title: RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis.
abstract: Measles virus (MV), a member of the family Paramyxoviridae and an exclusively human pathogen, is among the most infectious viruses. A progressive fatal neurodegenerative complication, subacute sclerosing panencephalitis (SSPE), occurs during persistent MV infection of the CNS and is associated with biased hypermutations of the viral genome. The observed hypermutations of A-to-G are consistent with conversions catalyzed by the adenosine deaminase acting on RNA (ADAR1). To evaluate the role of ADAR1 in MV infection, we selectively disrupted expression of the IFN-inducible p150 ADAR1 isoform and found it caused embryonic lethality at embryo day (E) 11-E12. We therefore generated p150-deficient and WT mouse embryo fibroblast (MEF) cells stably expressing the MV receptor signaling lymphocyte activation molecule (SLAM or CD150). The p150(-/-) but not WT MEF cells displayed extensive syncytium formation and cytopathic effect (CPE) following infection with MV, consistent with an anti-MV role of the p150 isoform of ADAR1. MV titers were 3 to 4 log higher in p150(-/-) cells compared with WT cells at 21 h postinfection, and restoration of ADAR1 in p150(-/-) cells prevented MV cytopathology. In contrast to infection with MV, p150 disruption had no effect on vesicular stomatitis virus, reovirus, or lymphocytic choriomeningitis virus replication but protected against CPE resulting from infection with Newcastle disease virus, Sendai virus, canine distemper virus, and influenza A virus. Thus, ADAR1 is a restriction factor in the replication of paramyxoviruses and orthomyxoviruses.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Simone V
authors.initials: SV
authors.lastname: Ward
authors.forename: Cyril X
authors.initials: CX
authors.lastname: George
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liou
authors.forename: Bumsuk
authors.initials: B
authors.lastname: Hahm
authors.forename: Hanna
authors.initials: H
authors.lastname: Lewicki
authors.forename: Juan C
authors.initials: JC
authors.lastname: de la Torre
authors.forename: Charles E
authors.initials: CE
authors.lastname: Samuel
authors.forename: Michael B
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D055786:Gene Knockout Techniques; D049452:Green Fluorescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013190:SSPE Virus / Q000235:genetics*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013344:Subacute Sclerosing Panencephalitis / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D049452:Green Fluorescent Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase