STAT3 Regulates Lytic Activation of Kaposi's Sarcoma-Associated Herpesvirus

Journal of Virology
Christine A KingSumita Bhaduri-McIntosh

Abstract

Lytic activation of Kaposi's sarcoma-associated herpesvirus (KSHV) from latency is a critical contributor to pathogenesis and progression of KSHV-mediated disease. Development of targeted treatment strategies and improvement of lytic-phase-directed oncolytic therapies, therefore, hinge on gaining a better understanding of latency-to-lytic-phase transition. A key observation in that regard, also common to other herpesviruses, is the partial permissiveness of latently infected cells to lytic-cycle-inducing agents. Here, we address the molecular basis of why only some KSHV-infected cells respond to lytic stimuli. Since cellular signal transducer and activator of transcription 3 (STAT3) is constitutively active in KSHV-associated cancers, KSHV activates STAT3, and STAT3 has been found to regulate lytic activation of Epstein-Barr virus (EBV)-infected cells, we asked if STAT3 contributes similarly to the life cycle of KSHV. We found that high levels of STAT3 correlate with the refractory state at the single-cell level under conditions of both spontaneous and induced lytic activation; importantly, STAT3 also regulates lytic susceptibility. Further, knockdown of STAT3 suppresses the cellular transcriptional corepressor Krüppel-associat...Continue Reading

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Citations

Feb 26, 2016·Frontiers in Microbiology·Suhani Thakker, Subhash C Verma
Jul 28, 2016·Frontiers in Microbiology·Xiaofan Li, Sumita Bhaduri-McIntosh
May 14, 2016·Cell Host & Microbe·Paul M Lieberman
Jan 20, 2017·Scientific Reports·Dhivya Ramalingam, Joseph M Ziegelbauer
Mar 30, 2017·Scientific Reports·Francis DoyleScott A Tenenbaum
Mar 16, 2018·PLoS Pathogens·Armando Andres Roca SuarezJoachim Lupberger
Apr 27, 2018·Journal of Virology·Xiaofan LiSumita Bhaduri-McIntosh
Sep 23, 2020·Viruses·Grant Broussard, Blossom Damania
Nov 11, 2018·Scientific Reports·Leonardo D'AiutoVishwajit Nimgaonkar
May 6, 2017·Frontiers in Microbiology·Kawalpreet K Aneja, Yan Yuan
Aug 17, 2020·Journal of Virology·Xiaofan LiSumita Bhaduri-McIntosh
Aug 28, 2020·Journal of Virology·Angela R Harrison, Gregory W Moseley
Mar 18, 2021·PLoS Pathogens·Eric M BurtonSumita Bhaduri-McIntosh
Aug 27, 2021·Frontiers in Microbiology·Tiffany R FreyMichael T McIntosh

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