Journal
CELL HOST & MICROBE
Volume 16, Issue 1, Pages 19-30Publisher
CELL PRESS
DOI: 10.1016/j.chom.2014.06.007
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Funding
- Armenise-Harvard Foundation
- William Milton Fund
- NIH [R01 AI087846, R21 AI097699, RR000168, R01 AI105063]
- German Research Foundation [FU 949/1-1]
- Dutch Organization for Scientific Research (NWO): ZonMW [9120812]
- NGI [40-41009-98-8057]
- NWO [917-46-367, 912-04-025]
- VICI [918.10.619]
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The cytosolic sensor MDA5 is crucial for antiviral innate immune defense against various RNA viruses including measles virus; as such, many viruses have evolved strategies to antagonize the antiviral activity of MDA5. Here, we show that measles virus escapes MDA5 detection by targeting the phosphatases PP1 alpha and PP1 gamma, which regulate MDA5 activity by removing an inhibitory phosphorylation mark. The V proteins of measles virus and the related paramyxovirus Nipah virus interact with PP1 alpha/gamma, preventing PP1-mediated dephosphorylation of MDA5 and thereby its activation. The PP1 interaction with the measles V protein is mediated by a conserved PP1-binding motif in the C-terminal region of the V protein. A recombinant measles virus expressing a mutant V protein deficient in PP1 binding is unable to antagonize MDA5 and is growth impaired due to its inability to suppress interferon induction. This identifies PP1 antagonism as a mechanism employed by paramyxoviruses for evading innate immune recognition.
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