The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.
Bonjardim, Claudio A
Public Library of Science (PLoS)
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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, 18 (2) https://doi.org/10.1371/journal.ppat.1010277
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 KO 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.
Wellcome Trust (090315/B/09/A)
Isaac Newton Trust (18.07i(j))
Wellcome Trust (090315/Z/09/Z)
External DOI: https://doi.org/10.1371/journal.ppat.1010277
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334996
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/