An essential role of ERK signalling in TPA-induced reactivation of Kaposi's sarcoma-associated herpesvirus

The Journal of General Virology
Adina CohenRonit Sarid

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is implicated causally in the development of several human malignancies, including primary effusion lymphoma (PEL). PEL cells serve as tools for KSHV research, as most of them are latently infected and allow lytic virus replication in response to various stimuli. 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) is the most potent inducer of lytic KSHV reactivation; nevertheless, the exact mechanism by which it induces reactivation remains unknown. It has previously been reported by our group that the protein kinase C (PKC) delta isoform plays a crucial role in TPA-mediated KSHV reactivation. Here, the activation pathway was dissected and it was demonstrated that TPA induces KSHV reactivation via stimulation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. Western blot analysis revealed a rapid phosphorylation of ERK1/2. Cells treated with MAPK/ERK inhibitors before TPA addition demonstrated repression of ERK1/2 phosphorylation, which was associated with a block of KSHV lytic-gene expression. This inhibition prevented c-Fos accumulation, yet increased c-Jun phosphorylation. Similar results were obtained in response to rottlerin, a select...Continue Reading

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Citations

Dec 8, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Xiaohui BiBetsy J Barnes
Jun 1, 2011·Advances in Virology·Fengchun YeShou-Jiang Gao
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Jan 18, 2014·Biochemical and Biophysical Research Communications·Kazufumi WakaoMasahiro Fujimuro
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May 6, 2017·Frontiers in Microbiology·Kawalpreet K Aneja, Yan Yuan
Jul 25, 2019·International Journal of Molecular Sciences·Jeanne K DuShane, Melissa S Maginnis
Dec 13, 2019·Fish & Shellfish Immunology·Ze-Quan MoXue-Ming Dan

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