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Article: Reactivation of Epstein-Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

TitleReactivation of Epstein-Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function
Authors
KeywordsEBV-specific lytic inducer
EBNA1-targeting agent
dual-responsive fluorescent EBV probe
Issue Date2019
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2019, v. 116 n. 52, p. 26614-26624 How to Cite?
AbstractEpstein–Barr nuclear antigen 1 (EBNA1) plays a vital role in the maintenance of the viral genome and is the only viral protein expressed in nearly all forms of Epstein–Barr virus (EBV) latency and EBV-associated diseases, including numerous cancer types. To our knowledge, no specific agent against EBV genes or proteins has been established to target EBV lytic reactivation. Here we report an EBNA1- and Zn2+-responsive probe (ZRL5P4) which alone could reactivate the EBV lytic cycle through specific disruption of EBNA1. We have utilized the Zn2+ chelator to further interfere with the higher order of EBNA1 self-association. The bioprobe ZRL5P4 can respond independently to its interactions with Zn2+ and EBNA1 with different fluorescence changes. It can selectively enter the nuclei of EBV-positive cells and disrupt the oligomerization and oriP-enhanced transactivation of EBNA1. ZRL5P4 can also specifically enhance Dicer1 and PML expression, molecular events which had been reported to occur after the depletion of EBNA1 expression. Importantly, we found that treatment with ZRL5P4 alone could reactivate EBV lytic induction by expressing the early and late EBV lytic genes/proteins. Lytic induction is likely mediated by disruption of EBNA1 oligomerization and the subsequent change of Dicer1 expression. Our probe ZRL5P4 is an EBV protein-specific agent that potently reactivates EBV from latency, leading to the shrinkage of EBV-positive tumors, and our study also suggests the association of EBNA1 oligomerization with the maintenance of EBV latency.
Persistent Identifierhttp://hdl.handle.net/10722/290629
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJiang, L-
dc.contributor.authorLung, HL-
dc.contributor.authorHuang, T-
dc.contributor.authorLan, R-
dc.contributor.authorZha, S-
dc.contributor.authorChan, LS-
dc.contributor.authorThor, W-
dc.contributor.authorTsoi, TH-
dc.contributor.authorChau, HF-
dc.contributor.authorBoreström, C-
dc.contributor.authorCobb, SL-
dc.contributor.authorTsao, SW-
dc.contributor.authorBian, ZX-
dc.contributor.authorLaw, GL-
dc.contributor.authorWong, WT-
dc.contributor.authorTai, WCS-
dc.contributor.authorChau, WY-
dc.contributor.authorDu, Y-
dc.contributor.authorTang, LHX-
dc.contributor.authorChiang, AKS-
dc.contributor.authorMiddeldorp, JM-
dc.contributor.authorLo, KW-
dc.contributor.authorMak, NK-
dc.contributor.authorLong, NJ-
dc.contributor.authorWong, KL-
dc.date.accessioned2020-11-02T05:44:55Z-
dc.date.available2020-11-02T05:44:55Z-
dc.date.issued2019-
dc.identifier.citationProceedings of the National Academy of Sciences, 2019, v. 116 n. 52, p. 26614-26624-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/290629-
dc.description.abstractEpstein–Barr nuclear antigen 1 (EBNA1) plays a vital role in the maintenance of the viral genome and is the only viral protein expressed in nearly all forms of Epstein–Barr virus (EBV) latency and EBV-associated diseases, including numerous cancer types. To our knowledge, no specific agent against EBV genes or proteins has been established to target EBV lytic reactivation. Here we report an EBNA1- and Zn2+-responsive probe (ZRL5P4) which alone could reactivate the EBV lytic cycle through specific disruption of EBNA1. We have utilized the Zn2+ chelator to further interfere with the higher order of EBNA1 self-association. The bioprobe ZRL5P4 can respond independently to its interactions with Zn2+ and EBNA1 with different fluorescence changes. It can selectively enter the nuclei of EBV-positive cells and disrupt the oligomerization and oriP-enhanced transactivation of EBNA1. ZRL5P4 can also specifically enhance Dicer1 and PML expression, molecular events which had been reported to occur after the depletion of EBNA1 expression. Importantly, we found that treatment with ZRL5P4 alone could reactivate EBV lytic induction by expressing the early and late EBV lytic genes/proteins. Lytic induction is likely mediated by disruption of EBNA1 oligomerization and the subsequent change of Dicer1 expression. Our probe ZRL5P4 is an EBV protein-specific agent that potently reactivates EBV from latency, leading to the shrinkage of EBV-positive tumors, and our study also suggests the association of EBNA1 oligomerization with the maintenance of EBV latency.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectEBV-specific lytic inducer-
dc.subjectEBNA1-targeting agent-
dc.subjectdual-responsive fluorescent EBV probe-
dc.titleReactivation of Epstein-Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function-
dc.typeArticle-
dc.identifier.emailChiang, AKS: chiangak@hku.hk-
dc.identifier.authorityChiang, AKS=rp00403-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1915372116-
dc.identifier.pmid31822610-
dc.identifier.pmcidPMC6936348-
dc.identifier.scopuseid_2-s2.0-85077308427-
dc.identifier.hkuros317756-
dc.identifier.volume116-
dc.identifier.issue52-
dc.identifier.spage26614-
dc.identifier.epage26624-
dc.identifier.isiWOS:000504656900068-
dc.publisher.placeUnited States-
dc.identifier.issnl0027-8424-

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