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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...

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Autores principales: Zamorano Cuervo, Natalia, Osseman, Quentin, Grandvaux, Nathalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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.
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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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