Characterization of the Mollusc RIG-I/MAVS Pathway Reveals an Archaic Antiviral Signalling Framework in Invertebrates

Area of Science:

• Innate immunity
• Molecular biology
• Invertebrate zoology

Background:

• The RIG-I-like receptor (RLR) pathway, dependent on mitochondrial antiviral signalling protein (MAVS), is crucial for host antiviral immunity.
• Knowledge regarding the RLR pathway in invertebrates remains limited.

Purpose of the Study:

• To characterize the RLR pathway members in mollusks (oysters).
• To investigate the signal transduction mechanisms of the RLR pathway in oysters.
• To establish the MAVS-dependent RLR signaling pathway in invertebrates.

Main Methods:

• Gene expression analysis during viral challenge.
• In vitro poly(I:C) binding assays with oyster RIG-I-1.
• Protein-protein interaction studies (oyster RIG-I-1 with MAVS, MAVS with TRAF6).
• Analysis of MAVS self-association and NF-κB pathway activation.
• Functional assays of oyster IRFs in mammalian cells.

Main Results:

• Genes of the RLR pathway, including CgRIG-I-1, CgMAVS, CgTRAF6, and CgIRFs, were significantly induced during virus challenge.
• Oyster RIG-I-1 directly binds poly(I:C) and interacts with oyster MAVS.
• MAVS self-association is critical for signaling, and MAVS recruits TRAF6 to activate the NF-κB pathway.
• Oyster IRFs function downstream of MAVS and activate interferon promoter elements in mammalian cells.

Conclusions:

• This study establishes the MAVS-dependent RLR signaling pathway in invertebrates for the first time.
• The findings provide insights into invertebrate antiviral mechanisms.
• This research contributes to understanding the evolution of the vertebrate RLR network.