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AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines

Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-sp...

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Autores principales: Zwernik, Samuel D., Adams, Beau H., Raymond, Daniel A., Warner, Catherine M., Kassam, Amin B., Rovin, Richard A., Akhtar, Parvez
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626839/
https://www.ncbi.nlm.nih.gov/pubmed/34901388
http://dx.doi.org/10.1016/j.omto.2021.11.001
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author Zwernik, Samuel D.
Adams, Beau H.
Raymond, Daniel A.
Warner, Catherine M.
Kassam, Amin B.
Rovin, Richard A.
Akhtar, Parvez
author_facet Zwernik, Samuel D.
Adams, Beau H.
Raymond, Daniel A.
Warner, Catherine M.
Kassam, Amin B.
Rovin, Richard A.
Akhtar, Parvez
author_sort Zwernik, Samuel D.
collection PubMed
description Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-specific manner. Interestingly, AXL is frequently overexpressed in GBM patients. Using commercially available GBM cell lines, we first show that cells expressing AXL are permissive for ZIKV infection, while cells that do not express AXL are not. Furthermore, inhibition of AXL kinase using R428 and antibody blockade of AXL receptor strongly attenuated virus entry in GBM cell lines. Additionally, CRISPR knockout of the AXL gene in GBM cell lines completely abolished ZIKV infection, significantly inhibited viral replication, and significantly reduced apoptosis compared with parental lines. Lastly, introduction of AXL receptor into non-expressing cell lines renders the cells susceptible to ZIKV infection. Together, these findings demonstrate that ZIKV entry into GBM cells in vitro is mediated by the AXL receptor and that following cell entry, productive infection is cytotoxic. Thus, ZIKV is a potential oncolytic virus for GBM.
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spelling pubmed-86268392021-12-09 AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines Zwernik, Samuel D. Adams, Beau H. Raymond, Daniel A. Warner, Catherine M. Kassam, Amin B. Rovin, Richard A. Akhtar, Parvez Mol Ther Oncolytics Original Article Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-specific manner. Interestingly, AXL is frequently overexpressed in GBM patients. Using commercially available GBM cell lines, we first show that cells expressing AXL are permissive for ZIKV infection, while cells that do not express AXL are not. Furthermore, inhibition of AXL kinase using R428 and antibody blockade of AXL receptor strongly attenuated virus entry in GBM cell lines. Additionally, CRISPR knockout of the AXL gene in GBM cell lines completely abolished ZIKV infection, significantly inhibited viral replication, and significantly reduced apoptosis compared with parental lines. Lastly, introduction of AXL receptor into non-expressing cell lines renders the cells susceptible to ZIKV infection. Together, these findings demonstrate that ZIKV entry into GBM cells in vitro is mediated by the AXL receptor and that following cell entry, productive infection is cytotoxic. Thus, ZIKV is a potential oncolytic virus for GBM. American Society of Gene & Cell Therapy 2021-11-11 /pmc/articles/PMC8626839/ /pubmed/34901388 http://dx.doi.org/10.1016/j.omto.2021.11.001 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Zwernik, Samuel D.
Adams, Beau H.
Raymond, Daniel A.
Warner, Catherine M.
Kassam, Amin B.
Rovin, Richard A.
Akhtar, Parvez
AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_full AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_fullStr AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_full_unstemmed AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_short AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_sort axl receptor is required for zika virus strain mr-766 infection in human glioblastoma cell lines
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626839/
https://www.ncbi.nlm.nih.gov/pubmed/34901388
http://dx.doi.org/10.1016/j.omto.2021.11.001
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