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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Qiuju Liu, Qi Shao, Caixia Xu, Chao Liu, Shuhan Li, Jie Wang, Xia Liu, Kehui Zhang, Yaxian Yan, Jianhe Sun, Yuqiang Cheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574866/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849730112129335296
author Qiuju Liu
Qi Shao
Caixia Xu
Chao Liu
Shuhan Li
Jie Wang
Xia Liu
Kehui Zhang
Yaxian Yan
Jianhe Sun
Yuqiang Cheng
author_facet Qiuju Liu
Qi Shao
Caixia Xu
Chao Liu
Shuhan Li
Jie Wang
Xia Liu
Kehui Zhang
Yaxian Yan
Jianhe Sun
Yuqiang Cheng
author_sort Qiuju Liu
collection DOAJ
description 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.
format Article
id doaj-art-51ddb2e00e374e41a298efb39bbe005e
institution DOAJ
issn 1664-3224
language English
publishDate 2025-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-51ddb2e00e374e41a298efb39bbe005e2025-08-20T03:08:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15748661574866Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in batsQiuju Liu0Qi Shao1Caixia Xu2Chao Liu3Shuhan Li4Jie Wang5Xia Liu6Kehui Zhang7Yaxian Yan8Jianhe Sun9Yuqiang Cheng10Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaKey Laboratory of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, ChinaShandong Provincial Key Laboratory of Zoonoses, Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, College of Veterinary Medicine, Shandong Agricultural University, Shandong, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, ChinaBats 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574866/fullBATTBK1virusinnate immunityIFNβ
spellingShingle Qiuju Liu
Qi Shao
Caixia Xu
Chao Liu
Shuhan Li
Jie Wang
Xia Liu
Kehui Zhang
Yaxian Yan
Jianhe Sun
Yuqiang Cheng
Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in bats
Frontiers in Immunology
BAT
TBK1
virus
innate immunity
IFNβ
title Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in bats
title_full Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in bats
title_fullStr Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in bats
title_full_unstemmed Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in bats
title_short Conserved function of bat TBK1 in activating innate immunity against RNA viruses: insights into the innate immune response in bats
title_sort conserved function of bat tbk1 in activating innate immunity against rna viruses insights into the innate immune response in bats
topic BAT
TBK1
virus
innate immunity
IFNβ
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574866/full
work_keys_str_mv AT qiujuliu conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT qishao conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT caixiaxu conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT chaoliu conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT shuhanli conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT jiewang conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT xialiu conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT kehuizhang conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT yaxianyan conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT jianhesun conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats
AT yuqiangcheng conservedfunctionofbattbk1inactivatinginnateimmunityagainstrnavirusesinsightsintotheinnateimmuneresponseinbats