Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways

Signal-regulatory protein alpha (SIRPA) is a well-known inhibitor of phagocytosis when it complexes with CD47 expressed on target cells. Here we show that SIRPA decreased in vitro infection by a number of pathogenic viruses, including New World and Old World arena-viruses, Zika virus, vesicular stom...

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Váldodahkki: Sarute, Nicolás (author)
Eará dahkkit: Cheng, Han (author), Yan, Zhonghao (author), Salas-Briceno, Karen (author), Richne, Justin (author), Rong, Lijun (author), Ross, S. R. (author)
Materiálatiipa: article
Giella:eaŋgalasgiella
Almmustuhtton: 2021
Fáttát:
Liŋkkat:https://hdl.handle.net/20.500.12008/38247
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author Sarute, Nicolás
author2 Cheng, Han
Yan, Zhonghao
Salas-Briceno, Karen
Richne, Justin
Rong, Lijun
Ross, S. R.
author2_role author
author
author
author
author
author
author_browse Cheng, Han
Richne, Justin
Rong, Lijun
Ross, S. R.
Salas-Briceno, Karen
Sarute, Nicolás
Yan, Zhonghao
author_facet Sarute, Nicolás
Cheng, Han
Yan, Zhonghao
Salas-Briceno, Karen
Richne, Justin
Rong, Lijun
Ross, S. R.
author_role author
collection COLIBRI
dc.contributor.none.fl_str_mv Sarute Nicolás, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.
Cheng Han, University of Illinois
Yan Zhonghao, University of Illinois
Salas-Briceno Karen, University of Illinois
Richne Justin, University of Illinois
Rong Lijun, University of Illinois
Ross S. R., University of Illinois
dc.creator.none.fl_str_mv Sarute, Nicolás
Cheng, Han
Yan, Zhonghao
Salas-Briceno, Karen
Richne, Justin
Rong, Lijun
Ross, S. R.
dc.date.none.fl_str_mv 2021
2023-07-20T15:08:04Z
2023-07-20T15:08:04Z
dc.format.none.fl_str_mv 23 h
application/pdf
dc.identifier.none.fl_str_mv Sarute, N, Cheng, H, Yan, Z, [y otros autores] "Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways". PLoS Pathog. [en línea] 2021, 17(6): e1009662. 23 h. DOI: 10.1371/journal.ppat.1009662
1553-7374
https://hdl.handle.net/20.500.12008/38247
10.1371/journal.ppat.1009662
dc.language.none.fl_str_mv en
eng
dc.publisher.none.fl_str_mv PloS ONE
dc.relation.none.fl_str_mv PLoS Pathog,2021, 17(6): e1009662.
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Licencia Creative Commons Atribución (CC - By 4.0)
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.none.fl_str_mv Vesicular stomatitis virus
Ebola virus
Small interfering RNA
Phagocytosis
SARS CoV 2
293T cells
Transfection
Machupo Virus
dc.title.none.fl_str_mv Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
dc.type.none.fl_str_mv Artículo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
description Signal-regulatory protein alpha (SIRPA) is a well-known inhibitor of phagocytosis when it complexes with CD47 expressed on target cells. Here we show that SIRPA decreased in vitro infection by a number of pathogenic viruses, including New World and Old World arena-viruses, Zika virus, vesicular stomatitis virus and pseudoviruses bearing the Machupo virus, Ebola virus and SARS-CoV-2 glycoproteins, but not HSV-1, MLV or mNoV. Moreover, mice with targeted mutation of the Sirpa gene that renders it non-functional were more suscepti ble to infection with the New World arenaviruses Junı´n virus vaccine strain Candid 1 and Tacaribe virus, but not MLV or mNoV. All SIRPA-inhibited viruses have in common the requirement for trafficking to a low pH endosomal compartment. This was clearly demonstrated with SARS-CoV-2 pseudovirus, which was only inhibited by SIRPA in cells in which it required trafficking to the endosome. Similar to its role in phagocytosis inhibition, SIRPA decreased virus internalization but not binding to cell surface receptors. We also found that increasing SIRPA levels via treatment with IL-4 led to even greater anti-viral activity. These data suggest that enhancing SIRPA’s activity could be a target for anti-viral therapies.
eu_rights_str_mv openAccess
format article
id anni_da85067a3da7fa3fef723cf6dfd5b3de
identifier_str_mv Sarute, N, Cheng, H, Yan, Z, [y otros autores] "Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways". PLoS Pathog. [en línea] 2021, 17(6): e1009662. 23 h. DOI: 10.1371/journal.ppat.1009662
1553-7374
10.1371/journal.ppat.1009662
instacron_str Universidad de la República
institution Universidad de la República
instname_str Universidad de la República
language eng
language_invalid_str_mv en
network_acronym_str anni
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oai_identifier_str oai:colibri.udelar.edu.uy:20.500.12008/38247
publishDate 2021
publishDateSort 2021
publisher.none.fl_str_mv PloS ONE
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rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathwaysSarute, NicolásCheng, HanYan, ZhonghaoSalas-Briceno, KarenRichne, JustinRong, LijunRoss, S. R.Vesicular stomatitis virusEbola virusSmall interfering RNAPhagocytosisSARS CoV 2293T cellsTransfectionMachupo VirusSignal-regulatory protein alpha (SIRPA) is a well-known inhibitor of phagocytosis when it complexes with CD47 expressed on target cells. Here we show that SIRPA decreased in vitro infection by a number of pathogenic viruses, including New World and Old World arena-viruses, Zika virus, vesicular stomatitis virus and pseudoviruses bearing the Machupo virus, Ebola virus and SARS-CoV-2 glycoproteins, but not HSV-1, MLV or mNoV. Moreover, mice with targeted mutation of the Sirpa gene that renders it non-functional were more suscepti ble to infection with the New World arenaviruses Junı´n virus vaccine strain Candid 1 and Tacaribe virus, but not MLV or mNoV. All SIRPA-inhibited viruses have in common the requirement for trafficking to a low pH endosomal compartment. This was clearly demonstrated with SARS-CoV-2 pseudovirus, which was only inhibited by SIRPA in cells in which it required trafficking to the endosome. Similar to its role in phagocytosis inhibition, SIRPA decreased virus internalization but not binding to cell surface receptors. We also found that increasing SIRPA levels via treatment with IL-4 led to even greater anti-viral activity. These data suggest that enhancing SIRPA’s activity could be a target for anti-viral therapies.PloS ONESarute Nicolás, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Cheng Han, University of IllinoisYan Zhonghao, University of IllinoisSalas-Briceno Karen, University of IllinoisRichne Justin, University of IllinoisRong Lijun, University of IllinoisRoss S. R., University of Illinois2023-07-20T15:08:04Z2023-07-20T15:08:04Z2021Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion23 happlication/pdfSarute, N, Cheng, H, Yan, Z, [y otros autores] "Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways". PLoS Pathog. [en línea] 2021, 17(6): e1009662. 23 h. DOI: 10.1371/journal.ppat.10096621553-7374https://hdl.handle.net/20.500.12008/3824710.1371/journal.ppat.1009662reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengPLoS Pathog,2021, 17(6): e1009662.Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/382472026-04-14T10:10:07Z
spellingShingle Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
Sarute, Nicolás
Vesicular stomatitis virus
Ebola virus
Small interfering RNA
Phagocytosis
SARS CoV 2
293T cells
Transfection
Machupo Virus
status_str publishedVersion
title Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
title_full Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
title_fullStr Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
title_full_unstemmed Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
title_short Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
title_sort Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways
topic Vesicular stomatitis virus
Ebola virus
Small interfering RNA
Phagocytosis
SARS CoV 2
293T cells
Transfection
Machupo Virus
url https://hdl.handle.net/20.500.12008/38247