title: Enhancement of replication of RNA viruses by ADAR1 via RNA editing and inhibition of RNA-activated protein kinase.
abstract: Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA binding protein and RNA-editing enzyme that modifies cellular and viral RNAs, including coding and noncoding RNAs. This interferon (IFN)-induced protein was expected to have an antiviral role, but recent studies have demonstrated that it promotes the replication of many RNA viruses. The data from these experiments show that ADAR1 directly enhances replication of hepatitis delta virus, human immunodeficiency virus type 1, vesicular stomatitis virus, and measles virus. The proviral activity of ADAR1 occurs through two mechanisms: RNA editing and inhibition of RNA-activated protein kinase (PKR). While these pathways have been found independently, the two mechanisms can act in concert to increase viral replication and contribute to viral pathogenesis. This novel type of proviral regulation by an IFN-induced protein, combined with some antiviral effects of hyperediting, sheds new light on the importance of ADAR1 during viral infection and transforms our overall understanding of the innate immune response.
authors.affiliation: Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, 3999 Côte Ste. Catherine, Montréal, QC, H3T 1E2 Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gélinas
authors.forename: Guerline
authors.initials: G
authors.lastname: Clerzius
authors.forename: Eileen
authors.initials: E
authors.lastname: Shaw
authors.forename: Anne
authors.initials: A
authors.lastname: Gatignol
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D017393:RNA Editing; D012328:RNA Viruses / Q000502:physiology*; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors*
chemical_list: D012367:RNA, Viral; D016601:RNA-Binding Proteins; D019892:eIF-2 Kinase; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase