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Proc Natl Acad Sci USA. RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis
RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis (PNAS, abstract, edited)
[Source: Proc Natl Acad Sci USA, full text: <cite cite="http://www.pnas.org/content/108/1/331.short?rss=1">RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis ? PNAS</cite>. Abstract, edited.]
RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis
1. Simone V. Ward a,1, 2. Cyril X. George b,1, 3. Megan J. Welch a, 4. Li-Ying Liou a, 5. Bumsuk Hahm a,c, 6. Hanna Lewicki a, 7. Juan C. de la Torre a, 8. Charles E. Samuel b,d, and 9. Michael B. Oldstone a,2
Author Affiliations
1. a Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
2. b Department of Molecular, Cellular, and Developmental Biology and
3. d Biomolecular Sciences and Engineering Program, University of California, Santa Barbara, CA 92106; and
4. c Departments of Surgery and Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212
1. Contributed by Michael B. Oldstone, November 19, 2010 (sent for review October 13, 2010)
2. ↵1S.V.W. and C.X.G. contributed equally to this work.
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.
Footnotes
* 2 To whom correspondence should be addressed. E-mail: mbaobo@scripps.edu.
* Author contributions: S.V.W., C.E.S., and M.B.O. designed research; S.V.W., C.X.G., M.J.W., L.-Y.L., B.H., H.L., and J.C.d.l.T. performed research; S.V.W., C.X.G., L.-Y.L., B.H., J.C.d.l.T., C.E.S., and M.B.O. analyzed data; and S.V.W., C.E.S., and M.B.O. wrote the paper.
* The authors declare no conflict of interest.
* This article contains supporting information online at https://www.pnas.org/lookup/suppl/do...DCSupplemental.
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[Source: Proc Natl Acad Sci USA, full text: <cite cite="http://www.pnas.org/content/108/1/331.short?rss=1">RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis ? PNAS</cite>. Abstract, edited.]
RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis
1. Simone V. Ward a,1, 2. Cyril X. George b,1, 3. Megan J. Welch a, 4. Li-Ying Liou a, 5. Bumsuk Hahm a,c, 6. Hanna Lewicki a, 7. Juan C. de la Torre a, 8. Charles E. Samuel b,d, and 9. Michael B. Oldstone a,2
Author Affiliations
1. a Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
2. b Department of Molecular, Cellular, and Developmental Biology and
3. d Biomolecular Sciences and Engineering Program, University of California, Santa Barbara, CA 92106; and
4. c Departments of Surgery and Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212
1. Contributed by Michael B. Oldstone, November 19, 2010 (sent for review October 13, 2010)
2. ↵1S.V.W. and C.X.G. contributed equally to this work.
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.
Footnotes
* 2 To whom correspondence should be addressed. E-mail: mbaobo@scripps.edu.
* Author contributions: S.V.W., C.E.S., and M.B.O. designed research; S.V.W., C.X.G., M.J.W., L.-Y.L., B.H., H.L., and J.C.d.l.T. performed research; S.V.W., C.X.G., L.-Y.L., B.H., J.C.d.l.T., C.E.S., and M.B.O. analyzed data; and S.V.W., C.E.S., and M.B.O. wrote the paper.
* The authors declare no conflict of interest.
* This article contains supporting information online at https://www.pnas.org/lookup/suppl/do...DCSupplemental.
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