title: Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors.
abstract: Viruses have evolved many distinct strategies to avoid the host's apoptotic response. Here we describe a new family of viral inhibitors (v-FLIPs) which interfere with apoptosis signalled through death receptors and which are present in several gamma-herpesviruses (including Kaposi's-sarcoma-associated human herpesvirus-8), as well as in the tumorigenic human molluscipoxvirus. v-FLIPs contain two death-effector domains which interact with the adaptor protein FADD, and this inhibits the recruitment and activation of the protease FLICE by the CD95 death receptor. Cells expressing v-FLIPs are protected against apoptosis induced by CD95 or by the related death receptors TRAMP and TRAIL-R. The herpesvirus saimiri FLIP is detected late during the lytic viral replication cycle, at a time when host cells are partially protected from CD95-ligand-mediated apoptosis. Protection of virus-infected cells against death-receptor-induced apoptosis may lead to higher virus production and contribute to the persistence and oncogenicity of several FLIP-encoding viruses.
authors.affiliation: Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Thome
authors.forename: P
authors.initials: P
authors.lastname: Schneider
authors.forename: K
authors.initials: K
authors.lastname: Hofmann
authors.forename: H
authors.initials: H
authors.lastname: Fickenscher
authors.forename: E
authors.initials: E
authors.lastname: Meinl
authors.forename: F
authors.initials: F
authors.lastname: Neipel
authors.forename: C
authors.initials: C
authors.lastname: Mattmann
authors.forename: K
authors.initials: K
authors.lastname: Burns
authors.forename: J L
authors.initials: JL
authors.lastname: Bodmer
authors.forename: M
authors.initials: M
authors.lastname: Schröter
authors.forename: C
authors.initials: C
authors.lastname: Scaffidi
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
authors.forename: M E
authors.initials: ME
authors.lastname: Peter
authors.forename: J
authors.initials: J
authors.lastname: Tschopp
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D002460:Cell Line; D002472:Cell Transformation, Viral; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein; D018142:Gammaherpesvirinae / Q000235:genetics / Q000502:physiology*; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053219:Receptors, Tumor Necrosis Factor, Member 25; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication; D019014:fas Receptor / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053221:TNF-Related Apoptosis-Inducing Ligand; C506033:TNFRSF25 protein, human; C505653:TNFSF10 protein, human; C506034:Tnfrsf25 protein, mouse; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases