title: Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection.
abstract: Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection. This migration is inhibited by RESV treatment and is mediated by induction of Sirt1 which leads to the retention of HMGB1 in the nucleus and consequently helps in the increased production of interferon-stimulated genes (ISGs). Nuclear HMGB1 was found to bind to the promoter region of the ISG and positively regulated the expression of ISG. The enhanced transcription of ISGs by nuclear HMGB1 thus contributes to the antiviral activity of RESV against DENV. To the best of our knowledge, this is the first report to demonstrate that RESV antagonizes DENV replication and that nuclear HMGB1 plays a role in regulating ISG production.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Institute of Graduate Studies, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nurhafiza
authors.initials: N
authors.lastname: Zainal
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Peng
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Cheng
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.|Departments of Microbiology &Immunology and Pediatrics, and Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Wan
authors.affiliation: Translational Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.|Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tzong-Shiann
authors.initials: TS
authors.lastname: Ho
authors.affiliation: Institute of Graduate Studies, University of Malaya, Kuala Lumpur, Malaysia.|Tropical Infectious Diseases Research and Education Centre (TIDREC), University of Malaya, Kuala Lumpur, Malaysia.|Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sazaly
authors.initials: S
authors.lastname: AbuBakar
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003715:Dengue / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D003716:Dengue Virus / Q000302:isolation & purification / Q000502:physiology; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D024243:HMGB1 Protein; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D034741:RNA, Small Interfering; D013267:Stilbenes; D016899:Interferon-beta; D056564:Sirtuin 1; D000077185:Resveratrol