| Literature DB >> 27321907 |
Shoko Nogusa1, Roshan J Thapa1, Christopher P Dillon2, Swantje Liedmann2, Thomas H Oguin2, Justin P Ingram1, Diego A Rodriguez2, Rachelle Kosoff1, Shalini Sharma2, Oliver Sturm2, Katherine Verbist2, Peter J Gough3, John Bertin3, Boris M Hartmann4, Stuart C Sealfon4, William J Kaiser5, Edward S Mocarski5, Carolina B López6, Paul G Thomas2, Andrew Oberst7, Douglas R Green8, Siddharth Balachandran9.
Abstract
Influenza A virus (IAV) is a lytic virus in primary cultures of many cell types and in vivo. We report that the kinase RIPK3 is essential for IAV-induced lysis of mammalian fibroblasts and lung epithelial cells. Replicating IAV drives assembly of a RIPK3-containing complex that includes the kinase RIPK1, the pseudokinase MLKL, and the adaptor protein FADD, and forms independently of signaling by RNA-sensing innate immune receptors (RLRs, TLRs, PKR), or the cytokines type I interferons and TNF-α. Downstream of RIPK3, IAV activates parallel pathways of MLKL-driven necroptosis and FADD-mediated apoptosis, with the former reliant on RIPK3 kinase activity and neither on RIPK1 activity. Mice deficient in RIPK3 or doubly deficient in MLKL and FADD, but not MLKL alone, are more susceptible to IAV than their wild-type counterparts, revealing an important role for RIPK3-mediated apoptosis in antiviral immunity. Collectively, these results outline RIPK3-activated cytolytic mechanisms essential for controlling respiratory IAV infection.Entities:
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Year: 2016 PMID： 27321907 PMCID： PMC5026823 DOI： 10.1016/j.chom.2016.05.011
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023