Bat Employs a Conserved MDA5 Gene to Trigger Antiviral Innate Immune Responses

Abstract

Bats are important hosts for various zoonotic viral diseases. However, they rarely show signs of disease infection with such viruses. As the first line for virus control, the innate immune system of bats attracted our full attention. In this study, the Tadarida brasiliensis MDA5 gene (batMDA5), a major sensor for anti-RNA viral infection, was first cloned, and its biological functions in antiviral innate immunity were identified. Bioinformatics analysis shows that the amino acid sequence of batMDA5 is poorly conserved among species, and it is evolutionarily closer to humans. The mRNA of batMDA5 was significantly upregulated in Newcastle disease virus (NDV), avian influenza virus (AIV), and vesicular stomatitis virus (VSV)-infected bat TB 1 Lu cells. Overexpression of batMDA5 could activate IFNβ and inhibit vesicular stomatitis virus (VSV-GFP) replication in TB 1 Lu cells, while knockdown of batMDA5 yielded the opposite result. In addition, we found that the CARD domain was essential for MDA5 to activate IFNβ by constructing MDA5 domain mutant plasmids. These results indicated that bat employs a conserved MDA5 gene to trigger anti-RNA virus innate immune response. This study helps understand the biological role of MDA5 in innate immunity during evolution.

Construction of a peacock immortalized fibroblast cell line for avian virus production

“…Avian influenza virus ( AIV ), the A/Chicken/Shanghai/010/2008 (H9N2) virus (SH010) isolated from chickens in shanghai, China, in 2008 and identified as H9N2 avian influenza A virus ( Cheng et al, 2015 ). The GFP-tagged vesicular stomatitis virus ( VSV ) VSV-GFP, was stored in our Laboratory ( Wang et al, 2022 ).…”

Conserved Function of Bat IRF7 in Activating Antiviral Innate Immunity Insights into the Innate Immune Response in Bats

“…The GFP tagged vesicular stomatitis virus (VSV) VSV-GFP were stored in our Laboratory. The viruses were puri ed, propagated, and stored as described in our previous study [20].…”

Genomic and biological variation in bat IFNs: An antiviral treatment approach

“…However, the IKK pathway activates the P50 protein which induces NFκB activation and consequently Type I IFN production 21,42–44 . Retinoic acid inducible gene I (RIG‐I) and RIG‐I‐like proteins such as the melanoma differentiation associated protein 5 (MDA5) are important nucleic acid binding proteins that are part of the pattern recognition receptor proteins (PRRs) 45,46 . MDA5 and RIG‐I bind to viral dsRNA post infection, this binding has been shown to induce the expression of Type I IFNs 47 .…”

“…It was also shown that the batMDA5 genomic sequence was conserved between bats, humans, horses, and pigs (homology among mammals), however MDA5 sequences showed lower homology between bat species (inter‐species differences and evolution) 45 . Although research shows that antiviral response is highly induced in bat cell lines, 45 the ability of carrying multiple replicating viruses and being asymptomatic is still a mystery 45,48 . This lead researchers to believe that MDA5 mildly induces Type I IFN expression as a response to viral infection 45 .…”

“…Although research shows that antiviral response is highly induced in bat cell lines, 45 the ability of carrying multiple replicating viruses and being asymptomatic is still a mystery 45,48 . This lead researchers to believe that MDA5 mildly induces Type I IFN expression as a response to viral infection 45 . Figure 2 illustrates the cellular detection mechanism of RNA viruses upon infection and the consequent activation of IFN response.…”