PMID- 28733114 OWN - NLM STAT- MEDLINE DCOM- 20180418 LR - 20180418 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 145 DP - 2017 Sep TI - Targeting heat shock factor 1 as an antiviral strategy against dengue virus replication in vitro and in vivo. PG - 44-53 LID - S0166-3542(17)30092-X [pii] LID - 10.1016/j.antiviral.2017.07.008 [doi] AB - Fever onset is correlated with viremia in dengue virus (DENV) patients. Heat shock factor 1 (HSF1), a heat stress response host transcription factor, plays a crucial role in regulating multiple cellular functions, as well as the onset of infectious diseases. This study evaluated the role of HSF1 in DENV replication as a means of regulating DENV infection in vitro and in vivo. DENV infection activated HSF1 in both Ca(2+) and protein kinase A-dependent manners. Inhibiting HSF1 effectively reduced DENV replication, not only in THP-1 cells but also in primary human monocytes. Activated HSF1 contributed to DENV replication by upregulating autophagy-related protein (Atg) 7, as autophagy is crucial for virus replication. Heat stress also activated HSF1, which in turn facilitated DENV replication. Activated HSF1, the increased Atg7, and autophagic induction were founded in the DENV-infected brains and pharmacologically inhibiting HSF1 reduced autophagy, viral protein expression, neuropathy, and mortality. These results provide new insight into HSF1 as a novel host factor for DENV infection through its role in facilitating autophagy-regulated viral replication in the brains. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Tsai, Tsung-Ting AU - Tsai TT AD - Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. FAU - Chen, Chia-Ling AU - Chen CL AD - Translational Research Center, Taipei Medical University, Taipei 110, Taiwan. FAU - Tsai, Cheng-Chieh AU - Tsai CC AD - Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan. FAU - Lin, Chiou-Feng AU - Lin CF AD - Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. Electronic address: cflin2014@tmu.edu.tw. LA - eng PT - Journal Article DEP - 20170718 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antiviral Agents) RN - 0 (Heat Shock Transcription Factors) RN - 0 (Hsf1 protein, mouse) SB - IM MH - Animals MH - Antiviral Agents/*pharmacology/*therapeutic use MH - Autophagy MH - Cell Line MH - DNA Replication/drug effects MH - Dengue/drug therapy/virology MH - Dengue Virus/*drug effects/physiology MH - Heat Shock Transcription Factors/*antagonists & inhibitors/*physiology MH - Humans MH - Mice MH - Monocytes/drug effects/virology MH - Virus Replication/*drug effects OTO - NOTNLM OT - Autophagy OT - Dengue virus OT - HSF1 OT - Infection OT - Neuropathy OT - Replication EDAT- 2017/07/25 06:00 MHDA- 2018/04/19 06:00 CRDT- 2017/07/23 06:00 PHST- 2017/02/13 00:00 [received] PHST- 2017/07/12 00:00 [revised] PHST- 2017/07/13 00:00 [accepted] PHST- 2017/07/25 06:00 [pubmed] PHST- 2018/04/19 06:00 [medline] PHST- 2017/07/23 06:00 [entrez] AID - S0166-3542(17)30092-X [pii] AID - 10.1016/j.antiviral.2017.07.008 [doi] PST - ppublish SO - Antiviral Res. 2017 Sep;145:44-53. doi: 10.1016/j.antiviral.2017.07.008. Epub 2017 Jul 18.