Viral FLICE-inhibitory Proteins (FLIPs) Prevent Apoptosis Induced by Death Receptors

Nature. 1997 Apr 3;386(6624):517-21. doi: 10.1038/386517a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Carrier Proteins / metabolism
  • Caspase 8
  • Caspase 9
  • Caspases*
  • Cell Line
  • Cell Transformation, Viral
  • Cysteine Endopeptidases / metabolism*
  • Fas-Associated Death Domain Protein
  • Gammaherpesvirinae / genetics
  • Gammaherpesvirinae / physiology*
  • Herpesvirus 2, Saimiriine / physiology
  • Humans
  • Membrane Glycoproteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Member 25
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Proteins / physiology*
  • Virus Replication
  • fas Receptor / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • FADD protein, human
  • Fadd protein, mouse
  • Fas-Associated Death Domain Protein
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 25
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF25 protein, human
  • TNFSF10 protein, human
  • Tnfrsf25 protein, mouse
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • fas Receptor
  • CASP8 protein, human
  • CASP9 protein, human
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cysteine Endopeptidases

Associated data

  • GENBANK/U93872