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Mutation of the Theiler’s virus leader protein zinc-finger domain impairs apoptotic activity in murine macrophages

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Title: Mutation of the Theiler’s virus leader protein zinc-finger domain impairs apoptotic activity in murine macrophages
Author(s): Son, Kyung-No; Liang, Zhiguo; Lipton, Howard L.
Subject(s): apoptosis leader protein Theiler’s virus
Abstract: The Theiler’s murine encephalomyelitis virus (TMEV) leader (L) protein zinc-finger domain was mutated to study its role in cell death in infection of the murine macrophage cell line M1-D, revealing that an intact zinc-finger domain is required for full apoptotic activity. A functional L zinc-finger domain was also required for activation of p38 MAPK that results in phosphorylation and activation of p53, and in turn, alteration of the conformation of the anti-apoptotic proteins Puma and Mcl-1, leading to the release of pro-apoptotic Bax and apoptosis through the intrinsic pathway. TMEV infection also inhibits host protein synthesis, a stress shown by others to induce apoptosis. Since inhibition of host protein synthesis follows rather than precedes activation of MKK3/6 and p38, it seems less likely that it triggers of apoptosis in infected cells. Finally, we showed that the levels of reactive oxygen species following infection were consistent with apoptotic rather than necrotic cell death. Thus, these experiments support an important role for the TMEV L protein zinc-finger domain in apoptosis in an infected murine macrophage line.
Issue Date: 2013-11
Publisher: Elsevier
Citation Info: Son KN, Liang Z, Lipton HL. Mutation of the Theiler's virus leader protein zinc-finger domain impairs apoptotic activity in murine macrophages. Virus Research. 2013 Nov 6;177(2):222-5. doi: 10.1016/j.virusres.2013.09.001.
Type: Article
Description: NOTICE: This is the author’s version of a work that was accepted for publication in Virus Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Virus Research, Vol 177, Issue 2, 2013 DOI: 10.1016/j.virusres.2013.09.001
URI: http://hdl.handle.net/10027/10910
ISSN: 1872-7492
Sponsor: This work was supported by NIH grant NS065945 and the Modestus Bauer Foundation.
Date Available in INDIGO: 2013-12-13
 

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