title: Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis.
abstract: BACKGROUND
  Honeysuckle (Lonicera japonica Thunb.), a traditional Chinese herb, has widely been used to treat pathogen infection. However, the underlying-mechanism remains elusive.
  
  
  OBJECTIVE
  To reveal the host microRNA (miRNA) profile with the anti-viral activity after honeysuckle treatment.
  
  
  METHODS
  Here we reveal the differentially expressed miRNAs by Solexa®deep sequencing from the blood of human and mice after the aqueous extract treatment. Among these overexpressed innate miRNAs both in human and mice, let-7a is able to target the NS1 region (nt 3313-3330) of dengue virus (DENV) serotypes 1, 2 and 4 predicated by the target predication software.
  
  
  RESULTS
  We confirmed that let-7a could target DENV2 at the predicated NS1 sequence and suppress DENV2 replication demonstrated by luciferase-reporter activity, RT-PCR, real-time PCR, Western blotting and plaque assay. ICR-suckling mice consumed honeysuckle aqueous extract either before or after intracranial injection with DENV2 showed decreased levels of NS1 RNA and protein expression accompanied with alleviated disease symptoms, decreased virus load, and prolonged survival time. Similar results were observed when DENV2-infected mice were intracranially injected with let-7a.
  
  
  CONCLUSIONS
  We reveal that honeysuckle attenuates DENV replication and related pathogenesis in vivo through induction of let-7a expression. This study opens a new direction for prevention and treatment of DENV infection through induction of the innate miRNA let-7a by honeysuckle.
authors.affiliation: Department of Medical Research, Chiayi Christian Hospital, Chiayi, Taiwan.
authors.forename: Ying-Ray
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Siao-Fen
authors.initials: SF
authors.lastname: Yeh
authors.affiliation: College of Biological Life Science, Nanjing University, Nanjing 210023, PR China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ruan
authors.affiliation: College of Biological Life Science, Nanjing University, Nanjing 210023, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Sheng-Da
authors.initials: SD
authors.lastname: Hsu
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; Molecular Bioinformatics Center, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Hsien-Da
authors.initials: HD
authors.lastname: Huang
authors.affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.
authors.forename: Chang-Chi
authors.initials: CC
authors.lastname: Hsieh
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Trai-Ming
authors.initials: TM
authors.lastname: Yeh
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. Electronic address: a713@mail.ncku.edu.tw.
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.affiliation: College of Biological Life Science, Nanjing University, Nanjing 210023, PR China. Electronic address: dr.gan1604@gmail.com.
authors.forename: Dai-Di
authors.initials: DD
authors.lastname: Gan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003716:Dengue Virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D031239:Lonicera; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D035683:MicroRNAs; D010936:Plant Extracts; C487931:mirnlet7 microRNA, human
keywords: Dengue virus replication; Honeysuckle; Let-7a