title: A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2.
abstract: Human cytomegalovirus (CMV), a herpesvirus that causes congenital disease and opportunistic infections in immunocompromised individuals, encodes functions that facilitate efficient viral propagation by altering host cell behavior. Here we show that CMV blocks apoptosis mediated by death receptors and encodes a mitochondria-localized inhibitor of apoptosis, denoted vMIA, capable of suppressing apoptosis induced by diverse stimuli. vMIA, a product of the viral UL37 gene, inhibits Fas-mediated apoptosis at a point downstream of caspase-8 activation and Bid cleavage but upstream of cytochrome c release, while residing in mitochondria and associating with adenine nucleotide translocator. These functional properties resemble those ascribed to Bcl-2; however, the absence of sequence similarity to Bcl-2 or any other known cell death suppressors suggests that vMIA defines a previously undescribed class of anti-apoptotic proteins.
authors.affiliation: Apoptosis Technology, Inc., 148 Sidney Street, Cambridge, MA 02139, USA. victor.goldmacher@immunogen.com
authors.forename: V S
authors.initials: VS
authors.lastname: Goldmacher
authors.forename: L M
authors.initials: LM
authors.lastname: Bartle
authors.forename: A
authors.initials: A
authors.lastname: Skaletskaya
authors.forename: C A
authors.initials: CA
authors.lastname: Dionne
authors.forename: N L
authors.initials: NL
authors.lastname: Kedersha
authors.forename: C A
authors.initials: CA
authors.lastname: Vater
authors.forename: J W
authors.initials: JW
authors.lastname: Han
authors.forename: R J
authors.initials: RJ
authors.lastname: Lutz
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: E D
authors.initials: ED
authors.lastname: Cahir McFarland
authors.forename: E D
authors.initials: ED
authors.lastname: Kieff
authors.forename: E S
authors.initials: ES
authors.lastname: Mocarski
authors.forename: T
authors.initials: T
authors.lastname: Chittenden
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D015678:Viral Structural Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: C084763:UL37 protein, Human herpesvirus 1; D015678:Viral Structural Proteins