In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 2 ( 2022-2-11), p. e1010277-
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 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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010277
DOI:
10.1371/journal.ppat.1010277.g001
DOI:
10.1371/journal.ppat.1010277.g002
DOI:
10.1371/journal.ppat.1010277.g003
DOI:
10.1371/journal.ppat.1010277.g004
DOI:
10.1371/journal.ppat.1010277.g005
DOI:
10.1371/journal.ppat.1010277.g006
DOI:
10.1371/journal.ppat.1010277.g007
DOI:
10.1371/journal.ppat.1010277.s001
DOI:
10.1371/journal.ppat.1010277.s002
DOI:
10.1371/journal.ppat.1010277.s003
DOI:
10.1371/journal.ppat.1010277.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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