@article{2958c19aeee4447e8ae4131c9cd69e0e,
title = "RIPK3 Activates Parallel Pathways of MLKL-Driven Necroptosis and FADD-Mediated Apoptosis to Protect against Influenza A Virus",
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.",
author = "Shoko Nogusa and Thapa, {Roshan J.} and Dillon, {Christopher P.} and Swantje Liedmann and Oguin, {Thomas H.} and Ingram, {Justin P.} and Rodriguez, {Diego A.} and Rachelle Kosoff and Shalini Sharma and Oliver Sturm and Katherine Verbist and Gough, {Peter J.} and John Bertin and Hartmann, {Boris M.} and Sealfon, {Stuart C.} and Kaiser, {William J.} and Mocarski, {Edward S.} and L{\'o}pez, {Carolina B.} and Thomas, {Paul G.} and Andrew Oberst and Green, {Douglas R.} and Siddharth Balachandran",
note = "Funding Information: We are grateful to Vishva Dixit, Adolfo Garcia-Sastre, Scott Hensley, Ganes Sen, and Luis Sigal for viruses, cells, and mice. This work was supported by NIAID contract HHSN272201400006C (St. Jude Center of Excellence for Influenza Research and Surveillance) to P.G.T., NIH grant AI109472 to C.B.L., NIH grants AI44828 and CA169291 to D.R.G., and NIH grants CA168621, CA190542, and AI113469 to S.B. Additional funds were provided by the F.M. Kirby Foundation, and via NIH Cancer Center Support Grant P30CA006927 to S.B. P.J.G. and J.B. are employees of GlaxoSmithKline. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jul,
day = "13",
doi = "10.1016/j.chom.2016.05.011",
language = "English (US)",
volume = "20",
pages = "13--24",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "1",
}