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The Epstein-Barr vi...
The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection
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- Li, Jinlin (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
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- Nagy, Noemi (author)
- Karolinska Institutet
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- Liu, Jiangnan (author)
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden,Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
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- Gupta, Soham (author)
- Karolinska Institutet
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- Frisan, Teresa, 1967- (author)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Umeå Centre for Microbial Research (UCMR),Umeå Univ, Dept Mol Biol, Umeå Ctr Microbial Res, Umeå, Sweden.
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- Hennig, Thomas (author)
- Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany,Univ Wurzburg, Inst Virol & Immunobiol, Wurzburg, Germany.
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- Cameron, Donald P. (author)
- Karolinska Institutet
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- Baranello, Laura (author)
- Karolinska Institutet
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- Masucci, Maria G. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2021-09-20
- 2021
- English.
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:9
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Abstract
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- Topoisomerases are essential for the replication of herpesviruses but the mechanisms by which the viruses hijack the cellular enzymes are largely unknown. We found that topoisomerase-II (TOP2) is a substrate of the Epstein-Barr virus (EBV) ubiquitin deconjugase BPLF1. BPLF1 co-immunoprecipitated and deubiquitinated TOP2, and stabilized SUMOylated TOP2 trapped in cleavage complexes (TOP2cc), which halted the DNA damage response to TOP2-induced double strand DNA breaks and promoted cell survival. Induction of the productive virus cycle in epithelial and lymphoid cell line carrying recombinant EBV encoding the active enzyme was accompanied by TOP2 deubiquitination, accumulation of TOP2ccs and resistance to Etoposide toxicity. The protective effect of BPLF1 was dependent on the expression of tyrosyl-DNA phosphodiesterase 2 (TDP2) that releases DNA-trapped TOP2 and promotes error-free DNA repair. These findings highlight a previously unrecognized function of BPLF1 in supporting a non-proteolytic pathway for TOP2cc debulking that favors cell survival and virus production.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Li, Jinlin
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Nagy, Noemi
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Liu, Jiangnan
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Gupta, Soham
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Frisan, Teresa, ...
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Hennig, Thomas
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show more...
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Cameron, Donald ...
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Baranello, Laura
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Masucci, Maria G ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
- Articles in the publication
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PLoS Pathogens
- By the university
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Umeå University
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Uppsala University
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Karolinska Institutet