The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.
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-de...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-02-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010277&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850162828390957056 |
|---|---|
| author | Alice A Torres Stephanie L Macilwee Amir Rashid Sarah E Cox Jonas D Albarnaz Claudio A Bonjardim Geoffrey L Smith |
| author_facet | Alice A Torres Stephanie L Macilwee Amir Rashid Sarah E Cox Jonas D Albarnaz Claudio A Bonjardim Geoffrey L Smith |
| author_sort | Alice A Torres |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-132f8bb471a24281b14bd3fac53a0da1 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2022-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-132f8bb471a24281b14bd3fac53a0da12025-08-20T02:22:26ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-02-01182e101027710.1371/journal.ppat.1010277The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.Alice A TorresStephanie L MacilweeAmir RashidSarah E CoxJonas D AlbarnazClaudio A BonjardimGeoffrey L SmithCellular 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010277&type=printable |
| spellingShingle | Alice A Torres Stephanie L Macilwee Amir Rashid Sarah E Cox Jonas D Albarnaz Claudio A Bonjardim Geoffrey L Smith The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. PLoS Pathogens |
| title | The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. |
| title_full | The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. |
| title_fullStr | The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. |
| title_full_unstemmed | The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. |
| title_short | The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling. |
| title_sort | actin nucleator spir 1 is a virus restriction factor that promotes innate immune signalling |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010277&type=printable |
| work_keys_str_mv | AT aliceatorres theactinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT stephanielmacilwee theactinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT amirrashid theactinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT sarahecox theactinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT jonasdalbarnaz theactinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT claudioabonjardim theactinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT geoffreylsmith theactinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT aliceatorres actinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT stephanielmacilwee actinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT amirrashid actinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT sarahecox actinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT jonasdalbarnaz actinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT claudioabonjardim actinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling AT geoffreylsmith actinnucleatorspir1isavirusrestrictionfactorthatpromotesinnateimmunesignalling |