Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses

被引:183
作者
Holm, Christian K. [1 ,2 ]
Rahbek, Stine H. [1 ,2 ]
Gad, Hans Henrik [2 ,3 ]
Bak, Rasmus O. [1 ,2 ]
Jakobsen, Martin R. [1 ,2 ]
Jiang, Zhaozaho [4 ]
Hansen, Anne Louise [1 ,2 ]
Jensen, Simon K. [1 ]
Sun, Chenglong [1 ,2 ]
Thomsen, Martin K. [1 ,2 ]
Laustsen, Anders [1 ,2 ]
Nielsen, Camilla G. [1 ,2 ]
Severinsen, Kasper [5 ]
Xiong, Yingluo [1 ,6 ]
Burdette, Dara L. [7 ]
Hornung, Veit [8 ]
Lebbink, Robert Jan [9 ]
Duch, Mogens [3 ,10 ]
Fitzgerald, Katherine A. [4 ]
Bahrami, Shervin [3 ,10 ]
Mikkelsen, Jakob Giehm [1 ,2 ]
Hartmann, Rune [2 ,3 ]
Paludan, Soren R. [1 ,2 ]
机构
[1] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark
[2] Aarhus Univ, Aarhus Res Ctr Innate Immun, DK-8000 Aarhus, Denmark
[3] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark
[4] Univ Massachusetts, Dept Med, Div Infect Dis & Immunol, Amherst, MA 01003 USA
[5] Aarhus Univ Hosp, Dept Psychiat, DK-8000 Aarhus, Denmark
[6] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai 200433, Peoples R China
[7] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA
[8] Univ Bonn, Univ Hosp, Inst Mol Med, D-53127 Bonn, Germany
[9] Univ Med Ctr, Dept Med Microbiol, NL-3508 GA Utrecht, Netherlands
[10] Skauvaccines, DK-8200 Aarhus Nord, Denmark
关键词
CYCLIC DI-GMP; INNATE IMMUNITY; RIG-I; RECOGNITION; PROTEIN; ADAPTER; ACTIVATION; FUSION; SENSOR; ROLES;
D O I
10.1038/ncomms10680
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.
引用
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页数:9
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共 34 条
[1]   DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING [J].
Aguirre, Sebastian ;
Maestre, Ana M. ;
Pagni, Sarah ;
Patel, Jenish R. ;
Savage, Timothy ;
Gutman, Delia ;
Maringer, Kevin ;
Bernal-Rubio, Dabeiba ;
Shabman, Reed S. ;
Simon, Viviana ;
Rodriguez-Madoz, Juan R. ;
Mulder, Lubbertus C. F. ;
Barber, Glen N. ;
Fernandez-Sesma, Ana .
PLOS PATHOGENS, 2012, 8 (10)
[2]   Age-dependent role for CCR5 in antiviral host defense against herpes simplex virus type 2 [J].
Ank, N ;
Petersen, YJ ;
Malmgaard, L ;
Mogensen, SC ;
Paludan, SR .
JOURNAL OF VIROLOGY, 2005, 79 (15) :9831-9841
[3]   Immune suppressive activity of the influenza fusion peptide [J].
Bahrami, Shervin ;
Laska, Magdalena Janina ;
Pedersen, Finn Skou ;
Duch, Mogens .
VIRUS RESEARCH, 2016, 211 :126-132
[4]   Potent microRNA suppression by RNA Pol II-transcribed 'Tough Decoy' inhibitors [J].
Bak, Rasmus O. ;
Hollensen, Anne Kruse ;
Primo, Maria Nascimento ;
Sorensen, Camilla Darum ;
Mikkelsen, Jacob Giehm .
RNA, 2013, 19 (02) :280-293
[5]   MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus [J].
Bhoj, Vijay G. ;
Sun, Qinmiao ;
Bhoj, Elizabeth J. ;
Somers, Cynthia ;
Chen, Xiang ;
Torres, Juan-Pablo ;
Mejias, Asuncion ;
Gomez, Ana M. ;
Jafri, Hasan ;
Ramilo, Octavio ;
Chen, Zhijian J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (37) :14046-14051
[6]   Viral evasion and subversion of pattern-recognition receptor signalling [J].
Bowie, Andrew G. ;
Unterholzner, Leonie .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (12) :911-922
[7]   STING is a direct innate immune sensor of cyclic di-GMP [J].
Burdette, Dara L. ;
Monroe, Kathryn M. ;
Sotelo-Troha, Katia ;
Iwig, Jeff S. ;
Eckert, Barbara ;
Hyodo, Mamoru ;
Hayakawa, Yoshihiro ;
Vance, Russell E. .
NATURE, 2011, 478 (7370) :515-U111
[8]   Hepatitis C virus NS4B blocks the interaction of STING and TBK1 to evade host innate immunity [J].
Ding, Qiang ;
Cao, Xuezhi ;
Lu, Jie ;
Huang, Bing ;
Liu, Yong-Jun ;
Kato, Nobuyuki ;
Shu, Hong-Bing ;
Zhong, Jin .
JOURNAL OF HEPATOLOGY, 2013, 59 (01) :52-58
[9]   Influenza A Virus NS1 Targets the Ubiquitin Ligase TRIM25 to Evade Recognition by the Host Viral RNA Sensor RIG-I [J].
Gack, Michaela Ulrike ;
Albrecht, Randy Allen ;
Urano, Tomohiko ;
Inn, Kyung-Soo ;
Huang, I-Chueh ;
Carnero, Elena ;
Farzan, Michael ;
Inoue, Satoshi ;
Jung, Jae Ung ;
Garcia-Sastre, Adolfo .
CELL HOST & MICROBE, 2009, 5 (05) :439-449
[10]   Structure-Function Analysis of STING Activation by c[G(2′,5′) pA(3′,5′)p] and Targeting by Antiviral DMXAA [J].
Gao, Pu ;
Ascano, Manuel ;
Zillinger, Thomas ;
Wang, Weiyi ;
Dai, Peihong ;
Serganov, Artem A. ;
Gaffney, Barbara L. ;
Shuman, Stewart ;
Jones, Roger A. ;
Deng, Liang ;
Hartmann, Gunther ;
Barchet, Winfried ;
Tuschl, Thomas ;
Patel, Dinshaw J. .
CELL, 2013, 154 (04) :748-762