PMID- 15353550 OWN - NLM STAT- MEDLINE DCOM- 20041025 LR - 20181113 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 166 IP - 6 DP - 2004 Sep 13 TI - A novel checkpoint in the Bcl-2-regulated apoptotic pathway revealed by murine cytomegalovirus infection of dendritic cells. PG - 827-37 AB - Infection with murine cytomegalovirus (MCMV) has contributed to understanding many aspects of human infection and, additionally, has provided important insight to understanding complex cellular responses. Dendritic cells (DCs) are a major target for MCMV infection. Here, we analyze the effects of MCMV infection on DC viability, and show that infected DCs become resistant to apoptosis induced by growth factor deprivation. The precise contribution of changes in the expression of Bcl-2 family proteins has been assessed and a new checkpoint in the apoptotic pathway identified. Despite their resistance to apoptosis, MCMV-infected DCs showed Bax to be tightly associated with mitochondria and, together with Bak, forming high molecular weight oligomers, changes normally associated with apoptotic cell death. Exposure of a constitutively occluded Bax NH2-terminal epitope was blocked after infection. These results suggest that MCMV has evolved a novel strategy for inhibiting apoptosis and provide evidence that apoptosis can be regulated after translocation, integration, and oligomerization of Bax at the mitochondrial membrane. FAU - Andoniou, Christopher E AU - Andoniou CE AD - Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Western Australia 6009, Australia. FAU - Andrews, Daniel M AU - Andrews DM FAU - Manzur, Mitali AU - Manzur M FAU - Ricciardi-Castagnoli, Paola AU - Ricciardi-Castagnoli P FAU - Degli-Esposti, Mariapia A AU - Degli-Esposti MA LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040907 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Bak1 protein, mouse) RN - 0 (Bax protein, mouse) RN - 0 (Culture Media, Conditioned) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-2 Homologous Antagonist-Killer Protein) RN - 0 (bcl-2-Associated X Protein) SB - IM MH - Animals MH - Apoptosis/*genetics MH - Cell Line MH - Cell Line, Transformed MH - Cell Survival MH - Cell Transformation, Viral MH - Culture Media, Conditioned MH - Dendritic Cells/*metabolism MH - Gene Expression Regulation MH - Herpesviridae Infections/*virology MH - Intracellular Membranes/physiology MH - Membrane Potentials MH - Membrane Proteins/metabolism MH - Mice MH - Mitochondria/physiology MH - Muromegalovirus/*physiology MH - Proto-Oncogene Proteins/metabolism MH - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism MH - bcl-2 Homologous Antagonist-Killer Protein MH - bcl-2-Associated X Protein PMC - PMC2172116 EDAT- 2004/09/09 05:00 MHDA- 2004/10/27 09:00 PMCR- 2005/03/13 CRDT- 2004/09/09 05:00 PHST- 2004/09/09 05:00 [pubmed] PHST- 2004/10/27 09:00 [medline] PHST- 2004/09/09 05:00 [entrez] PHST- 2005/03/13 00:00 [pmc-release] AID - jcb.200403010 [pii] AID - 200403010 [pii] AID - 10.1083/jcb.200403010 [doi] PST - ppublish SO - J Cell Biol. 2004 Sep 13;166(6):827-37. doi: 10.1083/jcb.200403010. Epub 2004 Sep 7.