Epstein-Barr virus BNRF1 destabilizes SMC5/6 cohesin complexes to evade its restriction of replication compartments.
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Authors
Yiu, Stephanie Pei Tung
Guo, Rui
Zerbe, Cassie
Weekes, Michael P
Gewurz, Benjamin E
Publication Date
2022-03-08Journal Title
Cell Rep
ISSN
2211-1247
Publisher
Elsevier BV
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Yiu, S. P. T., Guo, R., Zerbe, C., Weekes, M. P., & Gewurz, B. E. (2022). Epstein-Barr virus BNRF1 destabilizes SMC5/6 cohesin complexes to evade its restriction of replication compartments.. Cell Rep https://doi.org/10.1016/j.celrep.2022.110411
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.
Sponsorship
Wellcome Trust (108070/Z/15/Z)
Identifiers
External DOI: https://doi.org/10.1016/j.celrep.2022.110411
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334176
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