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Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight
The mitochondrial antiviral signaling (MAVS) adaptor protein is a central signaling hub required for cells to mount an antiviral response following virus sensing by retinoic acid-inducible gene I (RIG-I)-like receptors. MAVS localizes in the membrane of mitochondria and peroxisomes and in mitochondr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850363/ https://www.ncbi.nlm.nih.gov/pubmed/29385716 http://dx.doi.org/10.3390/v10020056 |
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author | Zamorano Cuervo, Natalia Osseman, Quentin Grandvaux, Nathalie |
author_facet | Zamorano Cuervo, Natalia Osseman, Quentin Grandvaux, Nathalie |
author_sort | Zamorano Cuervo, Natalia |
collection | PubMed |
description | The mitochondrial antiviral signaling (MAVS) adaptor protein is a central signaling hub required for cells to mount an antiviral response following virus sensing by retinoic acid-inducible gene I (RIG-I)-like receptors. MAVS localizes in the membrane of mitochondria and peroxisomes and in mitochondrial-associated endoplasmic reticulum membranes. Structural and functional studies have revealed that MAVS activity relies on the formation of functional high molecular weight prion-like aggregates. The formation of protein aggregates typically relies on a dynamic transition between oligomerization and aggregation states. The existence of intermediate state(s) of MAVS polymers, other than aggregates, has not yet been documented. Here, we used a combination of non-reducing SDS-PAGE and semi-denaturing detergent agarose gel electrophoresis (SDD-AGE) to resolve whole cell extract preparations to distinguish MAVS polymerization states. While SDD-AGE analysis of whole cell extracts revealed the formation of previously described high molecular weight prion-like aggregates upon constitutively active RIG-I ectopic expression and virus infection, non-reducing SDS-PAGE allowed us to demonstrate the induction of lower molecular weight oligomers. Cleavage of MAVS using the NS3/4A protease revealed that anchoring to intracellular membranes is required for the appropriate polymerization into active high molecular weight aggregates. Altogether, our data suggest that RIG-I-dependent MAVS activation involves the coexistence of MAVS polymers with distinct molecular weights. |
format | Online Article Text |
id | pubmed-5850363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58503632018-03-16 Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight Zamorano Cuervo, Natalia Osseman, Quentin Grandvaux, Nathalie Viruses Article The mitochondrial antiviral signaling (MAVS) adaptor protein is a central signaling hub required for cells to mount an antiviral response following virus sensing by retinoic acid-inducible gene I (RIG-I)-like receptors. MAVS localizes in the membrane of mitochondria and peroxisomes and in mitochondrial-associated endoplasmic reticulum membranes. Structural and functional studies have revealed that MAVS activity relies on the formation of functional high molecular weight prion-like aggregates. The formation of protein aggregates typically relies on a dynamic transition between oligomerization and aggregation states. The existence of intermediate state(s) of MAVS polymers, other than aggregates, has not yet been documented. Here, we used a combination of non-reducing SDS-PAGE and semi-denaturing detergent agarose gel electrophoresis (SDD-AGE) to resolve whole cell extract preparations to distinguish MAVS polymerization states. While SDD-AGE analysis of whole cell extracts revealed the formation of previously described high molecular weight prion-like aggregates upon constitutively active RIG-I ectopic expression and virus infection, non-reducing SDS-PAGE allowed us to demonstrate the induction of lower molecular weight oligomers. Cleavage of MAVS using the NS3/4A protease revealed that anchoring to intracellular membranes is required for the appropriate polymerization into active high molecular weight aggregates. Altogether, our data suggest that RIG-I-dependent MAVS activation involves the coexistence of MAVS polymers with distinct molecular weights. MDPI 2018-01-30 /pmc/articles/PMC5850363/ /pubmed/29385716 http://dx.doi.org/10.3390/v10020056 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zamorano Cuervo, Natalia Osseman, Quentin Grandvaux, Nathalie Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight |
title | Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight |
title_full | Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight |
title_fullStr | Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight |
title_full_unstemmed | Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight |
title_short | Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight |
title_sort | virus infection triggers mavs polymers of distinct molecular weight |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850363/ https://www.ncbi.nlm.nih.gov/pubmed/29385716 http://dx.doi.org/10.3390/v10020056 |
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