title: Janus effects of ADAR1 on CVB3-induced viral myocarditis at different infection stages.
abstract: BACKGROUND
  Coxsackievirus (CVB3) infection is the most common cause of viral myocarditis (VMC) characterized by viral infection and myocardial inflammation. ADAR1, the interferon (IFN)-inducible adenosine deaminase acting on RNA, has been reported to be functional in various viruses. Recent studies have demonstrated that ADAR1 holds an antiviral role or promotes viral replication depending on virus type.
  
  
  OBJECTIVE
  This study aims to investigate whether or not ADAR1 affects CVB3-induced VMC.
  
  
  METHODS
  We generated an acute VMC mouse model by CVB3 infection. ADAR1 expression was manipulated by in vivo polyethyleneimine-mediated ADAR1 up/down-regulation plasmid delivery.
  
  
  RESULTS
  Our study indicated that ADAR1 was up-regulated after CVB3 infection. ADAR1 down-regulation in the early stage of viral infection ameliorated CVB3-induced VMC. In this stage, viral replication was a key point to initiate inflammatory response. ADAR1 may affect inflammation mainly through viral replication as shown by the elevated IFN-β and decreased viral load with ADAR1 down-regulation. However, when the inflammatory response was established in the middle-late stage of viral infection, ADAR1 down-regulation aggravated disease progression. In this stage, Western blot analysis indicated that ADAR1 may directly influence inflammatory response through PKR and NF-κB signaling.
  
  
  CONCLUSIONS
  We demonstrated that ADAR1 exhibited double-edged effects during the early or middle-late stage of CVB3-induced VMC. Our findings may provide new insights into the therapeutic treatments of VMC.
authors: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China.
authors: Ning
authors: N
authors: Dong
authors: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China.
authors: Chunsheng
authors: C
authors: Dong
authors: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China. Electronic address: sdxiongfd@126.com.
authors: Sidong
authors: S
authors: Xiong
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D003384:Coxsackievirus Infections / Q000150:complications / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D016899:Interferon-beta / Q000378:metabolism*; D051379:Mice; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism / Q000821:virology; D015398:Signal Transduction / Q000502:physiology; D019562:Viral Load
chemical_list: D016899:Interferon-beta; C000599465:ADAR1 protein, mouse; D000243:Adenosine Deaminase
keywords: ADAR1; CVB3; Inflammatory response; Viral myocarditis