title: SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5'UTR RNA.
abstract: Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5' untranslated region (5'UTR) and a polyadenylated 3'UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from the nucleus to the cytoplasm. More interestingly, activated SIRT1 subsequently binds with the EV71 3Dpolprotein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3Dpol, resulting in the attenuation of viral genome replication. Moreover, SIRT1 interacts with the cloverleaf structure of the EV71 RNA 5'UTR to inhibit viral RNA transcription, and binds to the internal ribosome entry site (IRES) of the EV71 5'UTR to attenuate viral RNA translation. Thus, EV71 stimulates SIRT1 production and activity, which in turn represses EV71 genome replication by inhibiting viral polymerase, and attenuates EV71 RNA transcription and translation by interfering with viral RNA. These results uncover a new function of SIRT1 and reveal a new mechanism underlying the regulation of EV71 replication.
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Lvyin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China jwu@whu.edu.cn mvlwu@whu.edu.cn wukailang@whu.edu.cn.
authors.forename: Yingle
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China jwu@whu.edu.cn mvlwu@whu.edu.cn wukailang@whu.edu.cn.
authors.forename: Kailang
authors.identifier: 0000-0002-8326-2895
authors.initials: K
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China jwu@whu.edu.cn mvlwu@whu.edu.cn wukailang@whu.edu.cn.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics*; D000107:Acetylation; D002460:Cell Line; D002467:Cell Nucleus; D029821:Enterovirus A, Human / Q000235:genetics* / Q000502:physiology; D016679:Genome, Viral; D006801:Humans; D000067556:Internal Ribosome Entry Sites; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000067556:Internal Ribosome Entry Sites; D012367:RNA, Viral; D025841:Small Ubiquitin-Related Modifier Proteins; D012324:RNA-Dependent RNA Polymerase; D056564:Sirtuin 1
keywords: Enterovirus 71; HDAC; IRES; Replication; SIRT1; Transcription; Translation; Viral infection