AUTHOR=Liu Qiuju , Shao Qi , Xu Caixia , Liu Chao , Li Shuhan , Wang Jie , Liu Xia , Zhang Kehui , Yan Yaxian , Sun Jianhe , Cheng Yuqiang 

TITLE=Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in bats

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1574866

DOI=10.3389/fimmu.2025.1574866

ISSN=1664-3224

ABSTRACT=Bats exhibit unique abilities to coexist with viruses asymptomatically, setting them apart among mammals. The innate immune system serves as the primary defense against pathogens. As a crucial central node protein in this system, TANK binding kinase 1(TBK1) can receive signals from multiple pattern recognition receptors (PRRs), and then promote the production of Type I interferon (IFN I) and inflammatory factors. Despite its importance, how TBK1 works in bats remains poorly understood. Here, through bioinformatics analysis, TBK1 was found to exhibit a high sequence conservation across species. Overexpression of bat TBK1 significantly upregulated IFNβ expression, and then inhibited viral replication. Co-expression of bat TBK1 with bat IRF1/3/7 can facilitate the upregulation of IFNβ mediated by bat TBK1, implying the activation signals potentially can be transmitted from bat TBK1 to IRF1/3/7, and then promote IFNβ production. Structurally, protein kinase domain (PKD), ubiquitin-like domain (ULD), and coiled-coil domain 1 (CCD1) are essential domains for bat TBK1 to function normally. In summary, this study elucidated bat TBK1 has a conserved ability to activate bat antiviral innate immunity.