title: Viperin is induced following toll-like receptor 3 (TLR3) ligation and has a virus-responsive function in human trophoblast cells.
abstract: BACKGROUND
  Viperin, a virus-inducible antiviral protein, has been reported to inhibit the replication of a variety of viruses. However, its expression and function in trophoblast cells remains unclear. Toll-like receptor 3 (TLR3) is a key component of the innate immune system that recognizes viral double-stranded RNA and triggers immune reactions by producing type I interferon. We hypothesized that viperin inhibits the replication of human cytomegalovirus (HCMV) in trophoblast cells.
  
  
  METHODS
  In situ examinations of viperin expression was conducted in the human first-trimester placenta by immunohistochemical staining. Using a human trophoblast cell culture system, we studied the effect of TLR-3 ligation on viperin expression by treating trophoblasts with polyinosinic-polycytidylic acid [Poly (I: C)] (a synthetic double-stranded RNA, which mimics viral RNA). Viperin mRNA and protein expression were evaluated by real-time PCR and Western blot analysis. In a HCMV infected Swan 71 cell model, HCMV immediate early 1 (IE1) protein mRNA expression was evaluated by real-time PCR after viperin RNA interference.
  
  
  RESULTS
  Viperin was localized in trophoblast cells. Poly (I: C) induced viperin expression in a dosage and time-dependent manner. Blocking of TLR3 signaling by neutralizing antibody against IFN-β abolished the stimulation of viperin expression. After HCMV infection, expression of viperin mRNA and protein was unregulated. HCMV IE1 mRNA expression was significantly inhibited by viperin RNA interference.
  
  
  CONCLUSIONS
  Viperin is a virus-responsive protein that is constitutively expressed in human trophoblast cells. However, contrary to our hypothesis, viperin facilitates HCMV replication post infection.
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China. Electronic address: wangbo741003@163.com.
authors: B
authors: B
authors: Wang
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors: Y
authors: Y
authors: Fang
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors: Y
authors: Y
authors: Wu
authors: Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
authors: K
authors: K
authors: Koga
authors: Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
authors: Y
authors: Y
authors: Osuga
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors: S
authors: S
authors: Lv
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors: D
authors: D
authors: Chen
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors: Y
authors: Y
authors: Zhu
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors: J
authors: J
authors: Wang
authors: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors: H
authors: H
authors: Huang
mesh_terms: D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D000090123:Viperin Protein
chemical_list: D016899:Interferon-beta; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011070:Poly I-C; D011506:Proteins; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; C495344:TLR3 protein, human; C444427:RSAD2 protein, human; D000090123:Viperin Protein
keywords: Human cytomegalovirus; Toll-like receptor 3; Trophoblast; Viperin