DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity

Qingyuan Zhu; Peng Tan; Yinyin Li; Meng Lin; Chaoran Li; Jingrong Mao; Jun Cui; Wei Zhao; Helen Y. Wang; Rong Fu Wang

doi:10.1371/journal.ppat.1006886

DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity

Qingyuan Zhu, Peng Tan, Yinyin Li, Meng Lin, Chaoran Li, Jingrong Mao, Jun Cui, Wei Zhao, Helen Y. Wang, Rong Fu Wang

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

31 Scopus citations

Abstract

Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is an RNA helicase required for the translation of 5' structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5' structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity.

Original language	English (US)
Article number	e1006886
Pages (from-to)	e1006886
Journal	PLoS pathogens
Volume	14
Issue number	2
DOIs	https://doi.org/10.1371/journal.ppat.1006886
State	Published - Feb 2018

Keywords

Animals
Cardiovirus Infections/genetics
Cells, Cultured
Cercopithecus aethiops
Encephalomyocarditis virus/genetics
HEK293 Cells
Host-Pathogen Interactions/genetics
Humans
Immunity, Innate/genetics
Interferon-Induced Helicase, IFIH1/physiology
RNA Helicases/genetics
RNA, Viral/genetics
Signal Transduction/genetics
Vero Cells

ASJC Scopus subject areas

Genetics
Molecular Biology
Virology
Parasitology
Microbiology
Immunology

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10.1371/journal.ppat.1006886

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@article{e160a79afc4140c095d3bcff2d2ec9a6,

title = "DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity",

abstract = "Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is an RNA helicase required for the translation of 5' structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5' structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity.",

keywords = "Animals, Cardiovirus Infections/genetics, Cells, Cultured, Cercopithecus aethiops, Encephalomyocarditis virus/genetics, HEK293 Cells, Host-Pathogen Interactions/genetics, Humans, Immunity, Innate/genetics, Interferon-Induced Helicase, IFIH1/physiology, RNA Helicases/genetics, RNA, Viral/genetics, Signal Transduction/genetics, Vero Cells",

author = "Qingyuan Zhu and Peng Tan and Yinyin Li and Meng Lin and Chaoran Li and Jingrong Mao and Jun Cui and Wei Zhao and Wang, {Helen Y.} and Wang, {Rong Fu}",

note = "Funding Information: This work was supported in part by grants from the National Institutes of Health (R01CA09327, https://www.nih.gov/), Cancer Prevention and Research Institute of Texas (RP170537, http://www.cprit.state.tx.us/), Department of Defense (DoD) Breast Cancer Research Program (BCRP) (W81XWH-16-1-0417, http://cdmrp.army.mil/bcrp/) and Golfer against cancer foundation to RFW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Drs. Qingtian Li, Yanxia Song and Bo Ning for technical assistance. We thank Dr. Shizuo Akira (Osaka University) for the MDA5 knockout MEF cells. Publisher Copyright: {\textcopyright} 2018 Zhu et al.",

year = "2018",

month = feb,

doi = "10.1371/journal.ppat.1006886",

language = "English (US)",

volume = "14",

pages = "e1006886",

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issn = "1553-7366",

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T1 - DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity

AU - Zhu, Qingyuan

AU - Tan, Peng

AU - Li, Yinyin

AU - Lin, Meng

AU - Li, Chaoran

AU - Mao, Jingrong

AU - Cui, Jun

AU - Zhao, Wei

AU - Wang, Helen Y.

AU - Wang, Rong Fu

N1 - Funding Information: This work was supported in part by grants from the National Institutes of Health (R01CA09327, https://www.nih.gov/), Cancer Prevention and Research Institute of Texas (RP170537, http://www.cprit.state.tx.us/), Department of Defense (DoD) Breast Cancer Research Program (BCRP) (W81XWH-16-1-0417, http://cdmrp.army.mil/bcrp/) and Golfer against cancer foundation to RFW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Drs. Qingtian Li, Yanxia Song and Bo Ning for technical assistance. We thank Dr. Shizuo Akira (Osaka University) for the MDA5 knockout MEF cells. Publisher Copyright: © 2018 Zhu et al.

PY - 2018/2

Y1 - 2018/2

N2 - Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is an RNA helicase required for the translation of 5' structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5' structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity.

AB - Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is an RNA helicase required for the translation of 5' structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5' structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity.

KW - Animals

KW - Cardiovirus Infections/genetics

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KW - Humans

KW - Immunity, Innate/genetics

KW - Interferon-Induced Helicase, IFIH1/physiology

KW - RNA Helicases/genetics

KW - RNA, Viral/genetics

KW - Signal Transduction/genetics

KW - Vero Cells

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SN - 1553-7366

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JF - PLoS pathogens

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ER -

DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity

Abstract

Keywords

ASJC Scopus subject areas

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