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Article: Autophagy-Dependent Reactivation of Epstein-Barr Virus Lytic Cycle and Combinatorial Effects of Autophagy-Dependent and Independent Lytic Inducers in Nasopharyngeal Carcinoma

TitleAutophagy-Dependent Reactivation of Epstein-Barr Virus Lytic Cycle and Combinatorial Effects of Autophagy-Dependent and Independent Lytic Inducers in Nasopharyngeal Carcinoma
Authors
Keywordsautophagy
Epstein-Barr virus (EBV)
lytic reactivation
nasopharyngeal carcinoma (NPC)
lytic induction therapy
Issue Date2019
PublisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/
Citation
Cancers, 2019, v. 11 n. 12, p. article no. 1871 How to Cite?
AbstractAutophagy, a conserved cellular mechanism, is manipulated by a number of viruses for different purposes. We previously demonstrated that an iron-chelator-like small compound, C7, reactivates Epstein-Barr virus (EBV) lytic cycle by activating the ERK1/2-autophagy axis in epithelial cancers. Here, we aim to identify the specific stage of autophagy required for EBV lytic reactivation, determine the autophagy dependency of EBV lytic inducers including histone deacetylase inhibitor (HDACi) and C7/iron chelators, for EBV lytic reactivation and measure the combinatorial effects of these types of lytic inducers in nasopharyngeal carcinoma (NPC). Inhibition of autophagy initiation by 3-MA and autolysosome formation by chloroquine demonstrated that only autophagy initiation is required for EBV lytic reactivation. Gene knockdown of various autophagic proteins such as beclin-1, ATG5, ATG12, ATG7, LC3B, ATG10, ATG3 and Rab9, revealed the importance of ATG5 in EBV lytic reactivation. 3-MA could only abrogate lytic cycle induction by C7/iron chelators but not by HDACi, providing evidence for autophagy-dependent and independent mechanisms in EBV lytic reactivation. Finally, the combination of C7 and SAHA at their corresponding reactivation kinetics enhanced EBV lytic reactivation. These findings render new insights in the mechanisms of EBV lytic cycle reactivation and stimulate a rational design of combination drug therapy against EBV-associated cancers.
Persistent Identifierhttp://hdl.handle.net/10722/293499
ISSN
2023 Impact Factor: 4.5
2023 SCImago Journal Rankings: 1.391
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYIU, SPT-
dc.contributor.authorHui, KF-
dc.contributor.authorMünz, C-
dc.contributor.authorLo, KW-
dc.contributor.authorTsao, SW-
dc.contributor.authorKao, RYT-
dc.contributor.authorYang, D-
dc.contributor.authorChiang, AKS-
dc.date.accessioned2020-11-23T08:17:39Z-
dc.date.available2020-11-23T08:17:39Z-
dc.date.issued2019-
dc.identifier.citationCancers, 2019, v. 11 n. 12, p. article no. 1871-
dc.identifier.issn2072-6694-
dc.identifier.urihttp://hdl.handle.net/10722/293499-
dc.description.abstractAutophagy, a conserved cellular mechanism, is manipulated by a number of viruses for different purposes. We previously demonstrated that an iron-chelator-like small compound, C7, reactivates Epstein-Barr virus (EBV) lytic cycle by activating the ERK1/2-autophagy axis in epithelial cancers. Here, we aim to identify the specific stage of autophagy required for EBV lytic reactivation, determine the autophagy dependency of EBV lytic inducers including histone deacetylase inhibitor (HDACi) and C7/iron chelators, for EBV lytic reactivation and measure the combinatorial effects of these types of lytic inducers in nasopharyngeal carcinoma (NPC). Inhibition of autophagy initiation by 3-MA and autolysosome formation by chloroquine demonstrated that only autophagy initiation is required for EBV lytic reactivation. Gene knockdown of various autophagic proteins such as beclin-1, ATG5, ATG12, ATG7, LC3B, ATG10, ATG3 and Rab9, revealed the importance of ATG5 in EBV lytic reactivation. 3-MA could only abrogate lytic cycle induction by C7/iron chelators but not by HDACi, providing evidence for autophagy-dependent and independent mechanisms in EBV lytic reactivation. Finally, the combination of C7 and SAHA at their corresponding reactivation kinetics enhanced EBV lytic reactivation. These findings render new insights in the mechanisms of EBV lytic cycle reactivation and stimulate a rational design of combination drug therapy against EBV-associated cancers.-
dc.languageeng-
dc.publisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/-
dc.relation.ispartofCancers-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectautophagy-
dc.subjectEpstein-Barr virus (EBV)-
dc.subjectlytic reactivation-
dc.subjectnasopharyngeal carcinoma (NPC)-
dc.subjectlytic induction therapy-
dc.titleAutophagy-Dependent Reactivation of Epstein-Barr Virus Lytic Cycle and Combinatorial Effects of Autophagy-Dependent and Independent Lytic Inducers in Nasopharyngeal Carcinoma-
dc.typeArticle-
dc.identifier.emailTsao, SW: gswtsao@hku.hk-
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hk-
dc.identifier.emailYang, D: yangdan@hku.hk-
dc.identifier.emailChiang, AKS: chiangak@hku.hk-
dc.identifier.authorityTsao, SW=rp00399-
dc.identifier.authorityKao, RYT=rp00481-
dc.identifier.authorityYang, D=rp00825-
dc.identifier.authorityChiang, AKS=rp00403-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/cancers11121871-
dc.identifier.pmid31769432-
dc.identifier.pmcidPMC6966612-
dc.identifier.scopuseid_2-s2.0-85075754678-
dc.identifier.hkuros319368-
dc.identifier.hkuros317760-
dc.identifier.volume11-
dc.identifier.issue12-
dc.identifier.spagearticle no. 1871-
dc.identifier.epagearticle no. 1871-
dc.identifier.isiWOS:000507382100050-
dc.publisher.placeSwitzerland-
dc.identifier.issnl2072-6694-

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