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RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2011 Jan 04; Vol. 108 (1), pp. 331-6. Date of Electronic Publication: 2010 Dec 20. - Publication Year :
- 2011
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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.
- Subjects :
- Animals
Antigens, CD metabolism
Cell Line
DNA Primers genetics
Fluorescent Antibody Technique
Gene Knockout Techniques
Green Fluorescent Proteins
Mice
Mice, Inbred C57BL
Protein Isoforms genetics
RNA-Binding Proteins
Receptors, Cell Surface metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signaling Lymphocytic Activation Molecule Family Member 1
Adenosine Deaminase genetics
Adenosine Deaminase metabolism
Embryonic Development genetics
Mutation genetics
SSPE Virus genetics
Subacute Sclerosing Panencephalitis genetics
Virus Replication genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 108
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 21173229
- Full Text :
- https://doi.org/10.1073/pnas.1017241108