Back to Search
Start Over
Epstein-Barr virus BNRF1 destabilizes SMC5/6 cohesin complexes to evade its restriction of replication compartments.
- Source :
-
Cell reports [Cell Rep] 2022 Mar 08; Vol. 38 (10), pp. 110411. - Publication Year :
- 2022
-
Abstract
- Epstein-Barr virus (EBV) persistently infects people worldwide. Delivery of ∼170-kb EBV genomes to nuclei and use of nuclear membrane-less replication compartments (RCs) for their lytic cycle amplification necessitate evasion of intrinsic antiviral responses. Proteomics analysis indicates that, upon B cell infection or lytic reactivation, EBV depletes the cohesin SMC5/6, which has major roles in chromosome maintenance and DNA damage repair. The major tegument protein BNRF1 targets SMC5/6 complexes by a ubiquitin proteasome pathway dependent on calpain proteolysis and Cullin-7. In the absence of BNRF1, SMC5/6 associates with R-loop structures, including at the viral lytic origin of replication, and interferes with RC formation and encapsidation. CRISPR analysis identifies RC restriction roles of SMC5/6 components involved in DNA entrapment and SUMOylation. Our study highlights SMC5/6 as an intrinsic immune sensor and restriction factor for a human herpesvirus RC and has implications for the pathogenesis of EBV-associated cancers.<br />Competing Interests: Declaration of interests B.E.G. receives support from an Abbvie-Harvard grant for research unrelated to these studies.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 38
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 35263599
- Full Text :
- https://doi.org/10.1016/j.celrep.2022.110411