N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein

Mitochondrial antiviral signaling protein (MAVS), an adaptor protein, is activated by RIG-I, which is critical for an effective innate immune response to infection by various RNA viruses. Viral infection causes the RIG-I-like receptor (RLR) to recognize pathogen-derived dsRNA and then becomes activa...

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Autores principales:	Chen Wang, Ting Ling, Ni Zhong, Liang-Guo Xu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	N4BP3 MAVS innate immunity RLR antiviral signaling TRAF2 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b66c624c2a144bfebd0e97fdd023aa25
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spelling	oai:doaj.org-article:b66c624c2a144bfebd0e97fdd023aa252021-11-22T07:17:41ZN4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein1664-302X10.3389/fmicb.2021.770600https://doaj.org/article/b66c624c2a144bfebd0e97fdd023aa252021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.770600/fullhttps://doaj.org/toc/1664-302XMitochondrial antiviral signaling protein (MAVS), an adaptor protein, is activated by RIG-I, which is critical for an effective innate immune response to infection by various RNA viruses. Viral infection causes the RIG-I-like receptor (RLR) to recognize pathogen-derived dsRNA and then becomes activated to promote prion-like aggregation and activation of MAVS. Subsequently, through the recruitment of TRAF proteins, MAVS activates two signaling pathways mediated by TBK1-IRF3 and IKK- NF-κb, respectively, and turns on type I interferon and proinflammatory cytokines. This study discovered that NEDD4 binding protein 3 (N4BP3) is a positive regulator of the RLR signaling pathway by targeting MAVS. Overexpression of N4BP3 promoted virus-induced activation of the interferon-β (IFN-β) promoter and interferon-stimulated response element (ISRE). Further experiments showed that knockdown or knockout N4BP3 impaired RIG-I-like receptor (RLR)-mediated innate immune response, induction of downstream antiviral genes, and cellular antiviral responses. We also detected that N4BP3 could accelerate the interaction between MAVS and TRAF2. Related experiments revealed that N4BP3 could facilitate the ubiquitination modification of MAVS. These findings suggest that N4BP3 is a critical component of the RIG-I-like receptor (RLR)-mediated innate immune response by targeting MAVS, which also provided insight into the mechanisms of innate antiviral responses.Chen WangTing LingNi ZhongLiang-Guo XuFrontiers Media S.A.articleN4BP3MAVSinnate immunityRLR antiviral signalingTRAF2MicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	N4BP3 MAVS innate immunity RLR antiviral signaling TRAF2 Microbiology QR1-502
spellingShingle	N4BP3 MAVS innate immunity RLR antiviral signaling TRAF2 Microbiology QR1-502 Chen Wang Ting Ling Ni Zhong Liang-Guo Xu N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
description	Mitochondrial antiviral signaling protein (MAVS), an adaptor protein, is activated by RIG-I, which is critical for an effective innate immune response to infection by various RNA viruses. Viral infection causes the RIG-I-like receptor (RLR) to recognize pathogen-derived dsRNA and then becomes activated to promote prion-like aggregation and activation of MAVS. Subsequently, through the recruitment of TRAF proteins, MAVS activates two signaling pathways mediated by TBK1-IRF3 and IKK- NF-κb, respectively, and turns on type I interferon and proinflammatory cytokines. This study discovered that NEDD4 binding protein 3 (N4BP3) is a positive regulator of the RLR signaling pathway by targeting MAVS. Overexpression of N4BP3 promoted virus-induced activation of the interferon-β (IFN-β) promoter and interferon-stimulated response element (ISRE). Further experiments showed that knockdown or knockout N4BP3 impaired RIG-I-like receptor (RLR)-mediated innate immune response, induction of downstream antiviral genes, and cellular antiviral responses. We also detected that N4BP3 could accelerate the interaction between MAVS and TRAF2. Related experiments revealed that N4BP3 could facilitate the ubiquitination modification of MAVS. These findings suggest that N4BP3 is a critical component of the RIG-I-like receptor (RLR)-mediated innate immune response by targeting MAVS, which also provided insight into the mechanisms of innate antiviral responses.
format	article
author	Chen Wang Ting Ling Ni Zhong Liang-Guo Xu
author_facet	Chen Wang Ting Ling Ni Zhong Liang-Guo Xu
author_sort	Chen Wang
title	N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
title_short	N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
title_full	N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
title_fullStr	N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
title_full_unstemmed	N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
title_sort	n4bp3 regulates rig-i-like receptor antiviral signaling positively by targeting mitochondrial antiviral signaling protein
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b66c624c2a144bfebd0e97fdd023aa25
work_keys_str_mv	AT chenwang n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein AT tingling n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein AT nizhong n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein AT liangguoxu n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein
_version_	1718417876847689728

N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein

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