title: Viral modulators of cell death provide new links to old pathways.
abstract: By observing how viruses facilitate their parasitic relationships with host cells, we gain insights into key regulatory pathways of the cell. Not only are mitochondria key players in the regulation of programmed cell death, but many viral regulators of cell death also alter mitochondrial functions either directly or indirectly. Although cytomegalovirus vMIA and Epstein-Barr virus BHRF1 seem to have opposite effects on mitochondrial morphology, they both inhibit cell death. Drosophila Reaper, a regulator of developmental cell death, acts on IAP (inhibitor of apoptosis) proteins to activate caspases, but can regulate mitochondrial permeability in vitro. Despite its pivotal role in Drosophila, homologues of Reaper in other species were not previously known. Recently, amino acid sequence similarity was recognized between Drosophila Reaper and a protein known to be important for the replication and virulence of mosquito-borne bunyaviruses that cause human encephalitis. Thus, viral mechanisms for regulating apoptosis are diverse and not fully elucidated but promise to provide new insights.
authors.affiliation: Department of Molecular Microbiology, Johns Hopkins Schools of Medicine and Public Health, 615 North Wolfe St, Baltimore, Maryland 21205, USA. pirusta@jhsph.edu
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Irusta
authors.forename: Ying-bei
authors.initials: YB
authors.lastname: Chen
authors.forename: J Marie
authors.initials: JM
authors.lastname: Hardwick
mesh_terms: D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D016923:Cell Death; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D016851:Orthobunyavirus / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism / Q000502:physiology; D014981:Xenopus
chemical_list: C083278:BHRF1 protein, Human herpesvirus 4; D029721:Drosophila Proteins; D017874:Immediate-Early Proteins; C420323:UL37 protein, Human herpesvirus 5; D014764:Viral Proteins; C086973:rpr protein, Drosophila