The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.
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Authors
Bonjardim, Claudio A
Publication Date
2022-02-11Journal Title
PLoS Pathog
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Torres, A. A., Macilwee, S. L., Rashid, A., Cox, S. E., Albarnaz, J. D., Bonjardim, C. A., & Smith, G. (2022). The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.. PLoS Pathog https://doi.org/10.1371/journal.ppat.1010277
Abstract
Cellular proteins often have multiple and diverse functions. This is illustrated with protein Spir-1 that is an actin nucleator, but, as shown here, also functions to enhance innate immune signalling downstream of RNA sensing by RIG-I/MDA-5. In human and mouse cells lacking Spir-1, IRF3 and NF-κB-dependent gene activation is impaired, whereas Spir-1 overexpression enhanced IRF3 activation. Furthermore, the infectious virus titres and sizes of plaques formed by two viruses that are sensed by RIG-I, vaccinia virus (VACV) and Zika virus, are increased in Spir-1-/- cells. These observations demonstrate the biological importance of Spir-1 in the response to virus infection. Like cellular proteins, viral proteins also have multiple and diverse functions. Here, we also show that VACV virulence factor K7 binds directly to Spir-1 and that a diphenylalanine motif of Spir-1 is needed for this interaction and for Spir-1-mediated enhancement of IRF3 activation. Thus, Spir-1 is a new virus restriction factor and is targeted directly by an immunomodulatory viral protein that enhances virus virulence and diminishes the host antiviral responses.
Sponsorship
Wellcome Trust (090315/B/09/A)
Isaac Newton Trust (18.07i(j))
Wellcome Trust (090315/Z/09/Z)
Identifiers
External DOI: https://doi.org/10.1371/journal.ppat.1010277
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333535
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