Viral modulation of programmed necrosis

William J. Kaiser, Jason W. Upton, Edward S. Mocarski

Research output: Contribution to journalReview articlepeer-review

73 Scopus citations

Abstract

Apoptosis and programmed necrosis balance each other as alternate first line host defense pathways against which viruses have evolved countermeasures. Intrinsic apoptosis, the critical programmed cell death pathway that removes excess cells during embryonic development and tissue homeostasis, follows a caspase cascade triggered at mitochondria and modulated by virus-encoded anti-apoptotic B cell leukemia (BCL)2-like suppressors. Extrinsic apoptosis controlled by caspase 8 arose during evolution to trigger executioner caspases directly, circumventing viral suppressors of intrinsic (mitochondrial) apoptosis and providing the selective pressure for viruses to acquire caspase 8 suppressors. Programmed necrosis likely evolved most recently as a 'trap door' adaptation to extrinsic apoptosis. Receptor interacting protein (RIP)3 kinase (also called RIPK3) becomes active when either caspase 8 activity or polyubiquitylation of RIP1 is compromised. This evolutionary dialog implicates caspase 8 as a 'supersensor' alternatively activating and suppressing cell death pathways.

Original languageEnglish (US)
Pages (from-to)296-306
Number of pages11
JournalCurrent Opinion in Virology
Volume3
Issue number3
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Virology

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