Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling

被引:64
作者
Ban, Junsu [1 ]
Lee, Na-Rae [1 ]
Lee, Noh-Jin [1 ]
Lee, Jong Kil [1 ]
Quan, Fu-Shi [2 ]
Inn, Kyung-Soo [1 ]
机构
[1] Kyung Hee Univ, Grad Sch, Dept Fundamental Pharmaceut Sci, 26 Kyungheedae Ro, Seoul 130701, South Korea
[2] Kyung Hee Univ, Sch Med, Dept Med Zool, 26 Kyungheedae Ro, Seoul 130701, South Korea
来源
VIRUSES-BASEL | 2018年 / 10卷 / 12期
基金
新加坡国家研究基金会;
关键词
respiratory syncytial virus; nonstructural protein 1; RIG-I; TRIM25; interferon; RECOGNITION; REPLICATION; INHIBITION; LIGASE;
D O I
10.3390/v10120716
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling.
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页数:12
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共 24 条
[1]   Pathogen recognition and innate immunity [J].
Akira, S ;
Uematsu, S ;
Takeuchi, O .
CELL, 2006, 124 (04) :783-801
[2]   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
[3]   Respiratory Syncytial Virus NS1 Protein Colocalizes with Mitochondrial Antiviral Signaling Protein MAVS following Infection [J].
Boyapalle, Sandhya ;
Wong, Terianne ;
Garay, Julio ;
Teng, Michael ;
San Juan-Vergara, Homero ;
Mohapatra, Subhra ;
Mohapatra, Shyam .
PLOS ONE, 2012, 7 (02)
[4]   Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity [J].
Canedo-Marroquin, Gisela ;
Acevedo-Acevedo, Orlando ;
Rey-Jurado, Emma ;
Saavedra, Juan M. ;
Lay, Margarita K. ;
Bueno, Susan M. ;
Riedel, Claudia A. ;
Kalergis, Alexis M. .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2017, 7
[5]   MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors [J].
Castanier, Celine ;
Zemirli, Naima ;
Portier, Alain ;
Garcin, Dominique ;
Bidere, Nicolas ;
Vazquez, Aime ;
Arnoult, Damien .
BMC BIOLOGY, 2012, 10
[6]   A novel p38 mitogen activated protein kinase (MAPK) specific inhibitor suppresses respiratory syncytial virus and influenza A virus replication by inhibiting virus-induced p38 MAPK activation [J].
Choi, Myung-Soo ;
Heo, Jinyuk ;
Yi, Chae-Min ;
Ban, Junsu ;
Lee, Noh-Jin ;
Lee, Na-Rae ;
Kim, Sang Won ;
Kim, Nam-Jung ;
Inn, Kyung-Soo .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2016, 477 (03) :311-316
[7]   Roles of RIG-1 N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction [J].
Gack, Michaela U. ;
Kirchhofer, Axel ;
Shin, Young C. ;
Inn, Kyung-Soo ;
Liang, Chengyu ;
Cui, Sheng ;
Myong, Sua ;
Ha, Taekjip ;
Hopfner, Karl-Peter ;
Jung, Jae U. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (43) :16743-16748
[8]   TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity [J].
Gack, Michaela U. ;
Shin, Young C. ;
Joo, Chul-Hyun ;
Urano, Tomohiko ;
Liang, Chengyu ;
Sun, Lijun ;
Takeuchi, Osamu ;
Akira, Shizuo ;
Chen, Zhijian ;
Inoue, Satoshi ;
Jung, Jae U. .
NATURE, 2007, 446 (7138) :916-U2
[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]   Viral degradasome hijacks mitochondria to suppress innate immunity [J].
Goswami, Ramansu ;
Majumdar, Tanmay ;
Dhar, Jayeeta ;
Chattopadhyay, Saurabh ;
Bandyopadhyay, Sudip K. ;
Verbovetskaya, Valentina ;
Sen, Ganes C. ;
Barik, Sailen .
CELL RESEARCH, 2013, 23 (08) :1025-1042