Abstract
Despite the mitochondrial antiviral signalling protein (MAVS)-dependent RIG-I-like receptor (RLR) signalling pathway in the cytosol plays an indispensable role in the antiviral immunity of the host, surprising little is known in invertebrates. Here we characterized the major members of RLR pathway and investigated their signal transduction a Molluscs. We show that genes involved in RLR pathway were significantly induced during virus challenge, including CgRIG-I-1, CgMAVS, CgTRAF6 (TNF receptor-associated factor 6), and CgIRFs (interferon regulatory factors. Similar to human RIG-I, oyster RIG-I-1 could bind poly(I:C) directly in vitro and interact with oyster MAVS via its caspase activation and recruitment domains. We also show that transmembrane domain-dependent self-association of CgMAVS may be crucial for its signalling and that CgMAVS can recruit the downstream signalling molecule, TRAF6, which can subsequently activate NF-κB signal pathway. Moreover, oyster IRFs appeared to function downstream of CgMAVS and were able to activate the interferon β promoter and interferon stimulated response elements in mammalian cells. These results establish invertebrate MAVS-dependent RLR signalling for the first time and would be helpful for deciphering the antiviral mechanisms of invertebrates and understanding the development of the vertebrate RLR network.
Highlights
Among PRRs, the RIG-I like receptors (RLRs) detect viral RNA in the cytoplasm and induce the expression of IFNs6
Tumour necrosis factor (TNF) receptor-associated factor (TRAF) family members are involved in RLR signalling cascades downstream of MAVS18 and interaction between mitochondrial antiviral signalling (MAVS) and TRAF3 is essential for interferon regulatory factor (IRF) 3/7 activation and type I IFN production[19, 20], whereas interaction of MAVS with TRAF2/6 is likely responsible for NF-κB activation[14]
By analysing the transcriptome of oyster larvae infected with ostreid herpesvirus 1 (OsHV-1) at different developmental stages (Fig. 1A), we found that numerous genes in the RLR pathway were differentially regulated in response to viral challenge
Summary
The antiviral response of RLR pathway genes after virus infection of oyster larvae. By analysing the transcriptome of oyster larvae infected with OsHV-1 at different developmental stages (Fig. 1A), we found that numerous genes in the RLR pathway were differentially regulated in response to viral challenge. The expression of these genes in oyster larvae that developed normally and without a virus challenge did not exhibit the same upregulation or similar expression profiles (Supplementary Figs 1 and 2). Identification of key genes in the oyster RLR antiviral signalling pathway. Almost all of the key genes of the RLR signalling pathway have been predicted in the genome of the Pacific oyster[38]. To better understand the function of the oyster RLR signalling pathway, we first cloned a number of key oyster genes homologous to those encoding mammalian RLR antiviral signalling pathway proteins, including CgRIG-I-1 (Cg24392, GenBank Accession number: KY630188), CgMAVS (GenBank Accession number: KY630189), CgTRAF244 (Cg08964), CgTRAF345 (Cg23158), CgTRAF6 (Cg10206, GenBank Accession number: KY630190),
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