RGD Reference Report - Janus effects of ADAR1 on CVB3-induced viral myocarditis at different infection stages. - Rat Genome Database

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Janus effects of ADAR1 on CVB3-induced viral myocarditis at different infection stages.

Authors: Dong, Ning  Dong, Chunsheng  Xiong, Sidong 
Citation: Dong N, etal., Int J Cardiol. 2016 Nov 15;223:898-905. doi: 10.1016/j.ijcard.2016.08.315. Epub 2016 Aug 22.
RGD ID: 125097517
Pubmed: (View Article at PubMed) PMID:27584568
DOI: Full-text: DOI:10.1016/j.ijcard.2016.08.315


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.
OBJECTIVES: 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.
CONCLUSION: 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.

Annotation

Disease Annotations    
Viral Myocarditis  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Adar  (adenosine deaminase, RNA-specific)

Genes (Mus musculus)
Adar  (adenosine deaminase, RNA-specific)

Genes (Homo sapiens)
ADAR  (adenosine deaminase RNA specific)


Additional Information