en
Scientific article
English

The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases

Published inCell death and differentiation, vol. 15, no. 11, p. 1804-1811
Publication date2008
Abstract

The outcome of a viral infection depends on the interplay between the host's capacity to trigger potent antiviral responses and viral mechanisms that counteract them. Although Toll-like receptor (TLR)-3, which recognizes virally derived double-stranded (ds) RNA, transmits downstream antiviral signaling through the TIR adaptor Trif (TICAM-1), viral RNA-sensing RIG-like helicases (RLHs) use the mitochondrial-bound CARD protein Cardif (IPS-1/MAVS/VISA). The importance of these two antiviral signaling pathways is reflected by the fact that both adaptors are inhibited through specific cleavage triggered by the hepatitis C virus serine protease NS3-4A. Here, we show that inactivation can also occur through cellular caspases activated by various pro-apoptotic signals. Upon caspase-dependent cleavage both adaptors loose their capacity to activate the transcription factors interferon regulatory factors (IRF) and NF-kappaB. Importantly, poliovirus infection triggers a caspase-dependent cleavage of Cardif, suggesting that some viruses may activate caspases not only as a mean to facilitate shedding and replication, but also to impair antiviral responses.

Keywords
  • Adaptor Proteins, Signal Transducing/metabolism
  • Adaptor Proteins, Vesicular Transport/metabolism
  • Antiviral Agents/metabolism
  • Caspases/metabolism
  • Hela Cells
  • Humans
  • Interferon Regulatory Factors/metabolism
  • Models, Biological
  • Poliovirus/physiology
  • Protein Processing, Post-Translational
Citation (ISO format)
REBSAMEN, Manuele et al. The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases. In: Cell death and differentiation, 2008, vol. 15, n° 11, p. 1804–1811. doi: 10.1038/cdd.2008.119
Main files (1)
Article (Accepted version)
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Identifiers
ISSN of the journal1350-9047
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