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. 2019 Dec 21;12(1):17. doi: 10.3390/v12010017

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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KSHV activates UPR sensors but limits UPR gene expression during the lytic cycle. XBP1s is required for reactivation from latency in response to ER stress. All three UPR sensor proteins are activated in the early stages of lytic replication, but downstream UPR transcription is inhibited. ATF6-N is produced via proteolytic cleavage in the Golgi, but ATF6-N-responsive genes are not transcribed. IRE1 is activated and XBP1 is spliced, but XBP1s protein does not accumulate and XBP1s-responsive genes are not transcribed. eIF2α is phosphorylated in a PERK-dependent manner, but ATF4 protein does not accumulate and ATF4-responsive genes are not transcribed.