The E3 Ubiquitin Ligase Mind Bomb 1 Controls Adenovirus Genome Release at the Nuclear Pore Complex

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http://hdl.handle.net/10138/311082

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Bauer , M , Flatt , J W , Seiler , D , Cardel , B , Emmenlauer , M , Boucke , K , Suomalainen , M , Hemmi , S & Greber , U F 2019 , ' The E3 Ubiquitin Ligase Mind Bomb 1 Controls Adenovirus Genome Release at the Nuclear Pore Complex ' , Cell Reports , vol. 29 , no. 12 , pp. 3785-3795.e8 . https://doi.org/10.1016/j.celrep.2019.11.064

Title: The E3 Ubiquitin Ligase Mind Bomb 1 Controls Adenovirus Genome Release at the Nuclear Pore Complex
Author: Bauer, Michael; Flatt, Justin W.; Seiler, Daria; Cardel, Bettina; Emmenlauer, Mario; Boucke, Karin; Suomalainen, Maarit; Hemmi, Silvio; Greber, Urs F.
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, University of Zurich
Date: 2019-12-17
Language: eng
Number of pages: 19
Belongs to series: Cell Reports
ISSN: 2211-1247
URI: http://hdl.handle.net/10138/311082
Abstract: Adenoviruses (AdVs) cause respiratory, ocular, and gastrointestinal tract infection and inflammation in immunocompetent people and life-threatening disease upon immunosuppression. AdV vectors are widely used in gene therapy and vaccination. Incoming particles attach to nuclear pore complexes (NPCs) of post-mitotic cells, then rupture and deliver viral DNA (vDNA) to the nucleus or misdeliver to the cytosol. Our genome-wide RNAi screen in AdV-infected cells identified the RING-type E3 ubiquitin ligase Mind bomb 1 (Mib1) as a proviral host factor for AdV infection. Mib1 is implicated in Notch-Delta signaling, ciliary biogenesis, and RNA innate immunity. Mib1 depletion arrested incoming AdVs at NPCs. Induced expression of full-length but not ligase-defective Mib1 in knockout cells triggered vDNA uncoating from NPC-tethered virions, nuclear import, misdelivery of vDNA, and vDNA expression. Mib1 is an essential host factor for AdV uncoating in human cells, and it provides a new concept for licensing virion DNA delivery through the NPC.
Subject: HERPES-SIMPLEX-VIRUS
MEMBRANE PENETRATION
CORE PROTEIN
SCREEN
DNA
ENTRY
PROTEASOME
IMPORT
SINGLE
NOTCH
1182 Biochemistry, cell and molecular biology
1183 Plant biology, microbiology, virology
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