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The anti-apoptotic Mcl-1 protein controls the type of cell death in Theiler’s virus-infected BHK-21 cells

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Title: The anti-apoptotic Mcl-1 protein controls the type of cell death in Theiler’s virus-infected BHK-21 cells
Author(s): Arslan, Sevim Yildiz; Son, Kyung-No; Lipton, Howard L.
Abstract: Theiler’s murine encephalomyelitis virus (TMEV) is a highly cytolytic RNA virus that produces a persistent central nervous system infection and immune-mediated demyelination in susceptible strains of mice. TMEV-infected macrophages (mφs) undergo apoptosis which reduces the yield of infectious progeny (<10 pfu/cell), whereas TMEV infection of other rodent cells in vitro, e.g. baby hamster kidney cells (BHK-21), produces a canonical necrotic cytopathic effect with high virus yields (200-500 pfu/cell). In this study, we found that while most TMEV-infected BHK-21 cells became necrotic, ~20% of cells underwent apoptosis. Mcl-1, an anti-apoptotic Bcl-2 family member, was highly expressed in BHK-21 cells, but levels decreased upon infection, consistent with the onset of apoptosis. Infection in BHK-21 cells in which Mcl-1 expression was knocked down using silencing (si) RNA that an ~ 3-fold increase in apoptotic cell death compared to that in parental cells. Infection of stable Mcl-1-knock-down cell lines led to restricted viral titers, unlike the high viral titers observed in parental cells. The apoptotic program switched on by TMEV replication appeared to be similar to that in mouse M1-D mφs, with hallmarks of activation of the intrinsic apoptotic pathway in a tumor suppressor protein p53-dependent manner. Subsequent activation of the Bcl-2 BH-only pro-apoptotic Noxa protein led to degradation of Mcl-1, activation of Bax and cleavage of caspases-9 and -3. Together, these results indicate that Mcl-1 acts as a critical pro-survival factor that protects against apoptosis in a p53-dependent manner and restricts the production of infectious virus in BHK-21 cells.
Issue Date: 2011
Publisher: American Society for Microbiology
Citation Info: Arslan, S. Y., Son, K. N., & Lipton, H. L. 2011. The anti-apoptotic Mcl-1 protein controls the type of cell death in Theiler's virus-infected BHK-21 cells. Journal of Virology . 86(4):1922-9. doi: 10.1128/​JVI.06516-11
Type: Article
Description: The original version is available through American Society for Microbiology at doi: 10.1128/​JVI.06516-11
URI: http://hdl.handle.net/10027/8471
ISSN: 0022-538X
Sponsor: This work was supported by NIH grant NS065945 and the Modestus Bauer Foundation.
Date Available in INDIGO: 2012-08-15
 

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