DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death

Roshan J. Thapa; Justin P. Ingram; Katherine B. Ragan; Shoko Nogusa; David F. Boyd; Asiel A. Benitez; Haripriya Sridharan; Rachelle Kosoff; Maria Shubina; Vanessa J. Landsteiner; Mark Andrake; Peter Vogel; Luis J. Sigal; Benjamin R. tenOever; Paul G. Thomas; Jason W. Upton; Siddharth Balachandran

doi:10.1016/j.chom.2016.09.014

DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death

Roshan J. Thapa, Justin P. Ingram, Katherine B. Ragan, Shoko Nogusa, David F. Boyd, Asiel A. Benitez, Haripriya Sridharan, Rachelle Kosoff, Maria Shubina, Vanessa J. Landsteiner, Mark Andrake, Peter Vogel, Luis J. Sigal, Benjamin R. tenOever, Paul G. Thomas, Jason W. Upton, Siddharth Balachandran

Research output: Contribution to journal › Article › peer-review

306 Scopus citations

Abstract

Influenza A virus (IAV) is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the host kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. How IAV activates RIPK3 remains unknown. We report that DAI (ZBP1/DLM-1), previously implicated as a cytoplasmic DNA sensor, is essential for RIPK3 activation by IAV. Upon infection, DAI recognizes IAV genomic RNA, associates with RIPK3, and is required for recruitment of MLKL and RIPK1 to RIPK3. Cells lacking DAI or containing DAI mutants deficient in nucleic acid binding are resistant to IAV-triggered necroptosis and apoptosis. DAI-deficient mice fail to control IAV replication and succumb to lethal respiratory infection. These results identify DAI as a link between IAV replication and RIPK3 activation and implicate DAI as a sensor of RNA viruses.

Original language	English
Pages (from-to)	674-681
Number of pages	8
Journal	Cell Host and Microbe
Volume	20
Issue number	5
DOIs	https://doi.org/10.1016/j.chom.2016.09.014
State	Published - 9 Nov 2016

Access to Document

10.1016/j.chom.2016.09.014

Cite this

Thapa, R. J., Ingram, J. P., Ragan, K. B., Nogusa, S., Boyd, D. F., Benitez, A. A., Sridharan, H., Kosoff, R., Shubina, M., Landsteiner, V. J., Andrake, M., Vogel, P., Sigal, L. J., tenOever, B. R., Thomas, P. G., Upton, J. W., & Balachandran, S. (2016). DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death. Cell Host and Microbe, 20(5), 674-681. https://doi.org/10.1016/j.chom.2016.09.014

@article{69e7ca604fb046ae83666f3b0ed50bc8,

title = "DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death",

abstract = "Influenza A virus (IAV) is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the host kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. How IAV activates RIPK3 remains unknown. We report that DAI (ZBP1/DLM-1), previously implicated as a cytoplasmic DNA sensor, is essential for RIPK3 activation by IAV. Upon infection, DAI recognizes IAV genomic RNA, associates with RIPK3, and is required for recruitment of MLKL and RIPK1 to RIPK3. Cells lacking DAI or containing DAI mutants deficient in nucleic acid binding are resistant to IAV-triggered necroptosis and apoptosis. DAI-deficient mice fail to control IAV replication and succumb to lethal respiratory infection. These results identify DAI as a link between IAV replication and RIPK3 activation and implicate DAI as a sensor of RNA viruses.",

author = "Thapa, {Roshan J.} and Ingram, {Justin P.} and Ragan, {Katherine B.} and Shoko Nogusa and Boyd, {David F.} and Benitez, {Asiel A.} and Haripriya Sridharan and Rachelle Kosoff and Maria Shubina and Landsteiner, {Vanessa J.} and Mark Andrake and Peter Vogel and Sigal, {Luis J.} and tenOever, {Benjamin R.} and Thomas, {Paul G.} and Upton, {Jason W.} and Siddharth Balachandran",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = nov,

day = "9",

doi = "10.1016/j.chom.2016.09.014",

language = "English",

volume = "20",

pages = "674--681",

journal = "Cell Host and Microbe",

issn = "1931-3128",

publisher = "Cell Press",

number = "5",

}

Thapa, RJ, Ingram, JP, Ragan, KB, Nogusa, S, Boyd, DF, Benitez, AA, Sridharan, H, Kosoff, R, Shubina, M, Landsteiner, VJ, Andrake, M, Vogel, P, Sigal, LJ, tenOever, BR, Thomas, PG, Upton, JW & Balachandran, S 2016, 'DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death', Cell Host and Microbe, vol. 20, no. 5, pp. 674-681. https://doi.org/10.1016/j.chom.2016.09.014

TY - JOUR

T1 - DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death

AU - Thapa, Roshan J.

AU - Ingram, Justin P.

AU - Ragan, Katherine B.

AU - Nogusa, Shoko

AU - Boyd, David F.

AU - Benitez, Asiel A.

AU - Sridharan, Haripriya

AU - Kosoff, Rachelle

AU - Shubina, Maria

AU - Landsteiner, Vanessa J.

AU - Andrake, Mark

AU - Vogel, Peter

AU - Sigal, Luis J.

AU - tenOever, Benjamin R.

AU - Thomas, Paul G.

AU - Upton, Jason W.

AU - Balachandran, Siddharth

PY - 2016/11/9

Y1 - 2016/11/9

N2 - Influenza A virus (IAV) is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the host kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. How IAV activates RIPK3 remains unknown. We report that DAI (ZBP1/DLM-1), previously implicated as a cytoplasmic DNA sensor, is essential for RIPK3 activation by IAV. Upon infection, DAI recognizes IAV genomic RNA, associates with RIPK3, and is required for recruitment of MLKL and RIPK1 to RIPK3. Cells lacking DAI or containing DAI mutants deficient in nucleic acid binding are resistant to IAV-triggered necroptosis and apoptosis. DAI-deficient mice fail to control IAV replication and succumb to lethal respiratory infection. These results identify DAI as a link between IAV replication and RIPK3 activation and implicate DAI as a sensor of RNA viruses.

AB - Influenza A virus (IAV) is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the host kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. How IAV activates RIPK3 remains unknown. We report that DAI (ZBP1/DLM-1), previously implicated as a cytoplasmic DNA sensor, is essential for RIPK3 activation by IAV. Upon infection, DAI recognizes IAV genomic RNA, associates with RIPK3, and is required for recruitment of MLKL and RIPK1 to RIPK3. Cells lacking DAI or containing DAI mutants deficient in nucleic acid binding are resistant to IAV-triggered necroptosis and apoptosis. DAI-deficient mice fail to control IAV replication and succumb to lethal respiratory infection. These results identify DAI as a link between IAV replication and RIPK3 activation and implicate DAI as a sensor of RNA viruses.

UR - http://www.scopus.com/inward/record.url?scp=84994731750&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2016.09.014

DO - 10.1016/j.chom.2016.09.014

M3 - Article

C2 - 27746097

AN - SCOPUS:84994731750

SN - 1931-3128

VL - 20

SP - 674

EP - 681

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 5

ER -

DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death

Abstract

Access to Document

Fingerprint

Cite this