Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways

• Type of Material: Article
• Authors: Edward S Mocarski, Emory University; Jason W. Upton, University of Texas Austin; William Kaiser, Emory University
• Language: English
• Date: 2012-02-01
• Publisher: Nature Research (part of Springer Nature): Review Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Macmillan Publishers Limited. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/nri3131
• Title of Journal or Parent Work: Nature Reviews Immunology
• ISSN: 1474-1733
• Volume: 12
• Issue: 2
• Start Page: 79
• End Page: 88
• Grant/Funding Information: The research was supported by grants from the US National Institutes of Health (AI030363 and AI020212) and the Georgia Cancer Coalition.
• Keywords: INDUCED INFLAMMATION; PROGRAMMED NECROSIS; LYMPHOCYTE-ACTIVATION; NF-KAPPA-B; SIGNALING COMPLEX; TUMOR-NECROSIS-FACTOR; KINASE RIP; Immunology; TNF-ALPHA; CELL-DEATH; Life Sciences & Biomedicine; RECEPTOR-INTERACTING PROTEIN; Science & Technology
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

Pathogens specifically target both the caspase 8-dependent apoptotic cell death pathway and the necrotic cell death pathway that is dependent on receptor-interacting protein 1 (RIP1; also known as RIPK1) and RIP3 (also known as RIPK3). The fundamental co-regulation of these two cell death pathways emerged when the midgestational death of mice deficient in FAS-associated death domain protein (FADD) or caspase 8 was reversed by elimination of RIP1 or RIP3, indicating a far more entwined relationship than previously appreciated. Thus, mammals require caspase 8 activity during embryogenesis to suppress the kinases RIP1 and RIP3 as part of the dialogue between two distinct cell death processes that together fulfil reinforcing roles in the host defence against intracellular pathogens such as herpesviruses.