Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Chen, Ling, Ting, Zhong, Ni, Xu, Liang-Guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646042/
https://www.ncbi.nlm.nih.gov/pubmed/34880843
http://dx.doi.org/10.3389/fmicb.2021.770600
_version_ 1784610441244180480
author Wang, Chen
Ling, Ting
Zhong, Ni
Xu, Liang-Guo
author_facet Wang, Chen
Ling, Ting
Zhong, Ni
Xu, Liang-Guo
author_sort Wang, Chen
collection PubMed
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 Online
Article
Text
id pubmed-8646042
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86460422021-12-07 N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein Wang, Chen Ling, Ting Zhong, Ni Xu, Liang-Guo Front Microbiol Microbiology 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. Frontiers Media S.A. 2021-11-22 /pmc/articles/PMC8646042/ /pubmed/34880843 http://dx.doi.org/10.3389/fmicb.2021.770600 Text en Copyright © 2021 Wang, Ling, Zhong 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 Microbiology
Wang, Chen
Ling, Ting
Zhong, Ni
Xu, Liang-Guo
N4BP3 Regulates RIG-I-Like Receptor Antiviral Signaling Positively by Targeting Mitochondrial Antiviral Signaling Protein
title 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_short 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
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646042/
https://www.ncbi.nlm.nih.gov/pubmed/34880843
http://dx.doi.org/10.3389/fmicb.2021.770600
work_keys_str_mv AT wangchen n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein
AT lingting n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein
AT zhongni n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein
AT xuliangguo n4bp3regulatesrigilikereceptorantiviralsignalingpositivelybytargetingmitochondrialantiviralsignalingprotein