Details

Autor(en) / Beteiligte

• Torres, Alice A
• Macilwee, Stephanie L
• Rashid, Amir
• Cox, Sarah E
• Albarnaz, Jonas D
• Bonjardim, Claudio A
• Smith, Geoffrey L
• Schulz, Thomas F.

Titel

The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling

Ist Teil von

• PLoS pathogens, 2022-02, Vol.18 (2), p.e1010277-e1010277

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.