Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight

被引:12
|
作者
Cuervo, Natalia Zamorano [1 ]
Osseman, Quentin [1 ,2 ]
Grandvaux, Nathalie [1 ,2 ]
机构
[1] Univ Montreal, CRCHUM Ctr Hosp, 900 Rue St Denis, Montreal, PQ H2X 0A9, Canada
[2] Univ Montreal, Dept Biochem & Mol Med, Fac Med, Montreal, PQ H3C 3J7, Canada
来源
VIRUSES-BASEL | 2018年 / 10卷 / 02期
基金
加拿大健康研究院;
关键词
mitochondrial antiviral signaling (MAVS); virus; antiviral; interferon; pathogen recognition receptors (PRRs); oligomerization; aggregation; ANTIVIRAL INNATE IMMUNITY; HEPATITIS-C-VIRUS; RIG-I; SIGNALING PROTEIN; ADAPTER PROTEIN; AGGREGATION; PEROXISOMES; MECHANISMS; MEMBRANE; BINDING;
D O I
10.3390/v10020056
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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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页数:13
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