B-55K protein levels, but more importantly negatively affected adenoviral replication. We also succeeded in resynthesizing an inhibitor of USP7, which like the knockdown background reduced adenoviral replication. Further assays revealed that not only adenoviral growth, but also adenoviral oncogene-driven cellular transformation relies on the functions of USP7. Our data provide insights into an intricate mechanistic pathway usurped by an adenovirus to promote its replication and oncogenic functions, and at the same time open up possibilities for new antiviral strategies.

【 授权许可】

CC BY