Regulation of MAVS Expression and Signaling Function in the Antiviral Innate Immune Response

Abstract

Viral infection is controlled by host innate immune cells that express specialized receptors for viral components. Engagement of these pattern recognition receptors triggers a series of signaling pathways that culminate in the production of antiviral mediators such as type I interferons. Mitochondrial antiviral-signaling protein (MAVS) acts as a central hub for signal transduction initiated by RIG-I-like receptors, which predominantly recognize viral RNA. MAVS expression and function are regulated by both post-transcriptional and post-translational mechanisms, of which ubiquitination and phosphorylation play the most important roles in modulating MAVS function. Increasing evidence indicates that viruses can escape the host antiviral response by interfering at multiple points in the MAVS signaling pathways, thereby maintaining viral survival and replication. This review summarizes recent studies on the mechanisms by which MAVS expression and signaling are normally regulated and on the various strategies employed by viruses to antagonize MAVS activity, which may provide new insights into the design of novel antiviral agents.

A SARS-CoV-2 – host proximity interactome

“…Tagged at either terminus, ORF9B recovered a number of outer mitochondrial membrane proteins, including TOMM70, a mitochondrial import receptor subunit shown to associate with ORF9B in three other studies 6,7,32 , and whose binding can be recapitulated in vitro by purified proteins 32 . ORF9B also recovers many peptides for MAVS, a protein required for innate immune defense against viruses (reviewed in 33 ) that we previously studied in the context of a BioID map of mitochondrial organization 34 . This is consistent with a recently confirmed role of ORF9B in the regulation of innate immunity 35 .…”

A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research

“…viral RNAs). PAMP-bound PRRs interact with MAVS, which activates the NF-kB and Type I interferon signaling pathways 29 . Many different viruses block the host antiviral response by interfering with MAVS signaling.…”

SARS-CoV-2 induces a unique mitochondrial transcriptome signature

“…18 MAVS expression typically decreases after RNA viral infection due to the rise of ROS. 19 MAVS is also regulated by calcium, ATP, cholesterol, ceramides, and phospholipids. 20 That SARS-CoV-2 does not affect MAVS expression suggests (1) SARS-CoV-2 may be capable of "hijacking" MAVS; (2) in the presence of SARS-CoV-2, MAVS is regulated differentially at the post-transcriptional or post-translational level; or (3) SARS-CoV-2 can propagate e ciently in the presence of unaltered MAVS expression, which could partially explain the muted antiviral response published previously.…”