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Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication

Seneca Valley virus (SVV), a non-enveloped positive single-stranded virus can cause vesicular disease in swine. However, the mechanisms by which SVV activates an innate immune response remain unknown. Mitofusin-2 (MFN2), a mitochondria-shaping protein regulating mitochondrial fusion and fission, pla...

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Autores principales: Deng, HuiDan, Zhu, Song, Zhu, Ling, Sun, Jing, Ding, YuChun, Li, FengQin, Jian, ZhiJie, Zhao, Jun, Deng, LiShuang, Deng, JunLiang, Deng, YouTian, Guo, HongRui, Sun, XianGang, Lai, Si Yuan, Tang, HuaQiao, Cui, HengMin, Ge, Liang Peng, Xu, ZhiWen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359100/
https://www.ncbi.nlm.nih.gov/pubmed/35958608
http://dx.doi.org/10.3389/fimmu.2022.955671
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author Deng, HuiDan
Zhu, Song
Zhu, Ling
Sun, Jing
Ding, YuChun
Li, FengQin
Jian, ZhiJie
Zhao, Jun
Deng, LiShuang
Deng, JunLiang
Deng, YouTian
Guo, HongRui
Sun, XianGang
Lai, Si Yuan
Tang, HuaQiao
Cui, HengMin
Ge, Liang Peng
Xu, ZhiWen
author_facet Deng, HuiDan
Zhu, Song
Zhu, Ling
Sun, Jing
Ding, YuChun
Li, FengQin
Jian, ZhiJie
Zhao, Jun
Deng, LiShuang
Deng, JunLiang
Deng, YouTian
Guo, HongRui
Sun, XianGang
Lai, Si Yuan
Tang, HuaQiao
Cui, HengMin
Ge, Liang Peng
Xu, ZhiWen
author_sort Deng, HuiDan
collection PubMed
description Seneca Valley virus (SVV), a non-enveloped positive single-stranded virus can cause vesicular disease in swine. However, the mechanisms by which SVV activates an innate immune response remain unknown. Mitofusin-2 (MFN2), a mitochondria-shaping protein regulating mitochondrial fusion and fission, plays a crucial role in innate immune responses. But, the roles of Mfn2 in SVV infection have not been elucidated. Here, we show that SVV inhibited Mfn2 expression and NLRP3 inflammasome, activating RIG-I/IRF7 signaling pathway to increase IFN-λ3 expression. Overexpression of Mfn2 inhibited RIG-I/IRF7 signaling pathway, thus decreasing IFN-λ3 expression and promoting SVV replication. Interestingly, overexpression of Mfn2 also activated NLRP3 inflammasome but did not inhibit SVV proliferation. That may mean the RIG-I/IRF7 signaling pathway plays a more important role in SVV proliferation in PK-15 cells. This study could provide important insights into the modulation of host metabolism during SVV infection and provide a strong theoretical basis for a better understanding of the pathogenic mechanism and immune activation mechanism of SVV.
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spelling pubmed-93591002022-08-10 Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication Deng, HuiDan Zhu, Song Zhu, Ling Sun, Jing Ding, YuChun Li, FengQin Jian, ZhiJie Zhao, Jun Deng, LiShuang Deng, JunLiang Deng, YouTian Guo, HongRui Sun, XianGang Lai, Si Yuan Tang, HuaQiao Cui, HengMin Ge, Liang Peng Xu, ZhiWen Front Immunol Immunology Seneca Valley virus (SVV), a non-enveloped positive single-stranded virus can cause vesicular disease in swine. However, the mechanisms by which SVV activates an innate immune response remain unknown. Mitofusin-2 (MFN2), a mitochondria-shaping protein regulating mitochondrial fusion and fission, plays a crucial role in innate immune responses. But, the roles of Mfn2 in SVV infection have not been elucidated. Here, we show that SVV inhibited Mfn2 expression and NLRP3 inflammasome, activating RIG-I/IRF7 signaling pathway to increase IFN-λ3 expression. Overexpression of Mfn2 inhibited RIG-I/IRF7 signaling pathway, thus decreasing IFN-λ3 expression and promoting SVV replication. Interestingly, overexpression of Mfn2 also activated NLRP3 inflammasome but did not inhibit SVV proliferation. That may mean the RIG-I/IRF7 signaling pathway plays a more important role in SVV proliferation in PK-15 cells. This study could provide important insights into the modulation of host metabolism during SVV infection and provide a strong theoretical basis for a better understanding of the pathogenic mechanism and immune activation mechanism of SVV. Frontiers Media S.A. 2022-07-25 /pmc/articles/PMC9359100/ /pubmed/35958608 http://dx.doi.org/10.3389/fimmu.2022.955671 Text en Copyright © 2022 Deng, Zhu, Zhu, Sun, Ding, Li, Jian, Zhao, Deng, Deng, Deng, Guo, Sun, Lai, Tang, Cui, Ge and Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Deng, HuiDan
Zhu, Song
Zhu, Ling
Sun, Jing
Ding, YuChun
Li, FengQin
Jian, ZhiJie
Zhao, Jun
Deng, LiShuang
Deng, JunLiang
Deng, YouTian
Guo, HongRui
Sun, XianGang
Lai, Si Yuan
Tang, HuaQiao
Cui, HengMin
Ge, Liang Peng
Xu, ZhiWen
Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication
title Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication
title_full Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication
title_fullStr Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication
title_full_unstemmed Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication
title_short Mfn2 is responsible for inhibition of the RIG-I/IRF7 pathway and activation of NLRP3 inflammasome in Seneca Valley virus-infected PK-15 cells to promote viral replication
title_sort mfn2 is responsible for inhibition of the rig-i/irf7 pathway and activation of nlrp3 inflammasome in seneca valley virus-infected pk-15 cells to promote viral replication
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359100/
https://www.ncbi.nlm.nih.gov/pubmed/35958608
http://dx.doi.org/10.3389/fimmu.2022.955671
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