Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors

Margot Thome, Pascal Schneider, Kay Hofmann, Helmut Fickenscher, Edgar Meinl, Frank Neipel, Chantal Mattmann, Kim Burns, Jean Luc Bodmer, Michael Schröter, Carsten Scaffidi, Peter H. Krammer, Marcus E. Peter, Jürg Tschopp*

*Corresponding author for this work

Research output: Contribution to journalArticle

1063 Scopus citations

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 γ-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.

Original languageEnglish (US)
Pages (from-to)517-521
Number of pages5
JournalNature
Volume386
Issue number6624
DOIs
StatePublished - Apr 3 1997

ASJC Scopus subject areas

  • General

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    Thome, M., Schneider, P., Hofmann, K., Fickenscher, H., Meinl, E., Neipel, F., Mattmann, C., Burns, K., Bodmer, J. L., Schröter, M., Scaffidi, C., Krammer, P. H., Peter, M. E., & Tschopp, J. (1997). Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature, 386(6624), 517-521. https://doi.org/10.1038/386517a0