title: The antiapoptotic protein Mcl-1 controls the type of cell death in Theiler's virus-infected BHK-21 cells.
abstract: Theiler's murine encephalomyelitis virus (TMEV) results in a persistent central nervous system infection (CNS) and immune-mediated demyelination in mice. TMEV largely persists in macrophages (Ms) in the CNS, and infected Ms in vitro undergo apoptosis, whereas the infection of other rodent cells produces necrosis. We have found that necrosis is the dominant form of cell death in BeAn virus-infected BHK-21 cells but that ~20% of cells undergo apoptosis. Mcl-1 was highly expressed in BHK-21 cells, and protein levels decreased upon infection, consistent with onset of apoptosis. In infected BHK-21 cells in which Mcl-1 expression was knocked down using silencing RNAs there was a 3-fold increase in apoptotic cell death compared to parental cells. The apoptotic program switched on by BeAn virus is similar to that in mouse Ms, with hallmarks of activation of the intrinsic apoptotic pathway in a tumor suppressor protein p53-dependent manner. Infection of stable Mcl-1-knockdown cells led to restricted virus titers and increased physical to infectious particle (PFU) ratios, with additional data suggesting that a late step in the viral life cycle after viral RNA replication, protein synthesis, and polyprotein processing is affected by apoptosis. Together, these results indicate that Mcl-1 acts as a critical prosurvival factor that protects against apoptosis and allows high yields of infectious virus in BHK-21 cells.
authors: Department of Microbiology-Immunology, University of Illinois at Chicago, Chicago, Illinois, USA.
authors: Sevim Yildiz
authors: SY
authors: Arslan
authors: Kyung-No
authors: KN
authors: Son
authors: Howard L
authors: HL
authors: Lipton
mesh_terms: D000818:Animals; D017209:Apoptosis; D018188:Cardiovirus Infections / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D016923:Cell Death; D006224:Cricetinae; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012376:Rodent Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology* / Q000821:virology; D017945:Theilovirus / Q000235:genetics / Q000502:physiology*
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2