DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVS
DExD/H-box helicases play essential roles in RNA metabolism, and emerging data suggests that they have additional functions in antiviral immunity across species. However, little is known about this evolutionarily conserved family in antiviral responses in lower species. Here, through isolation of po...
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Language: | English |
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Frontiers Media S.A.
2019-09-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02202/full |
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doaj-770cf00874e34f1b9988c79a03c2f11c |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jie Ruan Yange Cao Tao Ling Peiyi Li Shengpeng Wu Dezhi Peng Yao Wang Xin Jia Shangwu Chen Anlong Xu Anlong Xu Shaochun Yuan Shaochun Yuan |
spellingShingle |
Jie Ruan Yange Cao Tao Ling Peiyi Li Shengpeng Wu Dezhi Peng Yao Wang Xin Jia Shangwu Chen Anlong Xu Anlong Xu Shaochun Yuan Shaochun Yuan DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVS Frontiers in Immunology amphioxus (lancelet) innate antiviral immunity dsRNA sensors RNA Helicases DDX23 |
author_facet |
Jie Ruan Yange Cao Tao Ling Peiyi Li Shengpeng Wu Dezhi Peng Yao Wang Xin Jia Shangwu Chen Anlong Xu Anlong Xu Shaochun Yuan Shaochun Yuan |
author_sort |
Jie Ruan |
title |
DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVS |
title_short |
DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVS |
title_full |
DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVS |
title_fullStr |
DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVS |
title_full_unstemmed |
DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVS |
title_sort |
ddx23, an evolutionary conserved dsrna sensor, participates in innate antiviral responses by pairing with trif or mavs |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-09-01 |
description |
DExD/H-box helicases play essential roles in RNA metabolism, and emerging data suggests that they have additional functions in antiviral immunity across species. However, little is known about this evolutionarily conserved family in antiviral responses in lower species. Here, through isolation of poly(I:C)-binding proteins in amphioxus, an extant basal chordate, we found that DExD/H-box helicases DHX9, DHX15, and DDX23 are responsible for cytoplasmic dsRNA detection in amphioxus. Since the antiviral roles of DDX23 have not been characterized in mammals, we performed further poly(I:C) pull-down assays and found that human DDX23 binds to LMW poly(I:C) through its N-terminal region, suggesting that DDX23 is an evolutionarily conserved dsRNA sensor. Knockdown of human DDX23 enhanced the replication of VSV and reduced the activation of the NF-κB and IRF3. Moreover, when stimulated with poly(I:C) or VSV, human DDX23 translocated from the nucleus to the cytoplasm and formed complexes with TRIF or MAVS to initiate downstream signaling. Collectively, this comparative immunological study not only defined DDX23 as an emerging nuclear pattern recognition receptor (PRR) for the innate sensing of an RNA virus, but also extended the essential role of the DExD/H helicase family in viral RNA sensing from mammals to basal chordates. |
topic |
amphioxus (lancelet) innate antiviral immunity dsRNA sensors RNA Helicases DDX23 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02202/full |
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doaj-770cf00874e34f1b9988c79a03c2f11c2020-11-25T02:11:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02202477730DDX23, an Evolutionary Conserved dsRNA Sensor, Participates in Innate Antiviral Responses by Pairing With TRIF or MAVSJie Ruan0Yange Cao1Tao Ling2Peiyi Li3Shengpeng Wu4Dezhi Peng5Yao Wang6Xin Jia7Shangwu Chen8Anlong Xu9Anlong Xu10Shaochun Yuan11Shaochun Yuan12State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaState Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaLaboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, ChinaDExD/H-box helicases play essential roles in RNA metabolism, and emerging data suggests that they have additional functions in antiviral immunity across species. However, little is known about this evolutionarily conserved family in antiviral responses in lower species. Here, through isolation of poly(I:C)-binding proteins in amphioxus, an extant basal chordate, we found that DExD/H-box helicases DHX9, DHX15, and DDX23 are responsible for cytoplasmic dsRNA detection in amphioxus. Since the antiviral roles of DDX23 have not been characterized in mammals, we performed further poly(I:C) pull-down assays and found that human DDX23 binds to LMW poly(I:C) through its N-terminal region, suggesting that DDX23 is an evolutionarily conserved dsRNA sensor. Knockdown of human DDX23 enhanced the replication of VSV and reduced the activation of the NF-κB and IRF3. Moreover, when stimulated with poly(I:C) or VSV, human DDX23 translocated from the nucleus to the cytoplasm and formed complexes with TRIF or MAVS to initiate downstream signaling. Collectively, this comparative immunological study not only defined DDX23 as an emerging nuclear pattern recognition receptor (PRR) for the innate sensing of an RNA virus, but also extended the essential role of the DExD/H helicase family in viral RNA sensing from mammals to basal chordates.https://www.frontiersin.org/article/10.3389/fimmu.2019.02202/fullamphioxus (lancelet)innate antiviral immunitydsRNA sensorsRNA HelicasesDDX23 |