PMID- 27875274 OWN - NLM STAT- MEDLINE DCOM- 20170803 LR - 20201209 IS - 1477-9137 (Electronic) IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 129 IP - 24 DP - 2016 Dec 15 TI - SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5'UTR RNA. PG - 4534-4547 AB - 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 3D(pol) protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3D(pol), 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. CI - (c) 2016. Published by The Company of Biologists Ltd. FAU - Han, Yang AU - Han Y AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Wang, Lvyin AU - Wang L AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Cui, Jin AU - Cui J AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Song, Yu AU - Song Y AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Luo, Zhen AU - Luo Z AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Chen, Junbo AU - Chen J AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Xiong, Ying AU - Xiong Y AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Zhang, Qi AU - Zhang Q AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Liu, Fang AU - Liu F AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Ho, Wenzhe AU - Ho W AD - State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. FAU - Liu, Yingle AU - Liu Y AD - 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. FAU - Wu, Kailang AU - Wu K AUID- ORCID: 0000-0002-8326-2895 AD - 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. FAU - Wu, Jianguo AU - Wu J AD - 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. LA - eng PT - Journal Article DEP - 20161114 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (3' Untranslated Regions) RN - 0 (5' Untranslated Regions) RN - 0 (Internal Ribosome Entry Sites) RN - 0 (RNA, Viral) RN - 0 (Small Ubiquitin-Related Modifier Proteins) RN - EC 2.7.7.48 (RNA-Dependent RNA Polymerase) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - 3' Untranslated Regions/genetics MH - 5' Untranslated Regions/*genetics MH - Acetylation MH - Cell Line MH - Cell Nucleus MH - Enterovirus A, Human/*genetics/physiology MH - *Genome, Viral MH - Humans MH - Internal Ribosome Entry Sites MH - Models, Biological MH - Nucleic Acid Conformation MH - Protein Binding MH - *Protein Biosynthesis MH - RNA, Viral/*metabolism MH - RNA-Dependent RNA Polymerase/*metabolism MH - Sirtuin 1/*metabolism MH - Small Ubiquitin-Related Modifier Proteins/metabolism MH - Sumoylation MH - *Virus Replication PMC - PMC5201017 OTO - NOTNLM OT - Enterovirus 71 OT - HDAC OT - IRES OT - Replication OT - SIRT1 OT - Transcription OT - Translation OT - Viral infection COIS- The authors declare no competing or financial interests. EDAT- 2016/11/23 06:00 MHDA- 2017/08/05 06:00 PMCR- 2016/12/15 CRDT- 2016/11/23 06:00 PHST- 2016/06/17 00:00 [received] PHST- 2016/11/02 00:00 [accepted] PHST- 2016/11/23 06:00 [pubmed] PHST- 2017/08/05 06:00 [medline] PHST- 2016/11/23 06:00 [entrez] PHST- 2016/12/15 00:00 [pmc-release] AID - jcs.193698 [pii] AID - JCS193698 [pii] AID - 10.1242/jcs.193698 [doi] PST - ppublish SO - J Cell Sci. 2016 Dec 15;129(24):4534-4547. doi: 10.1242/jcs.193698. Epub 2016 Nov 14.