Disruption of mitochondrial networks by the human cytomegalovirus UL37 gene product viral mitochondrion-localized inhibitor of apoptosis.
By 24 h after infection with human cytomegalovirus, the reticular mitochondrial network characteristic of uninfected fibroblasts was disrupted as mitochondria became punctate and dispersed. These alterations were associated with expression of the immediate-early (alpha) antiapoptotic UL37x1 gene product viral mitochondrion-localized inhibitor of apoptosis (vMIA). Similar alterations in mitochondrial morphology were induced directly by vMIA in transfected cells. A 68-amino-acid antiapoptotic derivative of vMIA containing the mitochondrial localization and antiapoptotic domains also induced disruption, whereas a mutant lacking the antiapoptotic domain failed to cause disruption. These data suggest that the fission and/or fusion process that normally controls mitochondrial networks is altered by vMIA. Mitochondrial fission has been implicated in the induction of apoptosis and vMIA-mediated inhibition of apoptosis may occur subsequent to this event.
McCormick
A Louise
AL
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305-5124, USA.
Smith
Vanessa L
VL
Chow
Dar
D
Mocarski
Edward S
ES
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000472:pathogenicity*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein
D017874:Immediate-Early Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C420323:UL37 protein, Human herpesvirus 5; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein