title: HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG-I.
abstract: RIG-I is a key cytosolic sensor that detects RNA viruses through its C-terminal region and activates the production of antiviral interferons (IFNs) and proinflammatory cytokines. While posttranslational modification has been demonstrated to regulate RIG-I signaling activity, its significance for the sensing of viral RNAs remains unclear. Here, we first show that the RIG-I C-terminal region undergoes deacetylation to regulate its viral RNA-sensing activity and that the HDAC6-mediated deacetylation of RIG-I is critical for viral RNA detection. HDAC6 transiently bound to RIG-I and removed the lysine 909 acetylation in the presence of viral RNAs, promoting RIG-I sensing of viral RNAs. Depletion of HDAC6 expression led to impaired antiviral responses against RNA viruses, but not against DNA viruses. Consequently, HDAC6 knockout mice were highly susceptible to RNA virus infections compared to wild-type mice. These findings underscore the critical role of HDAC6 in the modulation of the RIG-I-mediated antiviral sensing pathway.
authors.affiliation: Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Korea.
authors.forename: Hyun-Cheol
authors.initials: HC
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, Korea.
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: College of Medicine, Inha University, Incheon, Korea.
authors.forename: Woon-Kyu
authors.initials: WK
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Korea.
authors.forename: Duk-Jae
authors.initials: DJ
authors.lastname: Jang
authors.affiliation: Foot and Mouth Disease Division, Animal Quarantine and Inspection Agency, Anyang, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Yoon
authors.affiliation: CKD Research Institute, Yongin-si Gyeonggi-do, Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Choi
authors.affiliation: CKD Research Institute, Yongin-si Gyeonggi-do, Korea.
authors.forename: Seihwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Korean Medicine (KM) Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: JinYeul
authors.initials: J
authors.lastname: Ma
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Korea.
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
authors.forename: Tso-Pang
authors.initials: TP
authors.lastname: Yao
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jae U
authors.initials: JU
authors.lastname: Jung
authors.affiliation: Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, Korea leejooyong@cnu.ac.kr jongsool@cnu.ac.kr.
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Korea leejooyong@cnu.ac.kr jongsool@cnu.ac.kr.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational; D012327:RNA Virus Infections / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology* / Q000378:metabolism*; D011971:Receptors, Immunologic
chemical_list: D012367:RNA, Viral; D011971:Receptors, Immunologic; C433811:HDAC6 protein, human; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: HDAC6; RIG‐I; deacetylation; innate immunity; virus sensing