Open AccessA cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2
Author(s) -
Victor S. Goldmacher,
Laura M. Bartle,
Anna Skaletskaya,
Cheryl A. Dionne,
Nancy Kedersha,
Carol A. Vater,
Jiawen Han,
Robert J. Lutz,
Shinya Watanabe,
Ellen D. Cahir McFarland,
Elliott Kieff,
Edward S. Mocarski,
Thomas Chittenden
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.22.12536
Subject(s) - adenine nucleotide translocator , apoptosis , mitochondrion , biology , cytochrome c , programmed cell death , microbiology and biotechnology , bcl 2 family , fas receptor , gene , virology , genetics
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 cytochromec 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.