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dc.contributor.authorWood, J.J.
dc.contributor.authorBoyne, James R.
dc.contributor.authorPaulus, C.
dc.contributor.authorJackson, B.R.
dc.contributor.authorNevels, M.M.
dc.contributor.authorWhitehouse, A.
dc.contributor.authorHughes, D.J.
dc.date.accessioned2016-08-16T10:02:25Z
dc.date.available2016-08-16T10:02:25Z
dc.date.issued2016-08-10
dc.identifier.citationWood JJ, Boyne JR, Paulus C, Jackson BR et al (2016) ARID3B: A novel regulator of the Kaposi’s sarcoma-associated herpesvirus lytic cycle. Journal of Virology. 90(20): 9543–9555.en_US
dc.identifier.urihttp://hdl.handle.net/10454/8805
dc.descriptionYesen_US
dc.description.abstractKSHV is the causative agent of commonly fatal malignancies of immuno-compromised individuals, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). A hallmark of all herpesviruses is their biphasic lifecycle – viral latency and the productive lytic cycle, and it is well established that reactivation of the KSHV lytic cycle is associated with KS pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern reactivation is required to better understand disease progression. The viral protein, replication and transcription activator (RTA), is the KSHV lytic switch protein due to its ability to drive the expression of various lytic genes, leading to reactivation of the entire lytic cycle. While the mechanisms for activating lytic gene expression have received much attention, how RTA impacts on cellular function is less well understood. To address this, we developed a cell line with doxycycline-inducible RTA expression and applied SILAC-based quantitative proteomics. Using this methodology, we have identified a novel cellular protein (AT-rich interacting domain containing 3B, ARID3B) whose expression was enhanced by RTA and that relocalised to replication compartments upon lytic reactivation. We also show that siRNA knockdown or overexpression of ARID3B led to an enhancement or inhibition of lytic reactivation, respectively. Furthermore, DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B specifically interacts with A/T-rich elements in the KSHV origin of lytic replication (oriLyt), and this was dependent on lytic cycle reactivation. Therefore, we have identified a novel cellular protein whose expression is enhanced by KSHV RTA with the ability to inhibit KSHV reactivation.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1128/JVI.03262-15en_US
dc.rights2016 Wood et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/).en_US
dc.subjectKSHV, Kaposi's sarcoma-associated hepresvirus; Primary effusion lymphoma; PEL, Kaposi's sarcoma; KS; viral gene expression; Lytic reactivationen_US
dc.titleARID3B: A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycleen_US
dc.status.refereedYesen_US
dc.date.Accepted2016-07-15
dc.date.application2016-08-10
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
refterms.dateFOA2018-07-25T12:16:42Z


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