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

Cell Death Differ. 2008 Nov;15(11):1804-11. doi: 10.1038/cdd.2008.119. Epub 2008 Aug 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Antiviral Agents
  • Interferon Regulatory Factors
  • TICAM1 protein, human
  • VISA protein, human
  • Caspases